Alnylam Achieves First Human Proof of Concept for an RNAi Therapeutic with GEMINI Study
"With the positive results from GEMINI, we believe that Alnylam has demonstrated the first ever human proof of concept with an RNAi therapeutic," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "As such, these new data represent a key milestone and a major 'de-risking' event for the advancement of RNAi therapeutics, as well as important progress for our RSV program. While there's more to do in our efforts, these results also highlight Alnylam's continued leadership in the field of RNAi therapeutics, and our commitment to advancing this promising new class of medicines to patients."
The goal of the GEMINI study was to establish the anti-viral activity, safety, and tolerability of ALN-RSV01 in an experimental RSV infection model. GEMINI was a double-blind, placebo-controlled study, where a total of 88 adult subjects experimentally infected with RSV was randomized to receive ALN-RSV01 or placebo. ALN-RSV01 or placebo was administered intranasally for five consecutive days -- two days prior and three days after viral inoculation. Efficacy measures included infection rate and the effects of treatment on viral dynamics and clinical symptoms. As designed, GEMINI had sufficient power to detect a statistically significant difference in infection rate between ALN-RSV01 and placebo.
Results from this trial showed that:
-- subjects receiving ALN-RSV01 experienced a 38.1% reduction in infection rate as measured by plaque assay (P less than 0.01);
-- similar reductions in infection rate were obtained with other measurements of viral infection, including RT-qPCR, spin-enhanced culture, and RSV antigen assay; the overall infection rate by any of these measures showed a statistically significant anti-viral effect for ALN-RSV01 (P less than 0.025);
-- treatment with ALN-RSV01 also resulted in nearly a doubling -- a 95% increase -- in the number of subjects who remained free of infection (P less than 0.01); 12 of 42 subjects receiving placebo were uninfected as compared with 24 of 43 subjects treated with ALN-RSV01;
-- measurements of viral dynamics showed consistent trends favoring an ALN-RSV01 treatment effect, including viral AUC (area under the curve), viral load, peak viral load, duration of viral shedding, and mean daily viral load;
-- in this relatively small study, there were no significant difference in clinical symptoms; and,
-- ALN-RSV01 was found to be safe and well tolerated.
"GEMINI was designed as a robust, randomized, placebo-controlled study and the results show that ALN-RSV01 demonstrates clear anti-viral activity," stated Akshay Vaishnaw, M.D., Ph.D., Vice President, Clinical Research at Alnylam. "We are very pleased with the outcome of the study which showed activity for an RNAi therapeutic across several measures, including the incidence of infection and viral dynamics. We believe these findings point to the potential for clinical benefit with ALN-RSV01 in a naturally infected patient population, and we look forward to initiating a Phase II study in naturally infected adult patients in the first half of this year."
"These promising new human data demonstrate significant anti-viral activity for an RNAi therapeutic in a major respiratory disease, an accomplishment that is notable in clinical medicine," said John P. DeVincenzo, M.D., Associate Professor of Pediatrics and Infectious Diseases at the University of Tennessee Health Science Center and Principal Investigator for the GEMINI study. "Moreover, with a positive outcome in GEMINI, ALN-RSV01 represents the first new approach in decades for a drug demonstrated to have human anti-viral efficacy against RSV. These data support continued development of the RNAi therapeutic for the treatment of RSV infection, a major unmet medical need."
Conference Call Information
Alnylam will host a conference call on Friday, February 29, 2008 at 8:30 a.m. ET to discuss the results of the Phase II GEMINI study. To access the call, dial 888-396-2384 (domestic) or 617-847-8711 (international) five minutes prior to the start time and provide the passcode 86570853. A replay of the call will be available from 10:30 a.m. ET on February 29, 2008 until March 7, 2008. To access the replay, dial 888-286-8010 (domestic) or 617-801-6888 (international), and provide the passcode 79263826.
A live audio webcast of the call will also be available on the "Investors" section of the company's website, www.alnylam.com. An archived webcast will be available on the Alnylam website approximately two hours after the event and will be archived for 14 days.
About Respiratory Syncytial Virus (RSV)
RSV is a highly contagious virus that causes infections in both the upper and lower respiratory tract. RSV infects nearly every child at least once by the age of two years and is a major cause of hospitalization due to respiratory infection in children and people with compromised immune systems, and others. RSV infection typically results in cold-like symptoms but can lead to more serious respiratory illnesses such as croup, pneumonia, bronchiolitis, and in extreme cases, death. RSV infection in the pediatric and adult populations account for more than 300,000 hospitalizations per year in the U.S. In addition, RSV infection in infants has been linked to the development of childhood asthma. As a result, there is a significant need for novel therapeutics to treat patients who become infected with RSV.
About RNA Interference (RNAi)
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. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (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.
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including hypercholesterolemia, liver cancers, and Huntington's disease. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, and Roche. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has established "RNAi 2010" which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, visit www.alnylam.com.
Alnylam Forward-Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation statements concerning the timing for the commencement of clinical trials and studies, the need for novel RSV therapeutics, its views with respect to the potential for RNAi therapeutics, including ALN-RSV01, its view of the meaning and significance of the data from the GEMINI study, and the company's plans for achievements by the end of 2010, 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 risks related to: Alnylam's approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's dependence on collaborators; and Alnylam's short operating history; as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. 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 does not assume any obligation to update any forward-looking statements.
Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Yates Public Relations
Kathryn Morris, 845-635-9828
Posted: February 2008