Pharmacy

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Micrograph showing MM

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that ixazomib (Ninlaro^TM) receive conditional marketing authorization.

The recommendation is for ixazomib in combination with lenalidomide and dexamethasone as a treatment for adults with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission (EC).

If the EC grants the authorization, ixazomib will be the first oral proteasome inhibitor approved for use across the European Economic Area.

Ixazomib is being developed by Takeda Pharmaceutical Company Limited.

Phase 3 trial

The CHMP’s positive opinion of ixazomib is based on results from the phase 3 TOURMALINE-MM1 trial, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. The incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

About conditional authorization

Conditional marketing authorization represents an expedited path for approval. The EC grants this type of authorization before pivotal registration studies are completed.

Conditional marketing authorization is granted to products whose benefits are thought to outweigh their risks, products that address unmet needs, and products that are expected to provide a significant public health benefit.

If ixazomib receives conditional marketing authorization, Takeda will be required to provide post-approval updates on safety and efficacy analyses for TOURMALINE-MM1 and some other ongoing studies to demonstrate the treatment’s long-term effects.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to Resimmune® (A-dmDT390-bisFv[UCHT1]) for the treatment of mycosis fungoides (MF).

Resimmune is an anti-CD3 immunotoxin that targets and transiently depletes a high percentage of malignant and normal T cells.

Researchers believe this high rate of T-cell depletion may “reset” a patient’s immune system, leading to immunomodulation. However, the safety and efficacy of Resimmune has not been established.

Resimmune is being developed by Angimmune LLC.

Resimmune research

The FDA’s fast track designation for Resimmune is based on results from a phase 1 trial, which were published in haematologica last year.

The trial included 25 patients with cutaneous T-cell lymphoma (CTCL)—17 with stage IB-IIB disease and 8 with stage III-IV disease. The patients received Resimmune at varying doses—between 2.5 µg/kg and 11.25 µg/kg.

Safety

Drug-related adverse events for the entire study cohort (n=30) included:

• Grade 2-3 AST/ALT elevations (n=6)
• Grade 2 chills (n=10)
• Grade 5 EBV infection (n=1)
• Grade 3 EBV/CMV infection (n=5)
• Grade 2 fever (n=6)
• Grade 5 heart failure (n=2)
• Grade 2-3 hypoalbuminemia (n=11)
• Grade 2 hypomagnesemia (n=1)
• Grade 3 hypophosphatemia (n=3)
• Grade 2-4 hypotension (n=3)
• Grade 4 hypoxia (n=1)
• Grade 4 liver failure (n=1)
• Grade 4 metabolic acidosis (n=1)
• Grade 3 supraventricular tachycardia (n=2)
• Grade 3-4 uremia (n=3)
• Grade 2-4 vascular leak syndrome (n=5).

Efficacy and phase 2

Nine of the CTCL patients (36%) responded to Resimmune, and 4 (16%) had complete responses (CRs). The duration of CR was more than 38 months for 1 patient, more than 60 months for another, and more than 72 months for 2 patients.

Of the 5 partial responses, 2 lasted 3 months, 1 lasted more than 3 months, 1 lasted more than 6 months, and the longest lasted 14 months.

The researchers said this trial revealed a subgroup of CTCL patients with a very high response rate.

When they excluded patients whose mSWAT scores never exceeded 50 and who never had lymph node involvement or stage III disease, the researchers were left with 9 patients. This subgroup had an overall response rate of 89% and a CR rate of 50% (at 6 months of follow-up).

“Results from our phase 1 trial demonstrated a particularly robust response among certain patients with early stage disease, and the randomized phase 2 trial is designed to further explore this potential therapeutic benefit,” said David Neville, MD, president and chief scientific officer of Angimmune.

The objective of this phase 2 trial is to document the incidence of CRs with Resimmune compared to oral vorinostat after a maximum of 12 months of treatment. The trial will enroll patients with stage IB/IIB MF with mSWAT < 50 who have never had lymphoid disease or a prior hematopoietic stem cell transplant.

About fast track designation

The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to Resimmune® (A-dmDT390-bisFv[UCHT1]) for the treatment of mycosis fungoides (MF).

Resimmune is an anti-CD3 immunotoxin that targets and transiently depletes a high percentage of malignant and normal T cells.

Researchers believe this high rate of T-cell depletion may “reset” a patient’s immune system, leading to immunomodulation. However, the safety and efficacy of Resimmune has not been established.

Resimmune is being developed by Angimmune LLC.

Resimmune research

The FDA’s fast track designation for Resimmune is based on results from a phase 1 trial, which were published in haematologica last year.

The trial included 25 patients with cutaneous T-cell lymphoma (CTCL)—17 with stage IB-IIB disease and 8 with stage III-IV disease. The patients received Resimmune at varying doses—between 2.5 µg/kg and 11.25 µg/kg.

Safety

Drug-related adverse events for the entire study cohort (n=30) included:

• Grade 2-3 AST/ALT elevations (n=6)
• Grade 2 chills (n=10)
• Grade 5 EBV infection (n=1)
• Grade 3 EBV/CMV infection (n=5)
• Grade 2 fever (n=6)
• Grade 5 heart failure (n=2)
• Grade 2-3 hypoalbuminemia (n=11)
• Grade 2 hypomagnesemia (n=1)
• Grade 3 hypophosphatemia (n=3)
• Grade 2-4 hypotension (n=3)
• Grade 4 hypoxia (n=1)
• Grade 4 liver failure (n=1)
• Grade 4 metabolic acidosis (n=1)
• Grade 3 supraventricular tachycardia (n=2)
• Grade 3-4 uremia (n=3)
• Grade 2-4 vascular leak syndrome (n=5).

Efficacy and phase 2

Nine of the CTCL patients (36%) responded to Resimmune, and 4 (16%) had complete responses (CRs). The duration of CR was more than 38 months for 1 patient, more than 60 months for another, and more than 72 months for 2 patients.

