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(This roundup of news from the ASH 2024 conference first appeared in STAT’s “ASH in 30” newsletter. Sign up here to receive future editions.)
Greetings from always beautiful San Diego. Adam Feuerstein, here, and as you can see in the sunrise photo above, I’m still very much on East Coast time. (Nice view from my hotel room, though.) I’ve traveled a long way to bring you news and analysis from the annual meeting of the American Society of Hematology. And I’m not the only one! Joining me are fellow STAT reporters (and all West Coast residents) Jonathan Wosen, Angus Chen and Meghana Keshavan. Let’s roll.
Sanofi is developing a new treatment for a rare, platelet-destroying disease
An oral treatment developed by French pharmaceutical giant Sanofi increased platelet counts and reduced bleeding episodes in patients with a rare autoimmune disease that causes the body to attack and destroy its own blood-clotting platelets.
In a randomized phase 3 trial, the Sanofi drug called rilzabrutinib achieved improved platelet response in 65% of participants with persistent or chronic immune thrombocytopenia (ITP), compared with 33% of participants on placebo. Durable platelet response was reported in 23% of the rilzabrutinib group, compared with no patients in the control arm. The drug also showed a reduction in the number of bleeding episodes and improvements in fatigue.
Rilzabrutinib is a Grossen’s kinase (Btk) inhibitor, a type of drug approved for use in treating blood cancers. But rilzabrutinib appears to be safer and better tolerated than existing drugs in the class, says David Kuter, physician and director of hematology at Massachusetts General Hospital, and an investigator in the Sanofi study.
Many patients with severe ITP experience temporary benefits from currently available treatments or do not respond at all. The durability of platelet responses seen with rilzabrutinib could help establish the drug as a new standard of care, Kuter added.
Sanofi has submitted rilzabrutinib to regulators in the US and Europe, with a decision on potential US approval expected in August next year.
A Novo Nordisk pill appears to reduce severe sickle cell pain crises
An oral drug from Novo Nordisk appeared to improve the oxygen-carrying ability of red blood cells and reduce the frequency of severe pain crises in patients with sickle cell disease. The results of the Phase 2 trial, if confirmed in a larger study, could lead to a new way to treat the debilitating blood disease that mainly affects people of African descent, including Black Americans.
Sixty participants took part in the study and experienced an average of 3.3 severe pain crises per year. After one year of the study, the number of annual pain crises dropped to just over one for participants treated with Novo’s once-daily pill called etavopivat, compared with just under two for participants given a placebo.
Statistically, etavopivat reduced the occurrence of pain crises by 46% compared to placebo, although the improvement did not reach statistical significance. Etavopivat also increased levels of hemoglobin, the protein that helps red blood cells carry oxygen, and improved levels of fatigue, both compared with placebo. Headache, stomach upset and elevated liver enzymes were the most commonly reported side effects.
Etavopivat belongs to a class of drugs that activate an enzyme called pyruvate kinase, which is used by red blood cells to convert sugars into energy. The drug improves the health of red blood cells and slows their destruction.
“These results are encouraging,” said Julie Kanter, physician and director of the adult sickle cell program at the University of Alabama at Birmingham. Kanter was an investigator in the etavopivat trial and sees that the drug, if ultimately approved, has the potential to become a standard treatment for the disease, alongside mainstream medications such as hydroxyurea.
Novo is conducting a larger Phase 3 trial of etavopivat in sickle cell disease, with results expected in 2026. Agios Pharmaceuticals is developing a similar drug, called mitapivat, also in a late-stage clinical trial.
The US regulatory barrier to approving new drugs to treat sickle cell disease has likely increased following the recent withdrawal from the market of Pfizer’s sickle cell drug Oxbrytra due to safety concerns. With Oxbryta, the FDA has relaxed its standard and granted approval based on an improvement in hemoglobin levels alone.
Kanter said she would like to see drugmakers design sickle cell disease studies that use patient-reported outcomes, including but not limited to severe pain crises, as a more meaningful measure of overall patient benefit.
Rating a drug solely based on the frequency of severe pain crises that send someone to the hospital is difficult to standardize because individuals have different levels of pain tolerance or access to medications and hospitals to treat pain, Kanter said.
Beam’s CRISPR therapy for sickle cell disease is delivering consistent results in more patients
In more sickle cell news, seven patients treated with a CRISPR-based therapy from Beam Therapeutics all produced more than 60% fetal hemoglobin, a healthy, normally functioning form of the oxygen-carrying molecule. The corresponding levels of sickle-shaped, or disease-causing, hemoglobin in the blood of all seven patients fell below 40%, Beam reported today.
No patients have reported severe pain crises since treatment with the Beam therapy, called BEAM-101, although follow-up time remains relatively short.
The updated study results are consistent with an analysis conducted in four patients reported in November.
BEAM-101 uses a newer, gentler form of CRISPR called basic editing. Basic editing only “nicks” the DNA and changes a single letter, rather than breaking an entire gene. The base-editing approach could lead to healthier cells and higher levels of fetal hemoglobin, compared to an older version of CRISPR used by Vertex Pharmaceuticals in its approved treatment called Casgevy.
As previously reported, a participant in the Beam study died due to respiratory failure caused by the toxic chemotherapy regimen needed to prepare the bone marrow before BEAM-101 can be administered.
Many sickle cell patients with serious disease struggle with a heartbreaking dilemma: potentially curative therapies carry the risk of infertility because of the treatment regimens that precede these therapies. New research presented at ASH underlines that, in the hands of experienced healthcare providers, fertility preservation before curative therapy is a viable option for patients – provided they have access to the procedure.
Researchers reviewed the medical records of sickle cell patients at five treatment centers seeking egg cryopreservation, in which a doctor uses hormones to coax the ovaries to release immature eggs, or eggs, which are then extracted and frozen. Of the 45 patients, 36 required only a single cycle, while five required at least two hormone cycles due to low cell yield the first time.
The researchers also saw that patients generally required higher levels of the hormone gonadotropin to stimulate their ovaries compared to other young adults who underwent the procedure, and yet the ovaries of people with sickle cell disease still responded less to the hormone. But the number of eggs retrieved and stored was similar between people with and without the disease.
Nearly half of cryopreservation cycles were associated with a complication, including 19 cases of pain crises after egg retrieval. Researchers found that the risk of a complication was significantly higher in patients who had had at least three pain crises in the previous year.
“We can make this a safe procedure, not to say that there won’t be complications like pain and repeated cycles,” said Marti Goldenberg, a pediatric hematologist at Johns Hopkins and the study’s first author. “This can be a great option for patients, as long as they get counseling.”
A bigger challenge, she added, is that only 21 states have laws requiring insurers to cover fertility services. With the arrival of gene therapies from Vertex and CRISPR Therapeutics and Bluebird Bio, more sickle cell patients will likely turn to these services. Vertex filed a lawsuit against the U.S. government earlier this year to allow the company to pay for fertility preservation services for people who receive the therapy, a move that currently risks violating federal law.