FDA grants drug accelerated approval for CLL

Prescription medications

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has granted accelerated approval for venetoclax (Venclexta) to treat patients with chronic lymphocytic leukemia (CLL) who have 17p deletion and have received at least one prior therapy.

Venetoclax will be available in the US within about a week, according to the companies developing the drug, AbbVie and Genentech (a member of the

Roche Group).

The companies said they plan to offer patient assistance programs for qualifying patients who wish to receive venetoclax.

Venetoclax (formerly ABT-199) is the first FDA-approved treatment that targets the BCL-2 protein, which is overexpressed in many patients with CLL.

The drug is indicated for daily use after 17p deletion is confirmed via the FDA-approved companion diagnostic Vysis CLL FISH probe kit, which is manufactured by Abbott Molecular.

The FDA granted venetoclax accelerated approval rather than traditional approval because the drug has not yet shown a clinical benefit. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of venetoclax for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted venetoclax breakthrough therapy designation, priority review status, and orphan drug designation.

Phase 2 trial

Results from the pivotal phase 2 trial of venetoclax (M13-982, NCT01889186) were presented at the 2015 ASH Annual Meeting. According to those data, the trial enrolled 107 patients with relapsed or refractory CLL and 17p deletion.

Patients received venetoclax at 400 mg once daily following a weekly ramp-up schedule for the first 5 weeks. The primary endpoint was overall response rate, as determined by an independent review committee.

Eighty-five patients responded to treatment, for an overall response rate of 79.4%. Eight patients (7.5%) achieved a complete response or complete response with incomplete count recovery, 3 (2.8%) had a near partial response, and 74 (69.2%) had a partial response. Twenty-two patients (20.6%) did not respond.

As of the ASH presentation, the median duration of response had not been reached. The same was true for progression-free survival and overall survival. The progression-free survival estimate for 12 months was 72.0%, and the overall survival estimate was 86.7%.

Treatment-emergent adverse events of any grade occurred in 96% of patients. The most frequent were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%), fatigue (22%), pyrexia (20%), thrombocytopenia (19%), hyperphosphatemia (16%), vomiting (15%), and upper respiratory tract infection (15%). (About 22% of patients had neutropenia at baseline.)

The most frequent grade 3/4 adverse events were neutropenia (40%), anemia (18%), and thrombocytopenia (15%). Infections occurred in 72% of patients, with 20% of patients experiencing grade 3 or higher infections.

Serious adverse events occurred in 55% of patients, the most common being pyrexia (7%), autoimmune hemolytic anemia (7%), pneumonia (6%), and febrile neutropenia (5%).

Laboratory tumor lysis syndrome (TLS) occurred in 5 patients during the ramp-up period only. Two patients required a dose interruption of 1 day each. There were no clinical TLS events.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

Venetoclax is currently being evaluated in phase 3 trials for the treatment of relapsed, refractory, and previously untreated CLL.

Prescription medications

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has granted accelerated approval for venetoclax (Venclexta) to treat patients with chronic lymphocytic leukemia (CLL) who have 17p deletion and have received at least one prior therapy.

Venetoclax will be available in the US within about a week, according to the companies developing the drug, AbbVie and Genentech (a member of the

Roche Group).

The companies said they plan to offer patient assistance programs for qualifying patients who wish to receive venetoclax.

Venetoclax (formerly ABT-199) is the first FDA-approved treatment that targets the BCL-2 protein, which is overexpressed in many patients with CLL.

The drug is indicated for daily use after 17p deletion is confirmed via the FDA-approved companion diagnostic Vysis CLL FISH probe kit, which is manufactured by Abbott Molecular.

The FDA granted venetoclax accelerated approval rather than traditional approval because the drug has not yet shown a clinical benefit. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of venetoclax for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted venetoclax breakthrough therapy designation, priority review status, and orphan drug designation.

Phase 2 trial

Results from the pivotal phase 2 trial of venetoclax (M13-982, NCT01889186) were presented at the 2015 ASH Annual Meeting. According to those data, the trial enrolled 107 patients with relapsed or refractory CLL and 17p deletion.

Patients received venetoclax at 400 mg once daily following a weekly ramp-up schedule for the first 5 weeks. The primary endpoint was overall response rate, as determined by an independent review committee.

Eighty-five patients responded to treatment, for an overall response rate of 79.4%. Eight patients (7.5%) achieved a complete response or complete response with incomplete count recovery, 3 (2.8%) had a near partial response, and 74 (69.2%) had a partial response. Twenty-two patients (20.6%) did not respond.