Of the 5 partial responses, 2 lasted 3 months, 1 lasted more than 3 months, 1 lasted more than 6 months, and the longest lasted 14 months.

The researchers said this trial revealed a subgroup of CTCL patients with a very high response rate.

When they excluded patients whose mSWAT scores never exceeded 50 and who never had lymph node involvement or stage III disease, the researchers were left with 9 patients. This subgroup had an overall response rate of 89% and a CR rate of 50% (at 6 months of follow-up).

“Results from our phase 1 trial demonstrated a particularly robust response among certain patients with early stage disease, and the randomized phase 2 trial is designed to further explore this potential therapeutic benefit,” said David Neville, MD, president and chief scientific officer of Angimmune.

The objective of this phase 2 trial is to document the incidence of CRs with Resimmune compared to oral vorinostat after a maximum of 12 months of treatment. The trial will enroll patients with stage IB/IIB MF with mSWAT < 50 who have never had lymphoid disease or a prior hematopoietic stem cell transplant.

About fast track designation

The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.

Micrograph showing

mycosis fungoides

The US Food and Drug Administration (FDA) has granted fast track designation to Resimmune® (A-dmDT390-bisFv[UCHT1]) for the treatment of mycosis fungoides (MF).

Resimmune is an anti-CD3 immunotoxin that targets and transiently depletes a high percentage of malignant and normal T cells.

Researchers believe this high rate of T-cell depletion may “reset” a patient’s immune system, leading to immunomodulation. However, the safety and efficacy of Resimmune has not been established.

Resimmune is being developed by Angimmune LLC.

Resimmune research

The FDA’s fast track designation for Resimmune is based on results from a phase 1 trial, which were published in haematologica last year.

The trial included 25 patients with cutaneous T-cell lymphoma (CTCL)—17 with stage IB-IIB disease and 8 with stage III-IV disease. The patients received Resimmune at varying doses—between 2.5 µg/kg and 11.25 µg/kg.

Safety

Drug-related adverse events for the entire study cohort (n=30) included:

• Grade 2-3 AST/ALT elevations (n=6)
• Grade 2 chills (n=10)
• Grade 5 EBV infection (n=1)
• Grade 3 EBV/CMV infection (n=5)
• Grade 2 fever (n=6)
• Grade 5 heart failure (n=2)
• Grade 2-3 hypoalbuminemia (n=11)
• Grade 2 hypomagnesemia (n=1)
• Grade 3 hypophosphatemia (n=3)
• Grade 2-4 hypotension (n=3)
• Grade 4 hypoxia (n=1)
• Grade 4 liver failure (n=1)
• Grade 4 metabolic acidosis (n=1)
• Grade 3 supraventricular tachycardia (n=2)
• Grade 3-4 uremia (n=3)
• Grade 2-4 vascular leak syndrome (n=5).

Efficacy and phase 2

Nine of the CTCL patients (36%) responded to Resimmune, and 4 (16%) had complete responses (CRs). The duration of CR was more than 38 months for 1 patient, more than 60 months for another, and more than 72 months for 2 patients.

Of the 5 partial responses, 2 lasted 3 months, 1 lasted more than 3 months, 1 lasted more than 6 months, and the longest lasted 14 months.

The researchers said this trial revealed a subgroup of CTCL patients with a very high response rate.

When they excluded patients whose mSWAT scores never exceeded 50 and who never had lymph node involvement or stage III disease, the researchers were left with 9 patients. This subgroup had an overall response rate of 89% and a CR rate of 50% (at 6 months of follow-up).

“Results from our phase 1 trial demonstrated a particularly robust response among certain patients with early stage disease, and the randomized phase 2 trial is designed to further explore this potential therapeutic benefit,” said David Neville, MD, president and chief scientific officer of Angimmune.

The objective of this phase 2 trial is to document the incidence of CRs with Resimmune compared to oral vorinostat after a maximum of 12 months of treatment. The trial will enroll patients with stage IB/IIB MF with mSWAT < 50 who have never had lymphoid disease or a prior hematopoietic stem cell transplant.

About fast track designation

The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to Coversin as a treatment for paroxysmal nocturnal hemoglobinuria (PNH).

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex).

Coversin is being developed by Akari Therapeutics.

In vitro experiments have shown that Coversin inhibits red blood cell lysis in PNH, and Coversin can achieve full complement inhibition in the blood of PNH patients who are resistant to eculizumab.

In a phase 1a trial of healthy volunteers, Coversin completely inhibited complement C5 activity within 12 hours of administration.

Akari Therapeutics is currently conducting a phase 1b study of Coversin in healthy volunteers and is enrolling patients with eculizumab-resistant PNH in a phase 2 trial.

The company has also been administering Coversin to a patient with eculizumab-resistant PNH. Thus far, Coversin has prevented hemolytic episodes and improved disease symptoms in this patient. The only drug-related adverse event has been occasional local and transient irritation at the injection site.

“We have continued to see complete complement inhibition and symptom control in a PNH patient with resistance to eculizumab, who has been self-administering subcutaneous Coversin for over 7 months,” said Gur Roshwalb, MD, CEO of Akari Therapeutics.

“We believe that Coversin, when approved, could provide important benefits for all patients with PNH.”

Coversin is also being studied in atypical hemolytic uremic syndrome and Guillain Barré syndrome.

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to Coversin as a treatment for paroxysmal nocturnal hemoglobinuria (PNH).

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex).

Coversin is being developed by Akari Therapeutics.

In vitro experiments have shown that Coversin inhibits red blood cell lysis in PNH, and Coversin can achieve full complement inhibition in the blood of PNH patients who are resistant to eculizumab.

In a phase 1a trial of healthy volunteers, Coversin completely inhibited complement C5 activity within 12 hours of administration.

