We are saddened to inform that Alnylam Pharmaceuticals has reported a fatal thrombotic event in a patient with haemophilia A without inhibitors in the Phase 2 open-label extension (OLE) study of fitusiran.
Fitusiran is an RNAi therapeutic in development for the treatment of haemophilia A and B with or without inhibitors.
Please find Alnylam’s statement below:
- Company Suspends Fitusiran Dosing due to Thrombotic Event and Aims to Resume Dosing as Soon as Possible upon Agreement with Global Regulatory Authorities
CAMBRIDGE, Mass.–(BUSINESS WIRE)– Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY), the leading RNAi therapeutics company, announced today an update on the company’s fitusiran and givosiran investigational RNAi therapeutic programs. With fitusiran, an RNAi therapeutic in development for the treatment of hemophilia A and B with or without inhibitors, Alnylam is reporting a fatal thrombotic event in a patient with hemophilia A without inhibitors in the Phase 2 open-label extension (OLE) study of fitusiran. As a result, the Company has suspended dosing in all ongoing fitusiran studies pending further review of the safety event and development of a risk mitigation strategy. Based on overall consideration of fitusiran’s benefit-risk profile, Alnylam is guiding that it aims to resume dosing as soon as possible upon agreement with global regulatory authorities and with appropriate protocol amendments in place for enhanced patient safety monitoring.
Fitusiran Program Update
“We are deeply saddened to learn of this patient’s death, and we extend our sympathies to his family,” said Akshay Vaishnaw, M.D., Ph.D, Executive Vice President of R&D at Alnylam. “We believe that fitusiran holds great promise as a potential treatment option for patients with hemophilia, and we remain fully committed to its ongoing development. Following further investigation of this safety finding, implementation of a risk mitigation strategy, and alignment with global regulatory authorities, we expect to resume fitusiran dosing in our clinical studies as soon as possible, potentially as early as late 2017, with a goal of advancing this innovative investigational medicine to hemophilia patients in need.”
Fitusiran clinical studies include the ongoing Phase 2 OLE study of hemophilia A and B patients with and without inhibitors and the ATLAS Phase 3 program, which has recently been initiated but in which patient dosing has yet to begin. Alnylam recently became aware of a fatal serious adverse event (SAE) that occurred in a patient with hemophilia A who was receiving fitusiran in the Phase 2 OLE study. Approximately nine days prior to hospital admission, he developed exercise-induced right hip pain that was treated with a total of three doses of factor VIII concentrate (31-46 IU/kg) on three separate days. Four days prior to admission, when the patient received his third dose of factor, he developed a severe headache. While he was initially suspected of having viral meningitis, the patient was diagnosed with subarachnoid hemorrhage on the basis of CT imaging, and treated with factor VIII concentrate administered two to three times daily. Over a 14-day hospitalization, his medical condition worsened despite the administration of factor and the patient died from subsequent cerebral edema. The initial diagnosis of subarachnoid hemorrhage was reported by the investigator as not related to fitusiran. For a more complete understanding, the Company initiated further investigation of the SAE, including review of the patient’s CT scans by three independent neuro-radiologists, who all confirmed on September 1, 2017, that the initiating event was a cerebral venous sinus thrombosis, and not a subarachnoid hemorrhage. As a result of this new information, Alnylam suspended dosing in fitusiran studies in order to further investigate the safety event, now considered to be possibly related, and to develop a risk mitigation plan. The Company also notified study investigators and global regulatory authorities.
Fitusiran is an investigational, once-monthly, subcutaneously administered RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia A and B, with and without inhibitors. Fitusiran also has the potential to be used for rare bleeding disorders. Fitusiran is designed to lower levels of AT with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding. Fitusiran utilizes Alnylam’s ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability. The clinical significance of this technology is under investigation.
The safety and efficacy of fitusiran have not been evaluated by the FDA, the EMA or any other health authority.
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding protein synthesis in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, with the goal of preventing disease-causing proteins from being made.
* The complete statement can be found on Alnylam’s website: http://investors.alnylam.com/releasedetail.cfm?ReleaseID=1039464
The EHC expresses condolences to the family and friends.