Patients with polycythemia vera (PV), a rare cancer characterized by overabundant red blood cells, have endured years of middling progress in their therapeutic options. But the tide may finally be turning in their favor, as Merck & Co. and Takeda both presented new data on their different approaches for the disease at the American Society of Hematology (ASH) conference in Orlando, Florida.
“Polycythemia vera is a condition that, unfortunately, has not had a lot of therapeutic advances over the past few decades,” Gregory Lubiniecki, M.D., vice president of global development at Merck Research Laboratories, told Fierce at ASH. The first drug specifically approved for PV was Incyte’s JAK inhibitor Jakafi (ruxolitinib), which earned the nod in 2014.
Dec. 6, Merck presented the first data from a phase 2 study of bomedemstat, an oral lysine-specific demethylase 1 (LSD1) inhibitor the pharma picked up through its $1.4 billion buy of Imago BioSciences back in 2022.
In the Shorespan-004 trial, patients took bomedemstat daily for 36 weeks, with some patients continuing on for a total treatment period of 52 weeks. Of the 20 patients enrolled, nine achieved blood cell counts that were below 45% of their baselines by Week 36 without needing to have blood drawn, the trial’s primary endpoint.
Patients with PV frequently require blood drawing, or phlebotomy, to relieve their bodies of excess blood cells.
However, the sample size was too small for Merck to analyze the endpoint for statistical significance, Lubiniecki explained.
Merck’s trial focused on patients whose disease had not been helped by established treatments like hydroxyurea or interferon therapies such as PharmaEssentia’s Besremi (ropeginterferon alfa-2b). Lubiniecki referred to the side effect profile as “manageable for patients.” Eight of the 20 patients discontinued treatment, including one who died from a hemorrhagic stroke that was not related to bomedemstat, according to the presentation.
Stroke is a common complication of PV, as are dangerous blood clots that can lead to embolisms and heart failure.
In all, 40% of patients experienced a serious adverse event, though none of the patients who discontinued treatment did so because of treatment-related adverse events.
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Merck is currently analyzing additional data from the trial, which it plans to share at a future medical meeting, while also weighing whether to pursue further development of bomedemstat in PV, Lubiniecki said.
Even if the New Jersey pharma giant decides not to move forward in PV, the company is currently trialing bomedemstat in two phase 3 studies for essential thrombocythemia, a related disease.
Those trials are “going well, and the studies are accruing,” Lubiniecki said. “There’s excitement in the community about them.”
Takeda’s victory lap
Takeda, meanwhile, took to the ASH stage Dec. 6 to share updated data from the phase 3 Verify trial of Protagonist Therapeutics-partnered rusfertide, a once-weekly self-given injection. The Japanese pharma announced in March that rusfertide had hit its primary endpoint, with 77% of patients given the molecule not requiring phlebotomy across weeks 20 to 32 of treatment.
Now, Takeda has presented data up to 52 weeks, showing that 77.9% of patients given rusfertide didn’t need phlebotomies between weeks 40 and 52.
But, while hitting primary endpoints is always nice, Takeda oncology head P.K. Morrow, M.D., is most excited by rusfertide’s ability to improve patients’ quality of life.
Rusfertide was “able to relieve symptoms which patients care so deeply about,” Morrow told Fierce at ASH, such as fatigue and brain fog.
“Many patients and physicians are asking for a better understanding of not just efficacy, but also the relief of symptoms,” she said. “That’s where I think the field is continuing to move.”
Takeda has had “collaborative discussions” with the FDA regarding rusfertide, and it plans to submit the candidate for approval by the end of March 2026.
“We are encouraged to see how the PV landscape is seeing meaningful improvements,” analysts from BMO wrote Dec. 8. The analysts deemed bomedemstat “interesting” but “too nascent” to fully assess at this stage.
As for Takeda’s drug, the analysts said physicians are “looking to rusfertide as a new standard of care.”
Though bomedemstat and rusfertide are both designed to alleviate elevated blood cell counts in PV, they have different mechanisms of action and potential uses in treatment, Lubiniecki explained.
Bomedemstat is designed to inhibit LSD1, a key enzyme in regulating the reproduction and maturation of blood stem cells in bone marrow. Rusfertide, meanwhile, mimics the function of hepcidin, a naturally occurring protein that regulates iron levels in blood.
“Rusferitide is really more of a supportive care type of therapy for patients who have polycythemia vera and bomedemstat is being used as a cytoreductive agent similar to hydroxyurea,” Lubiniecki said.
In theory, if both were approved, physicians could use them together. “They would not be exclusive,” the Merck Research Laboratories exec said.