Akari Therapeutics is currently conducting a phase 1b study of Coversin in healthy volunteers and is enrolling patients with eculizumab-resistant PNH in a phase 2 trial.

The company has also been administering Coversin to a patient with eculizumab-resistant PNH. Thus far, Coversin has prevented hemolytic episodes and improved disease symptoms in this patient. The only drug-related adverse event has been occasional local and transient irritation at the injection site.

“We have continued to see complete complement inhibition and symptom control in a PNH patient with resistance to eculizumab, who has been self-administering subcutaneous Coversin for over 7 months,” said Gur Roshwalb, MD, CEO of Akari Therapeutics.

“We believe that Coversin, when approved, could provide important benefits for all patients with PNH.”

Coversin is also being studied in atypical hemolytic uremic syndrome and Guillain Barré syndrome.

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Red blood cells

The US Food and Drug Administration (FDA) has granted orphan drug designation to Coversin as a treatment for paroxysmal nocturnal hemoglobinuria (PNH).

Coversin is a recombinant small protein (16,740 Da) derived from a native protein found in the saliva of the Ornithodoros moubata tick.

The drug is a second-generation complement inhibitor that acts on complement component C5, preventing release of C5a and formation of C5b-9 (also known as the membrane attack complex).

Coversin is being developed by Akari Therapeutics.

In vitro experiments have shown that Coversin inhibits red blood cell lysis in PNH, and Coversin can achieve full complement inhibition in the blood of PNH patients who are resistant to eculizumab.

In a phase 1a trial of healthy volunteers, Coversin completely inhibited complement C5 activity within 12 hours of administration.

Akari Therapeutics is currently conducting a phase 1b study of Coversin in healthy volunteers and is enrolling patients with eculizumab-resistant PNH in a phase 2 trial.

The company has also been administering Coversin to a patient with eculizumab-resistant PNH. Thus far, Coversin has prevented hemolytic episodes and improved disease symptoms in this patient. The only drug-related adverse event has been occasional local and transient irritation at the injection site.

“We have continued to see complete complement inhibition and symptom control in a PNH patient with resistance to eculizumab, who has been self-administering subcutaneous Coversin for over 7 months,” said Gur Roshwalb, MD, CEO of Akari Therapeutics.

“We believe that Coversin, when approved, could provide important benefits for all patients with PNH.”

Coversin is also being studied in atypical hemolytic uremic syndrome and Guillain Barré syndrome.

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto®) to treat pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

The approval is based on results from a phase 1/2 study.

Continued approval of blinatumomab for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, blinatumomab received accelerated approval from the FDA to treat adults with Ph- relapsed or refractory BCP-ALL. The FDA has also granted the drug priority review, breakthrough therapy designation, and orphan drug designation.

Blinatumomab is being developed by Amgen. Full prescribing information is available at www.blincyto.com.

‘205 trial

The latest accelerated approval of blinatumomab is based on results from the phase 1/2 ‘205 trial, in which researchers evaluated blinatumomab in 93 pediatric patients with relapsed or refractory BCP-ALL.

Amgen said treatment in this study has been completed, subjects are being monitored for long-term efficacy, and the data will be submitted for publication.

Initial results from this study were presented at ASH 2014. The abstract included data on 39 patients with relapsed/refractory BCP-ALL and a median age of 9 (range, 2-16).

The patients received blinatumomab at a dose of 5-15 µg/m²/day. Nineteen patients completed 1 cycle of blinatumomab, 4 completed 2 cycles, and 2 completed 3 cycles.

During the first 2 treatment cycles, 12 patients achieved a complete response, 5 of whom were negative for minimal residual disease.

Six of the complete responders went on to transplant. The median relapse-free survival for complete responders was 5.6 months.

At 6 months of follow-up, the median overall survival for all 39 patients was 4.3 months.

All of the patients experienced adverse events. The most common were pyrexia (74%), anemia (33%), nausea (31%), headache (28%), hypertension (26%), increased alanine aminotransferase (23%), and cough (21%).

The most common grade 3 or higher events were anemia (26%), pyrexia (21%), increased alanine aminotransferase (18%), increased aspartate aminotransferase (18%), and febrile neutropenia (15%).

Three patients developed cytokine release syndrome (2 grade 3).

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto®) to treat pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

The approval is based on results from a phase 1/2 study.

Continued approval of blinatumomab for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, blinatumomab received accelerated approval from the FDA to treat adults with Ph- relapsed or refractory BCP-ALL. The FDA has also granted the drug priority review, breakthrough therapy designation, and orphan drug designation.

Blinatumomab is being developed by Amgen. Full prescribing information is available at www.blincyto.com.

‘205 trial

The latest accelerated approval of blinatumomab is based on results from the phase 1/2 ‘205 trial, in which researchers evaluated blinatumomab in 93 pediatric patients with relapsed or refractory BCP-ALL.

Amgen said treatment in this study has been completed, subjects are being monitored for long-term efficacy, and the data will be submitted for publication.

Initial results from this study were presented at ASH 2014. The abstract included data on 39 patients with relapsed/refractory BCP-ALL and a median age of 9 (range, 2-16).

The patients received blinatumomab at a dose of 5-15 µg/m²/day. Nineteen patients completed 1 cycle of blinatumomab, 4 completed 2 cycles, and 2 completed 3 cycles.

During the first 2 treatment cycles, 12 patients achieved a complete response, 5 of whom were negative for minimal residual disease.

Six of the complete responders went on to transplant. The median relapse-free survival for complete responders was 5.6 months.

At 6 months of follow-up, the median overall survival for all 39 patients was 4.3 months.

All of the patients experienced adverse events. The most common were pyrexia (74%), anemia (33%), nausea (31%), headache (28%), hypertension (26%), increased alanine aminotransferase (23%), and cough (21%).

