Sierra Oncology Reports Positive Results in Pivotal Trial of Momelotinib for Myelofibrosis

Rare cancer drug developer Sierra Oncology reported positive topline data from the pivotal phase 3 MOMENTUM study evaluating momelotinib in myelofibrosis patients who are symptomatic and anemic and previously treated with an approved JAK inhibitor.

Photo: Stephen Dilly, president and CEO of Sierra Oncology

The trial met all its primary and key secondary endpoints, the first and only JAK inhibitor to demonstrate positive data for all key hallmarks of the disease—symptoms, splenic response and anemia.

The results are stunning considering that Gilead Sciences had failed to advance the program after buying momelotinib from YM Biosciences in 2012 for $510 million and selling it to Sierra Oncology for $3 million in 2018.

“These data are extremely exciting and everything we had hoped to see from the trial,” said Stephen Dilly, president and CEO of Sierra Oncology. “To achieve statistically significant and clinically important efficacy across all prespecified primary and key secondary endpoints while maintaining platelet counts in such a difficult to treat patient population is remarkable, and a confirmation of the anemia response we identified in the comprehensive review of our previous phase 3 studies.”

Myelofibrosis is a rare blood cancer that results from dysregulated JAK-STAT signaling and is characterized by constitutional symptoms, splenomegaly (enlarged spleen) and progressive anemia. From prior studies with momelotinib, Sierra has found that approximately half of myelofibrosis patients are moderately to severely anemic when eligible for JAK inhibitor treatment. Furthermore, currently approved JAK inhibitors only address symptoms and splenomegaly and are myelosuppressive. This can lead to worsening anemia, resulting in dose reductions that potentially reduce treatment effect.

Momelotinib is a potent, selective and orally bioavailable JAK1, JAK2 and ACVR1 / ALK2 inhibitor under investigation for the treatment of myelofibrosis in symptomatic, anemic patients previously treated with an approved JAK inhibitor. More than 1,200 subjects have received momelotinib since clinical studies began in 2009, including approximately 1,000 patients treated for myelofibrosis, several of whom have remained on treatment for more than 11 years.

MOMENTUM is a global, randomized, double-blind phase 3 clinical trial of momelotinib versus danazol in patients with myelofibrosis who were symptomatic and anemic, and had been previously treated with an FDA-approved JAK inhibitor. The study was designed to evaluate the safety and efficacy of momelotinib for the treatment and reduction of the key hallmarks of disease: symptoms, blood transfusions (due to anemia) and splenomegaly (enlarged spleen).

The primary endpoint of the study is Total Symptom Score (TSS) reduction of >50% over the 28 days immediately prior to the end of Week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form (MFSAF). Secondary endpoints included Transfusion Independence (TI) rate for >12 weeks immediately prior to the end of Week 24 with Hgb levels ≥ 8 g/dL, and Splenic Response Rate (SRR) based on splenic volume reduction of >35% at Week 24. The study enrolled 195 patients based on a planned 180 patients across 21 countries.

Danazol was selected as the treatment comparator given its use to ameliorate anemia in patients with myelofibrosis, as recommended by National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines. Patients were randomized 2:1 to receive either momelotinib or danazol. After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early cross-over to momelotinib was available for confirmed symptomatic splenic progression.

The primary endpoint of Total Symptom Score of >50 percent was achieved by 25 percent in the MMB arm vs. 9 percent in the control arm. The secondary endpoint of Transfusion Independence was achieved by 31 percent in the MMB arm vs. 20 percent in the control arm, showing non-inferiority. The secondary endpoint of Splenic Response Rate >35 percent was achieved by 23 percent in the MMB arm vs. 3 percent in the control arm.

The rate of Grade 3 or worse adverse events in the randomized treatment period was 54 percent in the MMB arm and 65 percent in the control arm. Serious treatment emergent adverse events were 35 percent in the MMB arm and 40 percent in the control arm.

Mean baseline characteristics for all patients were Total Symptom Score of 27, Hemoglobin of 8 g/dL and platelet count of 145 x 10 9/L.

Sierra Oncology will present the full data set at an upcoming medical meeting.

“Anemia of myelofibrosis is strongly correlated with reduced quality of life and a decrease in overall survival. Half of all myelofibrosis patients present with anemia at diagnosis and virtually all become anemic over time,” said Ruben Mesa, executive director of the Mays Cancer Center, home to UT Health San Antonio, MD Anderson Cancer Center, and co-principal investigator of the study. “With currently approved therapies being myelosuppressive, it’s wonderful to know that we may soon have such an effective treatment option for these patients.”

Author: Rare Daily Staff