A drug abandoned by Gilead Sciences has far better prospects under Sierra Oncology. A growing body of pivotal clinical data supports small-molecule cases as a better treatment option for rare blood cancers than best-sellers in their class. Based on the latest encouraging data, Sierra is now planning to seek FDA approval for its drug momelotinib.
Myelofibrosis is caused by dysregulated signaling in the bone marrow pathway, leading to inflammation and fibrosis, or the accumulation of scar tissue, which impairs red blood cell production. This cancer can cause anemia and require blood transfusions. Myelofibrosis can also lead to an enlarged spleen.Based on preliminary Phase III data report On Tuesday, San Mateo, California-based Sierra Leone reported that momilotinib showed improvement on both issues.
The pivotal study compared Sierra’s drug to danazol, a drug used to treat anemia in patients with myelofibrosis. The study enrolled 195 myelofibrotic anemia patients who had been previously treated with FDA-approved Janus kinase (JAK) inhibitors, a class of drugs that block the JAK enzymes that cause dysregulated signaling at the root of the disease. The primary objective of the study was to measure the proportion of patients who showed a 50% or more reduction in scores according to the Myelofibrosis Symptom Assessment Scale.
According to preliminary data, 25% of patients treated with momotinib met the primary goal, compared with 9% in the control group. Sierra’s drug also outperformed the control group in assessing spleen size and blood transfusion needs, the study’s secondary goals. Sierra’s drug was well tolerated by patients, and fewer adverse events were reported in the momotinib arm than in the control arm. Sierra said the full dataset will be presented at a future medical meeting.
In 2011, the FDA approved the Incyte drug Jakafi, making it the first JAK inhibitor to treat myelofibrosis. In 2019, the FDA approves another drug in this class, Inrebic, from Bristol-Myers Squibb. While these drugs address the JAK mechanism of myelofibrosis, they may also cause or exacerbate myelosuppression—suppression of bone marrow activity resulting in decreased red blood cell production. This feature prevents them from being used as first-line therapy.
Sierra’s momelotinib, also a JAK inhibitor, is designed to block two JAK enzymes and ALK2, which the company says offers a solution to anemia caused by myelofibrosis. An earlier set of Phase 3 studies compared the Sierra JAK inhibitor to Incyte’s drug.According to from Investor introduction. Achieving or maintaining transfusion independence is associated with longer lifespan in patients.
Additional data, reported Tuesday, helps demonstrate momilotinib is a better option for patients than Jakafi, Incyte’s top-selling product across four indications. Being able to provide comparable spleen size control to Jakafi, but also a better response to anemia, could give Sierra’s drug an edge, potentially making it a better choice for patients with anemic myelofibrosis, the company said in the presentation. JAK inhibitors are preferred.
Momilotinib has had several twists and turns on its way to this point. The drug was originally developed by YM Biosciences, which Gilead Sciences acquired in 2012 for $510 million. Gilead advances the molecule to Phase 3 testing, The results were mixed Published in 2016. Although data showed momilotinib was comparable to Jakafi in reducing spleen size and transfusion independence, it did not succeed in meeting that criterion in overall symptom measurement, and Gilead did continue to work on further development of the drug. Sierra acquired momelotinib in 2018 for just $3 million upfront The goal is to test the drug again in Phase 3.
Sierra said in the investor presentation that momilotinib has the potential to become a cornerstone of myelofibrosis treatment. In addition to being used as a monotherapy, the company said the drug could be used as part of a combination therapy with other experimental drugs. Meanwhile, Gilead was able to salvage some of its previous investment in momilotinib. Under the terms of the agreement with Sierra, Gilead will receive up to $195 million in milestone payments as well as royalties on sales if the drug hits the market. Sierra said it plans to submit a New Drug Application to the FDA in the second quarter of this year.
Photos by Flickr users Ed Osman through Creative Commons license
