Results from a small study of hemophilia patients published in The New England Journal of Medicine suggest a drug being developed by the French pharmaceutical giant Sanofi could challenge market-leading treatments for the rare bleeding disorder.
Hemophilia patients lack certain proteins needed to clot blood. In the more common, hemophilia A form, the missing protein is called Factor VIII. People without this disorder typically have around 100% Factor VIII levels, though anywhere between 50% and 150% is considered "normal." Having less than 1% the normal amount of protein is a sign of severe hemophilia.
People with severe hemophilia A typically use injectable drugs multiple times a week to replace the clotting proteins they lack. Sanofi has been developing a longer-lasting version, meant to be used once weekly or less, that it acquired when it bought Bioverativ in 2018.
Last year it produced the first significant results from that program, a study that looked at 16 men with severe hemophilia A. Patients who received a high dose of the company's drug, BIVV001, had Factor VIII levels at 38% five days after treatment. At day seven, average levels were still at 17%.
New details unveiled Thursday in NEJM show those patients' protein levels were in normal range through day four. Study authors wrote these results imply Sanofi's drug could be given on a weekly interval, which would be longer than most of the currently available hemophilia therapies. In fact, the time it took for patients' bodies to go through half of BIVV001 was about 43 hours, or three to four times longer than so-called recombinant Factor VIII drugs.
"This effect would transform severe hemophilia A into a mild disease," Pier Mannucci, a researcher who currently sits as chairman of the Department of Internal Medicine and Medical Specialties at the University of Milan, wrote in an editorial accompanying the published data.
Sanofi's drug also appeared to be safe. No patient developed inhibitors — a type of antibody that attacks replacement clotting protein and is a major concern for hemophilia patients. Researchers also didn't see overactive immune responses or anaphylactic events in the month after patients were treated.
The BIVV001 data come during a renaissance period for hemophilia drug research. Companies are working on more durable medicines that could revolutionize care both for patients and for the healthcare system.
"Overall, as a long-standing insider of hemophilia care amid lights and shadows, I am impressed by the amazing progress that is still occurring in the management of this ancient scourge," Mannucci wrote.
Gene therapy, in particular, has attracted attention for its potential to effectively cure the disease. BioMarin looked as though it would secure the first ever Food and Drug Administration approval of a hemophilia gene therapy last month. But in a shocking twist, the agency said it needed more data before it could clear the treatment, known as Roctavian, for use.
BioMarin won't have the data required to meet the agency's request until the tail end of 2021.
The company disclosed this week that it's run into a delay in Europe as well. Regulators there want one year's worth of data for all patients in a large, ongoing clinical trial who are receiving a high dose of Roctavian. BioMarin said completing that request won't be possible until this November.
As BioMarin sorts out those data challenges, other gene therapies and longer-lasting therapies are inching closer to market. Sanofi, for example, has already kicked off a larger study of BIVV001.
If Sanofi can replicate the findings from the smaller trial, it could set up BIVV001 not just for approval, but to become "the first choice among factor VIII replacement products administered intravenously because of the reduction of the dosing frequency," Mannucci wrote.
BIVV001 may also, according to Mannucci, provide a competitive threat to Hemlibra, a market-leading hemophilia A drug from Roche that is given once weekly and, sometimes, once monthly.
Overcoming Hemlibra might be difficult, however. In the first half of 2020, Roche recorded Hemlibra sales of just over 1 billion Swiss francs. After less than three years on market, Hemlibra has taken 23% of total U.S. patient share, according to Roche.