A drug abandoned by Gilead Sciences is turning out to have much better prospects under Sierra Oncology. A growing slate of pivotal clinical data support the small molecule’s case as a better treatment choice for a rare blood cancer compared to a blockbuster seller in the same drug class. Based on the the latest encouraging data, Sierra is now planning to seek FDA approval of its drug, momelotinib.

Myelofibrosis is caused by dysregulated signaling in the pathways in bone marrow, leading to inflammation and fibrosis, or a buildup of scar tissue, which impairs the production of red blood cells. This cancer can cause anemia that requires treatment with blood transfusions. Myelofibrosis can also lead to an enlarged spleen. According to the preliminary Phase 3 data reported by San Mateo, California-based Sierra on Tuesday, momelotinib showed improvements on both of those problems.

The pivotal study compared Sierra’s drug to danazol, a drug used to treat anemia in myelofibrosis patients. The study enrolled 195 myelofibrosis patients with anemia who had previously been treated with an FDA-approved Janus kinase (JAK) inhibitor, a class of drugs that block the JAK enzymes that cause the dysregulated signaling at the root of the disease. The study’s main goal was to measure the proportion of patients who showed a 50% or greater reduction in score according to a myelofibrosis symptom assessment form.

According to the preliminary data, 25% of patients treated with momelotinib met the main goal compared to 9% in the control group. Sierra’s drug also bested the control group on the study’s secondary goals assessing spleen size and the need for blood transfusions. The Sierra drug was well tolerated by patients, and fewer adverse events were reported in the momelotinib group compared to the control arm. Sierra said that the complete dataset would be presented at a future medical meeting.

In 2011, the FDA approved Incyte drug Jakafi, making it the first JAK inhibitor for treating myelofibrosis. In 2019, the FDA approved another drug in the class, Inrebic, from Bristol Myers Squibb. While these drugs address the JAK mechanism underlying myelofibrosis, they can also cause or worsen myelosuppression—a tamping down of the bone marrow activity that results in reduced red blood cell production. That feature prevents them from being used as first-line therapies.

Sierra’s momelotinib is also a JAK inhibitor, designed to block two JAK enzymes as well as ALK2, which the company said offers a way to address anemia caused by myelofibrosis. An earlier set of Phase 3 studies compared the Sierra JAK inhibitor to Incyte’s drug. Head to head, Sierra’s drug led to a better increase in hemoglobin as well as a reduction in the need for a blood transfusion, according to data from an investor presentation. Achieving or maintaining transfusion independence was associated with improving how much longer patients live.

The additional data reported Tuesday help build the case that momelotinib is a better option for patients compared to Jakafi, which is a blockbuster seller for Incyte across four indications. The ability to offer comparable spleen size control to Jakafi but also offer a better anemia response could give Sierra’s drug an edge, potentially making it the JAK inhibitor of choice for anemic myelofibrosis patients, the company said in the presentation.

Momelotinib’s path to this point has had several twists and turns. The drug was initially developed by YM Biosciences, which Gilead Sciences acquired in 2012 for $510 million. Gilead advanced the molecule to Phase 3 testing, with mixed results posted in 2016. Though the data showed that momelotinib was comparable to Jakafi in reducing spleen size and in transfusion independence, it did not successfully meet that mark in the measure of total symptoms and Gilead did continue to work on further pursue the drug. In 2018, Sierra paid just $3 million up front to acquire momelotinib with the goal of testing the drug again in Phase 3.

In the investor presentation, Sierra said momelotinib has the potential to become the cornerstone of myelofibrosis treatment. In addition to its use as a monotherapy, the company said that the drug could be used as part of combination therapies with other experimental drugs. Meanwhile, Gilead is able to salvage some of what the investment it had previously made in momelotinib. Under the terms of the agreement with Sierra, Gilead is in line to receive up to $195 million in milestone payments plus royalties from sales if the drug reaches the market. Sierra said it plans to submit a new drug application to the FDA in the second quarter of this year.

Photo by Flickr user Ed Uthman via a Creative Commons license