As of the ASH presentation, the median duration of response had not been reached. The same was true for progression-free survival and overall survival. The progression-free survival estimate for 12 months was 72.0%, and the overall survival estimate was 86.7%.

Treatment-emergent adverse events of any grade occurred in 96% of patients. The most frequent were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%), fatigue (22%), pyrexia (20%), thrombocytopenia (19%), hyperphosphatemia (16%), vomiting (15%), and upper respiratory tract infection (15%). (About 22% of patients had neutropenia at baseline.)

The most frequent grade 3/4 adverse events were neutropenia (40%), anemia (18%), and thrombocytopenia (15%). Infections occurred in 72% of patients, with 20% of patients experiencing grade 3 or higher infections.

Serious adverse events occurred in 55% of patients, the most common being pyrexia (7%), autoimmune hemolytic anemia (7%), pneumonia (6%), and febrile neutropenia (5%).

Laboratory tumor lysis syndrome (TLS) occurred in 5 patients during the ramp-up period only. Two patients required a dose interruption of 1 day each. There were no clinical TLS events.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

Venetoclax is currently being evaluated in phase 3 trials for the treatment of relapsed, refractory, and previously untreated CLL.

Prescription medications

Photo courtesy of the CDC

The US Food and Drug Administration (FDA) has granted accelerated approval for venetoclax (Venclexta) to treat patients with chronic lymphocytic leukemia (CLL) who have 17p deletion and have received at least one prior therapy.

Venetoclax will be available in the US within about a week, according to the companies developing the drug, AbbVie and Genentech (a member of the

Roche Group).

The companies said they plan to offer patient assistance programs for qualifying patients who wish to receive venetoclax.

Venetoclax (formerly ABT-199) is the first FDA-approved treatment that targets the BCL-2 protein, which is overexpressed in many patients with CLL.

The drug is indicated for daily use after 17p deletion is confirmed via the FDA-approved companion diagnostic Vysis CLL FISH probe kit, which is manufactured by Abbott Molecular.

The FDA granted venetoclax accelerated approval rather than traditional approval because the drug has not yet shown a clinical benefit. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of venetoclax for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted venetoclax breakthrough therapy designation, priority review status, and orphan drug designation.

Phase 2 trial

Results from the pivotal phase 2 trial of venetoclax (M13-982, NCT01889186) were presented at the 2015 ASH Annual Meeting. According to those data, the trial enrolled 107 patients with relapsed or refractory CLL and 17p deletion.

Patients received venetoclax at 400 mg once daily following a weekly ramp-up schedule for the first 5 weeks. The primary endpoint was overall response rate, as determined by an independent review committee.

Eighty-five patients responded to treatment, for an overall response rate of 79.4%. Eight patients (7.5%) achieved a complete response or complete response with incomplete count recovery, 3 (2.8%) had a near partial response, and 74 (69.2%) had a partial response. Twenty-two patients (20.6%) did not respond.

As of the ASH presentation, the median duration of response had not been reached. The same was true for progression-free survival and overall survival. The progression-free survival estimate for 12 months was 72.0%, and the overall survival estimate was 86.7%.

Treatment-emergent adverse events of any grade occurred in 96% of patients. The most frequent were neutropenia (43%), diarrhea (29%), nausea (29%), anemia (27%), fatigue (22%), pyrexia (20%), thrombocytopenia (19%), hyperphosphatemia (16%), vomiting (15%), and upper respiratory tract infection (15%). (About 22% of patients had neutropenia at baseline.)

The most frequent grade 3/4 adverse events were neutropenia (40%), anemia (18%), and thrombocytopenia (15%). Infections occurred in 72% of patients, with 20% of patients experiencing grade 3 or higher infections.

Serious adverse events occurred in 55% of patients, the most common being pyrexia (7%), autoimmune hemolytic anemia (7%), pneumonia (6%), and febrile neutropenia (5%).

Laboratory tumor lysis syndrome (TLS) occurred in 5 patients during the ramp-up period only. Two patients required a dose interruption of 1 day each. There were no clinical TLS events.

In the past, TLS has caused deaths in patients receiving venetoclax. In response, AbbVie stopped dose-escalation in patients receiving the drug and suspended enrollment in phase 1 trials.

However, researchers subsequently found that a modified dosing schedule, prophylaxis, and patient monitoring can reduce the risk of TLS.

Venetoclax is currently being evaluated in phase 3 trials for the treatment of relapsed, refractory, and previously untreated CLL.