The most common grade 3 or higher events were anemia (26%), pyrexia (21%), increased alanine aminotransferase (18%), increased aspartate aminotransferase (18%), and febrile neutropenia (15%).

Three patients developed cytokine release syndrome (2 grade 3).

Vials of blinatumomab powder

and solution for infusion

Photo courtesy of Amgen

The US Food and Drug Administration (FDA) has granted accelerated approval for blinatumomab (Blincyto®) to treat pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

The approval is based on results from a phase 1/2 study.

Continued approval of blinatumomab for this indication may be contingent upon verification of clinical benefit in subsequent trials.

Blinatumomab is a bispecific, CD19-directed, CD3 T-cell engager (BiTE®) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

In 2014, blinatumomab received accelerated approval from the FDA to treat adults with Ph- relapsed or refractory BCP-ALL. The FDA has also granted the drug priority review, breakthrough therapy designation, and orphan drug designation.

Blinatumomab is being developed by Amgen. Full prescribing information is available at www.blincyto.com.

‘205 trial

The latest accelerated approval of blinatumomab is based on results from the phase 1/2 ‘205 trial, in which researchers evaluated blinatumomab in 93 pediatric patients with relapsed or refractory BCP-ALL.

Amgen said treatment in this study has been completed, subjects are being monitored for long-term efficacy, and the data will be submitted for publication.

Initial results from this study were presented at ASH 2014. The abstract included data on 39 patients with relapsed/refractory BCP-ALL and a median age of 9 (range, 2-16).

The patients received blinatumomab at a dose of 5-15 µg/m²/day. Nineteen patients completed 1 cycle of blinatumomab, 4 completed 2 cycles, and 2 completed 3 cycles.

During the first 2 treatment cycles, 12 patients achieved a complete response, 5 of whom were negative for minimal residual disease.

Six of the complete responders went on to transplant. The median relapse-free survival for complete responders was 5.6 months.

At 6 months of follow-up, the median overall survival for all 39 patients was 4.3 months.

All of the patients experienced adverse events. The most common were pyrexia (74%), anemia (33%), nausea (31%), headache (28%), hypertension (26%), increased alanine aminotransferase (23%), and cough (21%).

The most common grade 3 or higher events were anemia (26%), pyrexia (21%), increased alanine aminotransferase (18%), increased aspartate aminotransferase (18%), and febrile neutropenia (15%).

Three patients developed cytokine release syndrome (2 grade 3).

Ofatumumab (Arzerra)

Photo courtesy of GSK

The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).

Ofatumumab was previously approved by the FDA for use in combination with chlorambucil to treat previously untreated CLL patients who cannot receive fludarabine-based therapy, as monotherapy for CLL that is refractory to fludarabine and alemtuzumab, and as maintenance therapy for patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.

Ofatumumab is a monoclonal antibody designed to target CD20.

The drug’s prescribing information includes a boxed warning noting that hepatitis B virus reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab. In some cases, this results in fulminant hepatitis, hepatic failure, and death.

The boxed warning also states that progressive multifocal leukoencephalopathy, resulting in death, can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

COMPLEMENT 2 trial

The FDA’s latest approval for ofatumumab is based on results of the phase 3 COMPLEMENT 2 trial. Novartis reported top-line results from this study in April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Ofatumumab (Arzerra)

Photo courtesy of GSK

The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).

Ofatumumab was previously approved by the FDA for use in combination with chlorambucil to treat previously untreated CLL patients who cannot receive fludarabine-based therapy, as monotherapy for CLL that is refractory to fludarabine and alemtuzumab, and as maintenance therapy for patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.

Ofatumumab is a monoclonal antibody designed to target CD20.

The drug’s prescribing information includes a boxed warning noting that hepatitis B virus reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab. In some cases, this results in fulminant hepatitis, hepatic failure, and death.

The boxed warning also states that progressive multifocal leukoencephalopathy, resulting in death, can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

COMPLEMENT 2 trial

The FDA’s latest approval for ofatumumab is based on results of the phase 3 COMPLEMENT 2 trial. Novartis reported top-line results from this study in April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Ofatumumab (Arzerra)

Photo courtesy of GSK

The US Food and Drug Administration (FDA) has approved the use of ofatumumab (Arzerra®) in combination with fludarabine and cyclophosphamide to treat patients with relapsed chronic lymphocytic leukemia (CLL).

Ofatumumab was previously approved by the FDA for use in combination with chlorambucil to treat previously untreated CLL patients who cannot receive fludarabine-based therapy, as monotherapy for CLL that is refractory to fludarabine and alemtuzumab, and as maintenance therapy for patients who are in complete or partial response after receiving at least 2 lines of therapy for recurrent or progressive CLL.

Ofatumumab is a monoclonal antibody designed to target CD20.

The drug’s prescribing information includes a boxed warning noting that hepatitis B virus reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab. In some cases, this results in fulminant hepatitis, hepatic failure, and death.

The boxed warning also states that progressive multifocal leukoencephalopathy, resulting in death, can occur in patients receiving CD20-directed cytolytic antibodies, including ofatumumab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

COMPLEMENT 2 trial

The FDA’s latest approval for ofatumumab is based on results of the phase 3 COMPLEMENT 2 trial. Novartis reported top-line results from this study in April.

The trial enrolled 365 patients with relapsed CLL. The patients were randomized 1:1 to receive up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide or up to 6 cycles of fludarabine and cyclophosphamide alone.

The primary endpoint was progression-free survival, as assessed by an independent review committee.

The median progression-free survival was 28.9 months for patients receiving ofatumumab plus fludarabine and cyclophosphamide, compared to 18.8 months for patients receiving fludarabine and cyclophosphamide alone (hazard ratio=0.67, P=0.0032).

Novartis said the safety profile observed in this study was consistent with other trials of ofatumumab, and no new safety signals were observed.

