But toxicology and safety assessments conducted by the company found that the benefit-risk profile of the product remains unchanged.
Hemlibra is a bispecific factor IXa– and factor X–directed antibody that has beenin the United States and other countries for routine prophylaxis in adult and pediatric patients with hemophilia A, with or without factor VIII inhibitors. It is administered as a subcutaneous injection.
The particles were first identified in March 2019 during a routine examination of drug product batches by. At the time, the company informed the U.S. Food and Drug Administration; the European Medicines Agency; Swissmedic; Health Canada; and the Ministry for Health, Labour, and Welfare in Japan. An initial company assessment found that the particles consisted of protein (Hemlibra drug substance) and silicone oil (polydimethylsiloxane), an organic polymer included in all parenteral medicines, according to Genentech.
Since the health authorities all agreed with the company’s initial conclusion that the product’s safety remained unchanged, no further action was taken.
The presence of the particles became more widely known in early October 2019, when Genentech notified the National Hemophilia Foundation, the NHF’s Medical and Scientific Advisory Council (MASAC), and the Hemophilia Federation of America. Genentech officials reached out to these groups after finishing a root cause investigation and issuing a final report to health authorities concluding that there was no change in the benefit-risk profile, according to a company spokesman.
MASAC issued its ownrecommending no change in prescribing or interruption in the use of Hemlibra. This is an “interim recommendation pending our assessment of the full review by Roche/Genentech of their manufacturing and quality control,” MASAC said. The council noted that it had been informed by representatives from Roche/Genentech that there have been no reports of adverse events linked to the particulate matter. Additionally, the problem had been present since the initial clinical trials of the product, but was only recently identified.
But at least one patient advocate is raising concerns about the timing of this notification. Jesse Clark, president and CEO of, wants to know why patients were not informed of the particle issue for more than 6 months.
“The bleeding disorder community was never notified by either Genentech or any other agency,” Mr. Clark said in an interview. “The lack of transparency and communication is extremely concerning.”
A spokesman for Genentech said the company had not alerted patients earlier because there was no indication of an impact on the safety of the product. “We take inquiries from the community very seriously and are providing context and additional details in response to requests from patient organizations,” he said in an interview.
The company does not expect this issue to impact any patients in the United States and the availability of Hemlibra will not be affected, he added.