The archaic observe of eradicating blood from the physique to deal with a variety of diseases lives on immediately as a typical therapy for sure blood issues. The fashionable model of this strategy, referred to as therapeutic phlebotomy, can handle these situations however nonetheless comes with limitations and complication dangers. A drug from companions Protagonist Therapeutics and Takeda Pharmaceutical gives the promise of a therapeutic intervention for one in every of these uncommon blood illnesses, polycythemia vera.
One-year information for the drug, rusfertide, have been offered Saturday in the course of the annual assembly of the American Society of Hematology in Orlando, Florida. Past exhibiting the overwhelming majority of research members reached a degree the place they not wanted phlebotomy, outcomes additionally confirmed enhancements on high quality of life measures, such because the persistent fatigue that’s the commonest criticism of polycythemia vera sufferers, mentioned Dr. Andrew Kuykendall, affiliate member within the division of hematology at Moffit Most cancers Middle and lead investigator in rusfertide’s pivotal research.
“There may be this want to maneuver past, transfer out of the darkish ages to some extent, and change therapeutic phlebotomy with one thing else that may reliably keep and management blood cell counts within the secure vary with out actually exacerbating iron deficiency and (additionally) selling symptom enchancment,” Kuykendall mentioned in an interview.
Polycythemia vera is a uncommon blood most cancers that results in overproduction of purple blood cells. Consequently, blood turns into thicker and clots extra simply, placing sufferers in danger for cardiovascular occasions equivalent to coronary heart assault or stroke. Therapeutic phlebotomy brings purple blood cell counts nearer to regular ranges however requires common scientific visits for the process. Opposed results embody fluid shifts within the physique that depart sufferers feeling dizzy, Kuykendall mentioned. Therapeutic phlebotomy additionally exacerbates the iron deficiency that these sufferers have already got as a result of the physique is utilizing iron to make purple blood cells.
In an interview earlier this yr, Takeda President of Analysis & Improvement Andrew Plump described therapeutic phlebotomy as “very medieval.” Moreover, whereas it’s may be efficient, over time, many sufferers who routinely bear this process develop iron deficiency. Rusfertide is a peptide that Protagonist designed to face in for hepcidin, a hormone that regulates how iron is absorbed, saved, and distributed within the physique.
“Principally what it’s doing is it’s trapping iron in its pure shops and making it much less accessible to the bone marrow,” Plump mentioned. “So it’s decreasing manufacturing of purple blood cells. It’s a really physiologically related pathway, and what we’ve seen in Section 2b (scientific testing) is actually functionally curing (of) these sufferers.”
The placebo-controlled Section 3 take a look at of rusfertide evaluated 293 sufferers with polycythemia vera over the course of 156 weeks. Knowledge from the primary 32 weeks, which confirmed 76.9% of sufferers achieved a scientific response, have been offered earlier this yr in the course of the annual assembly of the American Society of Medical Oncology.
The most recent information offered on the ASH assembly are from sufferers who’ve acquired the once-weekly injectable drug for 52 weeks. These outcomes present 61.9% of sufferers handled with rusfertide continued to not want phlebotomy. The research drug was secure and nicely tolerated. The commonest antagonistic results have been injection website reactions, anemia, and fatigue.
Few medication can be found for polycythemia vera. Drugs used to cut back blood counts are one choice for many who can’t tolerate phlebotomies. Incyte’s oral small molecule Jakafi, which was initially permitted in 2011 for myelofibrosis, expanded its FDA approval to polycythemia vera in 2014. On this indication, the Incyte drug is permitted as second-line choice for a slim section of sufferers, Kuykendall mentioned. PharmaEssentia’s Besremi, permitted by the FDA in 2021, gives a first-line therapy selection. This drug is an engineered model of interferon alfa, a protein that prompts and regulates the immune response.
Interferon medication aren’t used for sufferers with a historical past of temper issues or these with a historical past of autoimmune situations, Kuykendall mentioned. It additionally takes time for interferon medication to work, and even once they work in polycythemia vera, sufferers should still want phlebotomies to take care of illness management. That leaves an unmet want for sufferers who can’t tolerate present medication or want higher illness management, he mentioned.
Final yr, Takeda paid $300 million to start a partnership with Protagonist. Newark, California-based Protagonist remains to be liable for the Section 3 research and an FDA submission; the 2 firms will share in U.S. commercialization of the drug. The deal gave Takeda the rights to commercialize rusfertide in the remainder of the world. With the optimistic Section 3 outcomes now accessible, Protagonist and Takeda mentioned they’re making ready a regulatory submission for the drug.
Picture: virusowy, Getty Photos