Micrograph showing CML

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending that bosutinib (Bosulif), a tyrosine kinase inhibitor used to treat certain patients with chronic myeloid leukemia (CML), be made available through the National Health Service (NHS).

This means patients will no longer have to apply to the Cancer Drugs Fund (CDF) to obtain bosutinib.

The CDF is money the government sets aside to pay for cancer drugs that haven’t been approved by NICE and aren’t available within the NHS in England.

Following the decision to reform the CDF earlier this year, NICE began to reappraise all drugs currently in the CDF in April. Bosutinib is the first drug to be looked at through this reconsideration process.

NICE previously considered making bosutinib available through the NHS in 2013 but decided the drug was not cost-effective. So bosutinib was made available to patients via the CDF.

As part of the reappraisal process, Pfizer offered a discount for bosutinib. Taking this discount into consideration, as well as the limited treatment options for CML patients, NICE decided bosutinib is cost-effective.

Bosutinib has conditional approval from the European Commission to treat adults with Philadelphia-chromosome-positive CML in chronic phase, accelerated phase, or blast phase, but only if those patients have previously received one or more tyrosine kinase inhibitors and are not considered eligible for treatment with imatinib, nilotinib, or dasatinib.

Micrograph showing CML

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending that bosutinib (Bosulif), a tyrosine kinase inhibitor used to treat certain patients with chronic myeloid leukemia (CML), be made available through the National Health Service (NHS).

This means patients will no longer have to apply to the Cancer Drugs Fund (CDF) to obtain bosutinib.

The CDF is money the government sets aside to pay for cancer drugs that haven’t been approved by NICE and aren’t available within the NHS in England.

Following the decision to reform the CDF earlier this year, NICE began to reappraise all drugs currently in the CDF in April. Bosutinib is the first drug to be looked at through this reconsideration process.

NICE previously considered making bosutinib available through the NHS in 2013 but decided the drug was not cost-effective. So bosutinib was made available to patients via the CDF.

As part of the reappraisal process, Pfizer offered a discount for bosutinib. Taking this discount into consideration, as well as the limited treatment options for CML patients, NICE decided bosutinib is cost-effective.

Bosutinib has conditional approval from the European Commission to treat adults with Philadelphia-chromosome-positive CML in chronic phase, accelerated phase, or blast phase, but only if those patients have previously received one or more tyrosine kinase inhibitors and are not considered eligible for treatment with imatinib, nilotinib, or dasatinib.

Micrograph showing CML

The National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending that bosutinib (Bosulif), a tyrosine kinase inhibitor used to treat certain patients with chronic myeloid leukemia (CML), be made available through the National Health Service (NHS).

This means patients will no longer have to apply to the Cancer Drugs Fund (CDF) to obtain bosutinib.

The CDF is money the government sets aside to pay for cancer drugs that haven’t been approved by NICE and aren’t available within the NHS in England.

Following the decision to reform the CDF earlier this year, NICE began to reappraise all drugs currently in the CDF in April. Bosutinib is the first drug to be looked at through this reconsideration process.

NICE previously considered making bosutinib available through the NHS in 2013 but decided the drug was not cost-effective. So bosutinib was made available to patients via the CDF.

As part of the reappraisal process, Pfizer offered a discount for bosutinib. Taking this discount into consideration, as well as the limited treatment options for CML patients, NICE decided bosutinib is cost-effective.

Bosutinib has conditional approval from the European Commission to treat adults with Philadelphia-chromosome-positive CML in chronic phase, accelerated phase, or blast phase, but only if those patients have previously received one or more tyrosine kinase inhibitors and are not considered eligible for treatment with imatinib, nilotinib, or dasatinib.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation to the PI3K delta inhibitor TGR-1202 for the treatment of chronic lymphocytic leukemia (CLL).

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases.

This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the drug is approved.

About TGR-1202

TG Therapeutics, Inc. is developing TGR-1202 as a treatment for hematologic malignancies.

The drug is currently being evaluated in the phase 3 UNITY-CLL trial (NCT02612311), which includes patients with previously treated and untreated CLL. Patients are receiving TGR-1202 plus ublituximab, obinutuzumab plus chlorambucil, ublituximab alone, or TGR-1202 alone.

At EHA 2016, researchers reported preliminary results of a phase 1/1b study (NCT02268851) of TGR-1202 in combination with ibrutinib in patients with relapsed/refractory CLL or mantle cell lymphoma.

At ASCO 2016, researchers reported long-term follow-up of 2 studies of TGR-1202.

The first (TGR-1202-101, NCT01767766) is a phase 1 study of TGR-1202 in patients with relapsed or refractory hematologic malignancies.

The second (UTX-TGR-103, NCT02006485) is a phase 1/1b trial evaluating the combination of ublituximab and TGR-1202 in patients with relapsed or refractory non-Hodgkin lymphoma or CLL.

At ASH 2015, researchers reported results of a phase 1 trial (TGR-GA-106, NCT02100852) of TGR-1202 in combination with obinutuzumab and chlorambucil in patients with CLL.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation to the PI3K delta inhibitor TGR-1202 for the treatment of chronic lymphocytic leukemia (CLL).

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases.

This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the drug is approved.

About TGR-1202

TG Therapeutics, Inc. is developing TGR-1202 as a treatment for hematologic malignancies.

The drug is currently being evaluated in the phase 3 UNITY-CLL trial (NCT02612311), which includes patients with previously treated and untreated CLL. Patients are receiving TGR-1202 plus ublituximab, obinutuzumab plus chlorambucil, ublituximab alone, or TGR-1202 alone.

At EHA 2016, researchers reported preliminary results of a phase 1/1b study (NCT02268851) of TGR-1202 in combination with ibrutinib in patients with relapsed/refractory CLL or mantle cell lymphoma.

At ASCO 2016, researchers reported long-term follow-up of 2 studies of TGR-1202.

