Drug produces mixed results in myelofibrosis

Micrograph showing MF

Two phase 3 trials have shown mixed results in myelofibrosis (MF) patients receiving the JAK inhibitor momelotinib, according to Gilead Sciences, Inc., the company developing the drug.

In the SIMPLIFY-1 study, momelotinib proved non-inferior to ruxolitinib when it came to the study’s primary endpoint but not its key secondary

endpoint.

In the SIMPLIFY-2 trial, momelotinib was not superior to best available therapy (BAT) with regard to the primary endpoint.

However, there were differences in favor of momelotinib when it came to some secondary endpoints.

“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” said Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, Inc.

“We plan to discuss these results with regulatory authorities to determine the next steps.”

About the studies

The SIMPLIFY studies are randomized, phase 3 trials designed to evaluate momelotinib in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. The trials have the same primary and secondary endpoints.

The primary efficacy endpoint is splenic response rate at week 24 (SRR24), defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume at week 24, as measured by MRI or CT scan.

Secondary endpoints include:

• Response rate in total symptom score (TSS) at week 24, defined as the proportion of patients achieving ≥ 50% reduction in symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score diary
• The proportion of patients who are transfusion-independent at week 24, defined as no red blood cell transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks
• The proportion who are transfusion-dependent at week 24, defined as at least 4 units of red blood cell transfusion or hemoglobin level below 8 g/dL in the prior 8 weeks
• The rate of red blood cell transfusion through week 24.

SIMPLIFY-1 trial

In SIMPLIFY-1, a double-blind, active-controlled study, 432 MF patients who had not previously been treated with a JAK inhibitor were randomized (1:1) to receive momelotinib or ruxolitinib for 24 weeks.

The study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for SRR24. The incidence of SRR24 was 26.5% in the momelotinib arm and 29.0% in the ruxolitinib arm (95% CI: -11.2% to +5.6%; P=0.011).

However, non-inferiority was not achieved for the key secondary endpoint of response rate in TSS.

Greater improvements in all 3 anemia-related secondary endpoints—transfusion independence, transfusion dependence, and transfusion rate—were observed in patients receiving momelotinib compared to ruxolitinib.

However, because the TSS response rate did not meet the non-inferiority test, formal sequential statistical testing was not undertaken for these 3 secondary endpoints.

During 24 weeks of treatment in SIMPLIFY-1, the most frequent adverse events in patients receiving momelotinib were thrombocytopenia, diarrhea, headache, dizziness, and nausea.

The most frequent adverse events in patients receiving ruxolitinib were anemia, thrombocytopenia, diarrhea, headache, and dizziness.

Ten percent of patients receiving momelotinib reported peripheral neuropathy (any grade), compared to 5% of ruxolitinib-treated patients. There was no grade 3 or higher peripheral neuropathy in momelotinib-treated patients, but there was 1 case in the ruxolitinib arm.

SIMPLIFY-2 trial

In SIMPLIFY-2, 156 patients previously treated with, but not refractory to, ruxolitinib were randomized (2:1) to receive momelotinib or BAT for 24 weeks.

Eighty-eight percent of patients randomized to the BAT arm continued to receive ruxolitinib. The remainder of patients received chemotherapy, interferon, corticosteroids, other therapies, or some combination thereof.

The study’s primary endpoint was not met. Momelotinib did not prove superior to BAT with regard to SRR24. The incidence of SRR24 was 6.7% in the momelotinib arm and 5.8% in the BAT arm (95% CI: -8.9% to +10.2%; P=0.90).

Differences in favor of momelotinib were observed for the secondary endpoints of TSS and transfusion independence. However, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.

Gilead did not release safety data from this trial. The company said detailed results from both SIMPLIFY studies will be submitted for presentation at upcoming scientific conferences.

Micrograph showing MF

Two phase 3 trials have shown mixed results in myelofibrosis (MF) patients receiving the JAK inhibitor momelotinib, according to Gilead Sciences, Inc., the company developing the drug.

In the SIMPLIFY-1 study, momelotinib proved non-inferior to ruxolitinib when it came to the study’s primary endpoint but not its key secondary

endpoint.

In the SIMPLIFY-2 trial, momelotinib was not superior to best available therapy (BAT) with regard to the primary endpoint.

However, there were differences in favor of momelotinib when it came to some secondary endpoints.

“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” said Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, Inc.

“We plan to discuss these results with regulatory authorities to determine the next steps.”

About the studies

The SIMPLIFY studies are randomized, phase 3 trials designed to evaluate momelotinib in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. The trials have the same primary and secondary endpoints.

The primary efficacy endpoint is splenic response rate at week 24 (SRR24), defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume at week 24, as measured by MRI or CT scan.

Secondary endpoints include:

• Response rate in total symptom score (TSS) at week 24, defined as the proportion of patients achieving ≥ 50% reduction in symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score diary
• The proportion of patients who are transfusion-independent at week 24, defined as no red blood cell transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks
• The proportion who are transfusion-dependent at week 24, defined as at least 4 units of red blood cell transfusion or hemoglobin level below 8 g/dL in the prior 8 weeks
• The rate of red blood cell transfusion through week 24.

SIMPLIFY-1 trial

In SIMPLIFY-1, a double-blind, active-controlled study, 432 MF patients who had not previously been treated with a JAK inhibitor were randomized (1:1) to receive momelotinib or ruxolitinib for 24 weeks.

The study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for SRR24. The incidence of SRR24 was 26.5% in the momelotinib arm and 29.0% in the ruxolitinib arm (95% CI: -11.2% to +5.6%; P=0.011).

However, non-inferiority was not achieved for the key secondary endpoint of response rate in TSS.

