After two hemophilia patient groups broke the news earlier this week that five patients taking Roche’s new drug Hemlibra had died, the drugmaker quickly responded that the deaths were not related to the drug. Still, concerns arose on Wall Street that the news could stifle growth of the key product, which analysts had expected to rake in $4 billion or more in sales by 2022.
Now Roche is providing more details about exactly what happened to those patients.
"Since 2016, five adults with hemophilia A with inhibitors taking Hemlibra have passed away. In each of these cases, the assessment of the treating physician or investigator was that the cause of death was unrelated to Hemlibra," a spokeswoman for the company said in an email to FiercePharma.
Three of the deaths were in patients receiving the drug under a compassionate-use program, according to the company. In 2016, one of those patients died “due to an intracranial hemorrhage and widespread bacterial infection,” which a doctor determined to be unrelated to the drug. Last year, another patient who had suffered intracranial hemorrhages before starting the drug had another after taking Hemlibra; it also was deemed unrelated to the drug.
A third patient who died had been a participant in the phase 3 HAVEN 1 trial. That death was blamed on a rectal hemorrhage, not on Hemlibra.
The spokesperson said Roche recently learned that another patient who had been taking the drug under compassionate use had “an abdominal pseudo-tumor” and died of complications of that condition, according to the statement.
A fifth patient taking Hemlibra passed away after undergoing major vascular surgery, the company said. Roche undertakes "rigorous assessment and reporting protocols" upon learning of patient deaths, and the assessment of the two most recent cases is ongoing, the spokesperson said. "We understand the urgency of reviewing and assessing safety events, and it is a priority for us to share accurate information about the safety of Hemlibra that is based on a thorough assessment."
Still, safety concerns were already high, as the company had previously reported incidences of thrombosis—blood clots—and when the drug was approved by the FDA in November, it included a black box warning about the risk.
The news about the recent Hemlibra patient deaths came just days after Clarivate Analytics named the drug one of 12 to watch this year. “Hemlibra will challenge standard-of-care factor VIII replacement therapy with its novel action, impressive efficacy and potential monthly dosing,” the report raved. It added that even with the black box warning, “the treatment is set to lead the market from 2020 onwards.”
But safety worries could very well hamper Roche’s ability to reach the high end of the sales forecasts for Hemlibra, which hinge on the company getting the label expanded for patients who don’t have antibodies to factor VIII. A phase 3 trial in that patient group turned in positive data late last year.
The marketing challenge will be compounded by competition, primarily from Shire, which has two older treatments on the market, Feiba and Advate. The entry of Hemlibra initially prompted Shire analysts to project steep declines for Shire’s hemophilia stalwarts—but now some are wondering whether they jumped the gun on the assumption that Roche’s newcomer would be embraced by physicians and patients.
Jefferies analyst David Steinberg had been assuming that sales of Feiba would decline 50% over five years and that Advate sales would drop 25%, but “if any material concerns reemerge about Hemlibra’s safety, changes regarding the erosion curve dynamics could have a very significant impact on” Shire, he wrote in a report earlier this week.