The first (TGR-1202-101, NCT01767766) is a phase 1 study of TGR-1202 in patients with relapsed or refractory hematologic malignancies.

The second (UTX-TGR-103, NCT02006485) is a phase 1/1b trial evaluating the combination of ublituximab and TGR-1202 in patients with relapsed or refractory non-Hodgkin lymphoma or CLL.

At ASH 2015, researchers reported results of a phase 1 trial (TGR-GA-106, NCT02100852) of TGR-1202 in combination with obinutuzumab and chlorambucil in patients with CLL.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation to the PI3K delta inhibitor TGR-1202 for the treatment of chronic lymphocytic leukemia (CLL).

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases.

This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the drug is approved.

About TGR-1202

TG Therapeutics, Inc. is developing TGR-1202 as a treatment for hematologic malignancies.

The drug is currently being evaluated in the phase 3 UNITY-CLL trial (NCT02612311), which includes patients with previously treated and untreated CLL. Patients are receiving TGR-1202 plus ublituximab, obinutuzumab plus chlorambucil, ublituximab alone, or TGR-1202 alone.

At EHA 2016, researchers reported preliminary results of a phase 1/1b study (NCT02268851) of TGR-1202 in combination with ibrutinib in patients with relapsed/refractory CLL or mantle cell lymphoma.

At ASCO 2016, researchers reported long-term follow-up of 2 studies of TGR-1202.

The first (TGR-1202-101, NCT01767766) is a phase 1 study of TGR-1202 in patients with relapsed or refractory hematologic malignancies.

The second (UTX-TGR-103, NCT02006485) is a phase 1/1b trial evaluating the combination of ublituximab and TGR-1202 in patients with relapsed or refractory non-Hodgkin lymphoma or CLL.

At ASH 2015, researchers reported results of a phase 1 trial (TGR-GA-106, NCT02100852) of TGR-1202 in combination with obinutuzumab and chlorambucil in patients with CLL.

Dendritic cells in skin

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for SL-401 in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies.

SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

The drug is under development by Stemline Therapeutics, Inc.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 2 trial of SL-401

The breakthrough designation for SL-401 was supported by data from a phase 2 trial of patients with BPDCN or acute myeloid leukemia. Results observed in the BPDCN patients were presented at the 2016 EHA Congress (abstract S812).

The study consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

At the data cut-off, 18 BPDCN patients had received SL-401 at 7 μg/kg (n=3, stage 1) or 12 μg/kg (n=15, 6 in stage 1, 9 in stage 2).

Fifteen of these patients were evaluable for response. The overall response rate was 87% (13/15). All 10 previously untreated BPDCN patients achieved a response, including 7 complete responses (CRs).

All 8 previously untreated BPDCN patients treated at the optimal dose (12 μg/kg) achieved a response, including 6 CRs. Four of these patients were still on SL-401 and in CR at the data cutoff, and 2 had gone on to stem cell transplant.

The most common treatment-related adverse events in the BPDCN patients were transient transaminase elevation (57%), hypoalbuminemia (40%), and transient thrombocytopenia (15%).

In stage 1, two patients had capillary leak syndrome (CLS)—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS. There have been no cases of severe CLS since then.

Dendritic cells in skin

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for SL-401 in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies.

SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

The drug is under development by Stemline Therapeutics, Inc.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 2 trial of SL-401

The breakthrough designation for SL-401 was supported by data from a phase 2 trial of patients with BPDCN or acute myeloid leukemia. Results observed in the BPDCN patients were presented at the 2016 EHA Congress (abstract S812).

The study consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

At the data cut-off, 18 BPDCN patients had received SL-401 at 7 μg/kg (n=3, stage 1) or 12 μg/kg (n=15, 6 in stage 1, 9 in stage 2).

Fifteen of these patients were evaluable for response. The overall response rate was 87% (13/15). All 10 previously untreated BPDCN patients achieved a response, including 7 complete responses (CRs).

All 8 previously untreated BPDCN patients treated at the optimal dose (12 μg/kg) achieved a response, including 6 CRs. Four of these patients were still on SL-401 and in CR at the data cutoff, and 2 had gone on to stem cell transplant.

The most common treatment-related adverse events in the BPDCN patients were transient transaminase elevation (57%), hypoalbuminemia (40%), and transient thrombocytopenia (15%).

In stage 1, two patients had capillary leak syndrome (CLS)—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS. There have been no cases of severe CLS since then.

Dendritic cells in skin

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for SL-401 in the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN).

SL-401 is a targeted therapy directed to the interleukin-3 receptor (IL-3R), which is present in BPDCN and other hematologic malignancies.

SL-401 is composed of human IL-3 coupled to a truncated diphtheria toxin payload that inhibits protein synthesis.

The drug is under development by Stemline Therapeutics, Inc.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Phase 2 trial of SL-401

The breakthrough designation for SL-401 was supported by data from a phase 2 trial of patients with BPDCN or acute myeloid leukemia. Results observed in the BPDCN patients were presented at the 2016 EHA Congress (abstract S812).

The study consists of a lead-in dose-escalation stage (stage 1) and subsequent expansion stage (stage 2). In stage 1, patients received SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg/day) every 21 days. In stage 2, patients received SL-401 at the optimal stage 1 dose—12 μg/kg.

At the data cut-off, 18 BPDCN patients had received SL-401 at 7 μg/kg (n=3, stage 1) or 12 μg/kg (n=15, 6 in stage 1, 9 in stage 2).

Fifteen of these patients were evaluable for response. The overall response rate was 87% (13/15). All 10 previously untreated BPDCN patients achieved a response, including 7 complete responses (CRs).

All 8 previously untreated BPDCN patients treated at the optimal dose (12 μg/kg) achieved a response, including 6 CRs. Four of these patients were still on SL-401 and in CR at the data cutoff, and 2 had gone on to stem cell transplant.

