- Roche AG this week informed physicians and hemophilia advocacy groups in the U.S. that a total of five patients with hemophilia A have died since 2016 while on treatment with the Swiss pharma's newly approved drug Hemlibra.
- Three of the cases were previously reported and all were judged to be unrelated to Hemlibra by the treating physician or investigator, according to Roche. Still, the update stirred worries around the drug's safety profile, initially weighing on shares of Roche during Wednesday trading on the Swiss stock exchange.
- Hemlibra, approved for a subgroup of sicker hemophilia A patients in the U.S. late last year, is a key drug for Roche and looks set to shake up the current treatment landscape for the blood disorder with strong efficacy and greater convenience.
Roche said it had recently learned of the two new cases, both of which involved the death of an adult patient receiving Hemlibra (emicizumab-kxwh). One patient received treatment through a request for compassionate use, while the other was participating in an expanded access program in the U.S.
"We have, and will continue to, provide timely and transparent updates on Hemlibra's safety to health authorities, healthcare professionals and the hemophilia community," Roche said in an emailed statement. "If any adverse event in a person taking Hemlibra impacts the overall benefit/risk profile of the medicine, we will share this information as quickly as possible."
Safety issues for Hemlibra have sparked concern in the past, and the Food and Drug Administration required the drug carry a black box warning on the risk of thrombotic microangiopathy and thromboembolism.
Given the severe condition of hemophilia patients for whom Hemlibra is approved, however, it's not uncommon for deaths to occur despite treatment for uncontrolled bleeds.
"I think it is really hard to interpret. These are sporadic cases in probably extenuating circumstances," said Michael Callaghan, a physician and assistant professor of pediatrics at Wayne State University School of Medicine, in an interview.
"Without knowing the denominator of how many [patients] are on the drug for how long, it is hard to say if this is more or less severe events than you'd expect."
Hemlibra is currently OK'd in the U.S. and Europe for only those hemophilia A patients who have developed antibodies that prevent Factor VIII medicines from working properly — a sicker population with few other treatment options.
Roche hopes, however, to soon expand the market for Hemlibra to patients without inhibitors. Topline results from a study known as HAVEN 3, released in December, showed preventive treatment with the drug significantly reduced the number of treated bleeds compared to no prophylaxis. Roche expects to file for U.S. and EU approval later this year.
Yet in the broader non-inhibitor patient population, safety issues could become a larger issue.
"Despite what will likely be rapid uptake in the inhibitor population these safety concerns could meaningfully slow or prevent uptake in the larger and very well controlled non-inhibitor patients," wrote Cowen & Co. analyst Ken Cacciatore in a March 28 note on rival Shire plc's hemophilia business.
Shares in Roche quickly recovered from early trading losses, and were up more than 1% late in the day on the Swiss exchange.
A legal decision in Japan may have contributed to the recovery, with a Tokyo district court ruling Hemlibra does not infringe patents held by subsidiaries of hemophilia competitor Shire plc.