Alnylam Initiates Fitusiran (ALN-AT3) Dosing in Hemophilia A and B Patients with Inhibitors in Ongoing Phase 1 Study
- Company Reinforces Global Commitment to Patients with Hemophilia During Bleeding Disorders Month -
- Fitusiran Phase 3 Initiation Remains on Track for Mid-2016 -
"As many as one third of people with hemophilia develop inhibitory
antibodies and become refractory to their replacement factor therapy. As
a result, their clinical course becomes more difficult to manage and
these patients generally have poorer clinical outcomes," said
"In recognition of Bleeding Disorders Month, we are pleased to
demonstrate our continued commitment to people with hemophilia by
advancement of our fitusiran study in inhibitor patients," said
About the Fitusiran Phase 1 Study
The ongoing Phase 1 trial of fitusiran is being conducted in
Fitusiran is an investigational compound, currently in early stage
clinical development. The safety and efficacy of fitusiran have not been
evaluated by the
Fitusiran Clinical Data
Clinical data from the ongoing Phase 1 clinical study with fitusiran
were presented at the
- Fitusiran achieved potent, dose-dependent, and statistically significant lowering of AT of up to 88 percent in patients with hemophilia. In addition, AT lowering was associated with statistically significant and clinically meaningful increases in thrombin generation and, in an exploratory post-hoc analysis, was associated with statistically significant decreases in bleeding frequency.
- In another post-hoc analysis, there was an 85 percent reduction in median estimated annualized bleeding rate (ABR) during the observed period of fitusiran administration, as compared with median historical on-demand ABR in nine evaluable patients.
Fitusiran was found to be generally well tolerated through the data
cutoff date of
November 12, 2015, including no serious adverse events, discontinuations or thromboembolic events, no clinically significant changes in laboratory parameters or clinically significant increases in D-dimer, a biomarker of excessive clot formation. Three reported drug related adverse events were all mild, including two transient injection site reactions. Not related to fitusiran, one patient was hospitalized due to reactivation of hepatitis C.
As noted above, and consistent with previous guidance, the Company expects to report additional safety and clinical activity data from the Phase 1 study in mid-2016 and again in late 2016.
Also at the 2015 ASH conference, Alnylam and collaborators presented pre-clinical data demonstrating that AT lowering in vitro led to increased thrombin generation in plasma from patients with hemophilia who have developed inhibitory antibodies to replacement factor therapy.
The clinical and pre-clinical datasets described above can be accessed at www.alnylam.com/capella.
About Hemophilia and Rare Bleeding Disorders
Hemophilia is a bleeding disorder characterized by insufficient thrombin
generation following hemostatic challenge and resulting in recurrent
bleeds into joints, muscles, and other internal organs. Hemophilia A is
defined by loss-of-function mutations in Factor VIII, and there are
greater than 40,000 registered persons in the
About Antithrombin (AT)
Antithrombin (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.
In January 2014, Alnylam and Sanofi Genzyme, the specialty care global
business unit of Sanofi, formed an alliance to accelerate and expand the
development and commercialization of RNAi therapeutics across the world.
The alliance is structured as a multi-product geographic alliance in the
field of rare diseases. Alnylam retains product rights in
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, Merck, Monsanto, The
Medicines Company, and Sanofi Genzyme. In addition, Alnylam holds an
equity position in Regulus Therapeutics Inc., a company focused on
discovery, development, and commercialization of microRNA therapeutics.
Alnylam scientists and collaborators have published their research on
RNAi therapeutics in over 200 peer-reviewed papers, including many in
the world's top scientific journals such as Nature, Nature Medicine,
Nature Biotechnology, Cell,
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, expectations regarding the reporting of data from its Phase 1 clinical trial with fitusiran, expectations regarding the timing for initiation of two Phase 3 trials with fitusiran, the expected patient population that could benefit from fitusiran, its expectations regarding its STAr pipeline growth strategy, and its plans regarding 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 may differ materially from those indicated by these forward-looking statements as a result of various important 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 drug 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, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage operating expenses, Alnylam's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation to update any forward-looking statements.
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