The most common treatment-related adverse events in the BPDCN patients were transient transaminase elevation (57%), hypoalbuminemia (40%), and transient thrombocytopenia (15%).

In stage 1, two patients had capillary leak syndrome (CLS)—one grade 5 (7 μg/kg) and one grade 4 (12 μg/kg). After this, safety precautions were implemented to minimize the risk of severe CLS. There have been no cases of severe CLS since then.

Macrophage in a mouse

Image from Flickr

The US Food and Drug Administration (FDA) has granted orphan drug designation for dusquetide as a treatment for macrophage activation syndrome (MAS).

Dusquetide is an innate defense regulator, a new class of short, synthetic peptides that accelerate bacterial clearance and resolution of tissue damage while modulating inflammation following exposure to bacterial pathogens, radiation, chemotherapy, and other agents.

According to researchers, dusquetide has demonstrated preclinical efficacy and safety in several animal models.

In a mouse model of MAS, dusquetide was shown to reduce pancytopenia, inhibit IL-12 responses, and improve body weight maintenance.

SGX942, the drug product containing dusquetide, has demonstrated safety in a phase 1 study of 84 healthy volunteers.

In addition, SGX942 has demonstrated preliminary efficacy and safety in an exploratory phase 2 study of 111 patients with oral mucositis due to chemoradiation therapy for head and neck cancer.

SGX942 is being developed by Solgenix, Inc.

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the drug is approved.

About MAS

MAS is a life-threatening complication of rheumatic disease that, for unknown reasons, frequently occurs in individuals with systemic juvenile idiopathic arthritis. MAS also occurs in patients with systemic lupus erythematosus, Kawasaki disease, adult-onset Still’s disease, and various vasculitic syndromes.

MAS is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms.

MAS is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. 

Macrophage in a mouse

Image from Flickr

The US Food and Drug Administration (FDA) has granted orphan drug designation for dusquetide as a treatment for macrophage activation syndrome (MAS).

Dusquetide is an innate defense regulator, a new class of short, synthetic peptides that accelerate bacterial clearance and resolution of tissue damage while modulating inflammation following exposure to bacterial pathogens, radiation, chemotherapy, and other agents.

According to researchers, dusquetide has demonstrated preclinical efficacy and safety in several animal models.

In a mouse model of MAS, dusquetide was shown to reduce pancytopenia, inhibit IL-12 responses, and improve body weight maintenance.

SGX942, the drug product containing dusquetide, has demonstrated safety in a phase 1 study of 84 healthy volunteers.

In addition, SGX942 has demonstrated preliminary efficacy and safety in an exploratory phase 2 study of 111 patients with oral mucositis due to chemoradiation therapy for head and neck cancer.

SGX942 is being developed by Solgenix, Inc.

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the drug is approved.

About MAS

MAS is a life-threatening complication of rheumatic disease that, for unknown reasons, frequently occurs in individuals with systemic juvenile idiopathic arthritis. MAS also occurs in patients with systemic lupus erythematosus, Kawasaki disease, adult-onset Still’s disease, and various vasculitic syndromes.

MAS is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms.

MAS is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. 

Macrophage in a mouse

Image from Flickr

The US Food and Drug Administration (FDA) has granted orphan drug designation for dusquetide as a treatment for macrophage activation syndrome (MAS).

Dusquetide is an innate defense regulator, a new class of short, synthetic peptides that accelerate bacterial clearance and resolution of tissue damage while modulating inflammation following exposure to bacterial pathogens, radiation, chemotherapy, and other agents.

According to researchers, dusquetide has demonstrated preclinical efficacy and safety in several animal models.

In a mouse model of MAS, dusquetide was shown to reduce pancytopenia, inhibit IL-12 responses, and improve body weight maintenance.

SGX942, the drug product containing dusquetide, has demonstrated safety in a phase 1 study of 84 healthy volunteers.

In addition, SGX942 has demonstrated preliminary efficacy and safety in an exploratory phase 2 study of 111 patients with oral mucositis due to chemoradiation therapy for head and neck cancer.

SGX942 is being developed by Solgenix, Inc.

About orphan designation

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the drug is approved.

About MAS

MAS is a life-threatening complication of rheumatic disease that, for unknown reasons, frequently occurs in individuals with systemic juvenile idiopathic arthritis. MAS also occurs in patients with systemic lupus erythematosus, Kawasaki disease, adult-onset Still’s disease, and various vasculitic syndromes.

MAS is characterized by pancytopenia, liver insufficiency, coagulopathy, and neurologic symptoms.

MAS is thought to be caused by the activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages, leading to widespread hemophagocytosis and cytokine overproduction. 

Apixaban (Eliquis)

Photo courtesy of Pfizer

and Bristol-Myers Squibb

The US Food and Drug Administration (FDA) has issued a complete response letter regarding the biologics license application for andexanet alfa (AndexXa™).

Andexanet alfa is being developed as a reversal agent for the factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and enoxaparin.

The agent is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

In the complete response letter, the FDA requested that Portola Pharmaceuticals Inc., the company developing andexanet alfa, provide additional information related to manufacturing.

Portola said it could not provide many details on this request but stressed that the FDA did not question the company’s ability to manufacture the drug.

The FDA also asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.

The completed phase 3 studies of andexanet alfa were designed to assess the drug’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers. Andexanet alfa’s effects on edoxaban and enoxaparin have been investigated in phase 2 studies, however.

Portola had assumed these studies would be sufficient because, overall, the research suggests andexanet alfa has broad activity against factor Xa inhibitors, according to Bill Lis, chief executive officer of Portola.

Lis also noted that the primary use of andexanet alfa, once approved, would be in patients receiving rivaroxaban or apixaban because fewer patients take edoxaban and enoxaparin.

