Alnylam Reports Positive Interim Phase 1 Results for Fitusiran in Hemophilia A and B Patients with Inhibitors
- Once-Monthly, Subcutaneous Fitusiran Achieves Median Annualized Bleeding Rate (ABR) of Zero in this Hemophilia Patient Segment with Highest Unmet Need -
- Fitusiran Generally Well Tolerated with No Thromboembolic Events,
Including with Co-
- Alnylam On Track to Initiate Phase 3 Program in Early 2017 -
- Management to Discuss New Clinical Data in Webcast Conference Call
clinical data showed that once-monthly subcutaneous administration
of fitusiran achieved lowering of AT and increases in thrombin
generation, resulting in a median estimated annualized bleeding rate
(ABR) of zero in patients with hemophilia A or B with inhibitors (N=16).
In addition, fitusiran was generally well tolerated through the data
"As many as one-third of severe hemophilia A patients will develop
inhibitors, one of the most serious treatment-related complications of
hemophilia. We believe that achievement of a median ABR of zero in this
study population is very encouraging, as the prophylactic treatment
options for patients with inhibitors are limited and may be suboptimal
for many patients," said
New results as of an
Fitusiran was generally well tolerated in the study. All adverse events (AEs) were mild or moderate in severity, with the most common AEs consisting of mild injection site reactions (ISRs) in 8 out of 16 patients (50 percent). Asymptomatic and reversible alanine aminotransferase (ALT) increases greater than 3 times the upper limit of normal (ULN), without concurrent elevations in bilirubin greater than 2 times ULN, were observed in three patients, all of whom have medical history of hepatitis C infection (HCV). Non-clinically significant increases in D-dimer were observed in some patients; none were associated with laboratory signs of pathologic clot formation. There were no drug-related serious adverse events (SAEs), no discontinuations due to AEs, and no thromboembolic events through the data cut-off date. All breakthrough bleed events were successfully managed with bypassing agents (recombinant factor VIIa and/or activated prothrombin complex concentrate). As of the data cut-off date, seven inhibitor patients have transitioned to the Phase 2 open-label extension (OLE) study, and continued dosing with fitusiran for up to seven months has been generally well tolerated.
To view the fitusiran clinical results described in this press release, please visit www.alnylam.com/capella.
Conference Call Information
Alnylam management will discuss these clinical data in a webcast conference call tomorrow,
About Fitusiran Phase 1 Study
The ongoing Phase 1 trial of fitusiran is being conducted in
Fitusiran is a subcutaneously administered, investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia A and B and rare bleeding disorders (RBD) currently in early stage clinical development. Fitusiran is designed to lower levels of AT with the goal of promoting sufficient thrombin generation to restore hemostasis and prevent bleeding in patients with hemophilia and RBD. AT, also known as "antithrombin III" and "SERPINC1" is a liver-expressed plasma protein and member of the "serpin" family of proteins that acts by inactivating thrombin and other coagulation factors. AT plays a key role in normal hemostasis by helping to limit the process of fibrin clot formation. However, in hemophilia, insufficient thrombin generation results in impaired fibrin clot formation. Lowering AT in the hemophilia setting may promote the generation of sufficient levels of thrombin needed to form an effective fibrin clot and prevent bleeding. This rationale is supported by human genetic data suggesting that co-inheritance of thrombophilic mutations, including AT deficiency, may ameliorate bleeding in hemophilia. Lowering of AT is a unique and innovative strategy for restoring hemostasis in people with hemophilia. Fitusiran utilizes Alnylam's ESC-GalNAc conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index.
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off 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, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines. Alnylam's pipeline of investigational RNAi therapeutics is focused in 3 Strategic Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline of RNAi therapeutics for the treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics toward genetically validated, liver-expressed disease targets for unmet needs in cardiovascular and metabolic diseases; and Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that address the major global health challenges of hepatic infectious diseases. In early 2015, Alnylam launched its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics as a whole new class of innovative medicines. Specifically, by the end of 2020, Alnylam expects to achieve a company profile with 3 marketed products, 10 RNAi therapeutic clinical programs - including 4 in late stages of development - across its 3 STArs. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Ionis, Novartis, Roche, Takeda,
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including fitusiran, its expectations regarding the timing of clinical studies and the presentation of clinical data, including for its studies of fitusiran, its expectations regarding its STAr pipeline growth strategy, its "Alnylam 2020" guidance for the advancement and commercialization of RNAi therapeutics, and its plans regarding the pursuit of pre-clinical programs and commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its product candidates, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all, actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing, delays, interruptions or failures in the manufacture and supply of our product candidates, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its intellectual property rights against third parties and defend its patent portfolio against challenges from third parties, obtaining and maintaining regulatory approval, pricing and reimbursement for products, progress in establishing a commercial and ex-
The scientific information referenced in this news release relating to
fitusiran is preliminary and investigative. Fitusiran has not been
approved by the
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