Greater improvements in all 3 anemia-related secondary endpoints—transfusion independence, transfusion dependence, and transfusion rate—were observed in patients receiving momelotinib compared to ruxolitinib.

However, because the TSS response rate did not meet the non-inferiority test, formal sequential statistical testing was not undertaken for these 3 secondary endpoints.

During 24 weeks of treatment in SIMPLIFY-1, the most frequent adverse events in patients receiving momelotinib were thrombocytopenia, diarrhea, headache, dizziness, and nausea.

The most frequent adverse events in patients receiving ruxolitinib were anemia, thrombocytopenia, diarrhea, headache, and dizziness.

Ten percent of patients receiving momelotinib reported peripheral neuropathy (any grade), compared to 5% of ruxolitinib-treated patients. There was no grade 3 or higher peripheral neuropathy in momelotinib-treated patients, but there was 1 case in the ruxolitinib arm.

SIMPLIFY-2 trial

In SIMPLIFY-2, 156 patients previously treated with, but not refractory to, ruxolitinib were randomized (2:1) to receive momelotinib or BAT for 24 weeks.

Eighty-eight percent of patients randomized to the BAT arm continued to receive ruxolitinib. The remainder of patients received chemotherapy, interferon, corticosteroids, other therapies, or some combination thereof.

The study’s primary endpoint was not met. Momelotinib did not prove superior to BAT with regard to SRR24. The incidence of SRR24 was 6.7% in the momelotinib arm and 5.8% in the BAT arm (95% CI: -8.9% to +10.2%; P=0.90).

Differences in favor of momelotinib were observed for the secondary endpoints of TSS and transfusion independence. However, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.

Gilead did not release safety data from this trial. The company said detailed results from both SIMPLIFY studies will be submitted for presentation at upcoming scientific conferences.

Micrograph showing MF

Two phase 3 trials have shown mixed results in myelofibrosis (MF) patients receiving the JAK inhibitor momelotinib, according to Gilead Sciences, Inc., the company developing the drug.

In the SIMPLIFY-1 study, momelotinib proved non-inferior to ruxolitinib when it came to the study’s primary endpoint but not its key secondary

endpoint.

In the SIMPLIFY-2 trial, momelotinib was not superior to best available therapy (BAT) with regard to the primary endpoint.

However, there were differences in favor of momelotinib when it came to some secondary endpoints.

“The results from both the SIMPLIFY-1 and SIMPLIFY-2 studies indicate that momelotinib provides some treatment benefit, including benefit on anemia-related endpoints,” said Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, Inc.

“We plan to discuss these results with regulatory authorities to determine the next steps.”

About the studies

The SIMPLIFY studies are randomized, phase 3 trials designed to evaluate momelotinib in patients with primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF. The trials have the same primary and secondary endpoints.

The primary efficacy endpoint is splenic response rate at week 24 (SRR24), defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume at week 24, as measured by MRI or CT scan.

Secondary endpoints include:

• Response rate in total symptom score (TSS) at week 24, defined as the proportion of patients achieving ≥ 50% reduction in symptoms, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score diary
• The proportion of patients who are transfusion-independent at week 24, defined as no red blood cell transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks
• The proportion who are transfusion-dependent at week 24, defined as at least 4 units of red blood cell transfusion or hemoglobin level below 8 g/dL in the prior 8 weeks
• The rate of red blood cell transfusion through week 24.

SIMPLIFY-1 trial

In SIMPLIFY-1, a double-blind, active-controlled study, 432 MF patients who had not previously been treated with a JAK inhibitor were randomized (1:1) to receive momelotinib or ruxolitinib for 24 weeks.

The study achieved its pre-specified primary endpoint of non-inferiority to ruxolitinib for SRR24. The incidence of SRR24 was 26.5% in the momelotinib arm and 29.0% in the ruxolitinib arm (95% CI: -11.2% to +5.6%; P=0.011).

However, non-inferiority was not achieved for the key secondary endpoint of response rate in TSS.

Greater improvements in all 3 anemia-related secondary endpoints—transfusion independence, transfusion dependence, and transfusion rate—were observed in patients receiving momelotinib compared to ruxolitinib.

However, because the TSS response rate did not meet the non-inferiority test, formal sequential statistical testing was not undertaken for these 3 secondary endpoints.

During 24 weeks of treatment in SIMPLIFY-1, the most frequent adverse events in patients receiving momelotinib were thrombocytopenia, diarrhea, headache, dizziness, and nausea.

The most frequent adverse events in patients receiving ruxolitinib were anemia, thrombocytopenia, diarrhea, headache, and dizziness.

Ten percent of patients receiving momelotinib reported peripheral neuropathy (any grade), compared to 5% of ruxolitinib-treated patients. There was no grade 3 or higher peripheral neuropathy in momelotinib-treated patients, but there was 1 case in the ruxolitinib arm.

SIMPLIFY-2 trial

In SIMPLIFY-2, 156 patients previously treated with, but not refractory to, ruxolitinib were randomized (2:1) to receive momelotinib or BAT for 24 weeks.

Eighty-eight percent of patients randomized to the BAT arm continued to receive ruxolitinib. The remainder of patients received chemotherapy, interferon, corticosteroids, other therapies, or some combination thereof.

The study’s primary endpoint was not met. Momelotinib did not prove superior to BAT with regard to SRR24. The incidence of SRR24 was 6.7% in the momelotinib arm and 5.8% in the BAT arm (95% CI: -8.9% to +10.2%; P=0.90).

Differences in favor of momelotinib were observed for the secondary endpoints of TSS and transfusion independence. However, formal sequential statistical testing was not undertaken because the primary superiority endpoint was not achieved.

Gilead did not release safety data from this trial. The company said detailed results from both SIMPLIFY studies will be submitted for presentation at upcoming scientific conferences.