The final issue the FDA mentioned in the complete response letter was the need to finalize its review of the clinical amendments to Portola’s post-marketing commitments.

“Because AndexXa addresses an urgent unmet medical need, we and the FDA are committed to resolving the outstanding questions and determining appropriate next steps,” Lis said.

“Portola’s goal is to define the most expedient path to approval so we can meet the needs of these patients who have no alternative. We plan to meet with the FDA as soon as possible.”

About andexanet alfa

Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.

The FDA granted andexanet alfa orphan drug designation last year and breakthrough therapy designation in 2013.

Portola’s biologics license application for andexanet alfa was based on data from a pair of phase 3 studies of healthy volunteers—ANNEXA-A and ANNEXA-R.

In the ANNEXA-R trial, andexanet alfa successfully reversed the anticoagulant activity of rivaroxaban. In the ANNEXA-A trial, andexanet alfa reversed the anticoagulant activity of apixaban.

Results from these studies were published in NEJM last year.

The biologics license application also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study.

In this phase 3b/4 study, researchers are evaluating andexanet alfa in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed.

Apixaban (Eliquis)

Photo courtesy of Pfizer

and Bristol-Myers Squibb

The US Food and Drug Administration (FDA) has issued a complete response letter regarding the biologics license application for andexanet alfa (AndexXa™).

Andexanet alfa is being developed as a reversal agent for the factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and enoxaparin.

The agent is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

In the complete response letter, the FDA requested that Portola Pharmaceuticals Inc., the company developing andexanet alfa, provide additional information related to manufacturing.

Portola said it could not provide many details on this request but stressed that the FDA did not question the company’s ability to manufacture the drug.

The FDA also asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.

The completed phase 3 studies of andexanet alfa were designed to assess the drug’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers. Andexanet alfa’s effects on edoxaban and enoxaparin have been investigated in phase 2 studies, however.

Portola had assumed these studies would be sufficient because, overall, the research suggests andexanet alfa has broad activity against factor Xa inhibitors, according to Bill Lis, chief executive officer of Portola.

Lis also noted that the primary use of andexanet alfa, once approved, would be in patients receiving rivaroxaban or apixaban because fewer patients take edoxaban and enoxaparin.

The final issue the FDA mentioned in the complete response letter was the need to finalize its review of the clinical amendments to Portola’s post-marketing commitments.

“Because AndexXa addresses an urgent unmet medical need, we and the FDA are committed to resolving the outstanding questions and determining appropriate next steps,” Lis said.

“Portola’s goal is to define the most expedient path to approval so we can meet the needs of these patients who have no alternative. We plan to meet with the FDA as soon as possible.”

About andexanet alfa

Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.

The FDA granted andexanet alfa orphan drug designation last year and breakthrough therapy designation in 2013.

Portola’s biologics license application for andexanet alfa was based on data from a pair of phase 3 studies of healthy volunteers—ANNEXA-A and ANNEXA-R.

In the ANNEXA-R trial, andexanet alfa successfully reversed the anticoagulant activity of rivaroxaban. In the ANNEXA-A trial, andexanet alfa reversed the anticoagulant activity of apixaban.

Results from these studies were published in NEJM last year.

The biologics license application also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study.

In this phase 3b/4 study, researchers are evaluating andexanet alfa in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed.

Apixaban (Eliquis)

Photo courtesy of Pfizer

and Bristol-Myers Squibb

The US Food and Drug Administration (FDA) has issued a complete response letter regarding the biologics license application for andexanet alfa (AndexXa™).

Andexanet alfa is being developed as a reversal agent for the factor Xa inhibitors apixaban, rivaroxaban, edoxaban, and enoxaparin.

The agent is intended to be used when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

In the complete response letter, the FDA requested that Portola Pharmaceuticals Inc., the company developing andexanet alfa, provide additional information related to manufacturing.

Portola said it could not provide many details on this request but stressed that the FDA did not question the company’s ability to manufacture the drug.

The FDA also asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label.

The completed phase 3 studies of andexanet alfa were designed to assess the drug’s ability to reverse the effects of apixaban and rivaroxaban—but not edoxaban or enoxaparin—in healthy volunteers. Andexanet alfa’s effects on edoxaban and enoxaparin have been investigated in phase 2 studies, however.

Portola had assumed these studies would be sufficient because, overall, the research suggests andexanet alfa has broad activity against factor Xa inhibitors, according to Bill Lis, chief executive officer of Portola.

Lis also noted that the primary use of andexanet alfa, once approved, would be in patients receiving rivaroxaban or apixaban because fewer patients take edoxaban and enoxaparin.

The final issue the FDA mentioned in the complete response letter was the need to finalize its review of the clinical amendments to Portola’s post-marketing commitments.

“Because AndexXa addresses an urgent unmet medical need, we and the FDA are committed to resolving the outstanding questions and determining appropriate next steps,” Lis said.

“Portola’s goal is to define the most expedient path to approval so we can meet the needs of these patients who have no alternative. We plan to meet with the FDA as soon as possible.”

About andexanet alfa

Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.

The FDA granted andexanet alfa orphan drug designation last year and breakthrough therapy designation in 2013.

Portola’s biologics license application for andexanet alfa was based on data from a pair of phase 3 studies of healthy volunteers—ANNEXA-A and ANNEXA-R.

In the ANNEXA-R trial, andexanet alfa successfully reversed the anticoagulant activity of rivaroxaban. In the ANNEXA-A trial, andexanet alfa reversed the anticoagulant activity of apixaban.

Results from these studies were published in NEJM last year.

The biologics license application also included limited adjudicated efficacy and safety data from initial patients enrolled in the ongoing ANNEXA-4 study.

In this phase 3b/4 study, researchers are evaluating andexanet alfa in patients receiving apixaban, rivaroxaban, edoxaban, or enoxaparin who present with an acute major bleed.