Acute care biopharmaceutical company Cubist Pharmaceuticals and RNAi therapeutics firm Alnylam Pharmaceuticals have decided to collaborate to develop and commercialise Alnylam's ALN-RSV programme.

This RSV-specific RNAi therapeutic programme includes ALN-RSV01, which is currently in Phase II clinical development for the treatment of respiratory syncytial virus (RSV) infection in adult lung transplant patients, as well as several other potent and specific second-generation RNAi-based RSV inhibitors in pre-clinical studies.

The collaboration is structured as a 50/50 co-development and profit share arrangement in North America, and a milestone- and royalty-bearing license arrangement in the rest of the world outside of Asia, where Alnylam and Kyowa Hakko Kirin Co are working on ALN-RSV.

Alnylam will receive an upfront payment of $20 million and, in addition, is eligible to receive development and sales milestone payments from Cubist that could total $82.5 million, for a total in upfront and potential milestone payments of $102.5 million, as well as double-digit royalties on net sales outside of North America and Asia.

After achieving certain development milestones, Alnylam could convert the North American co-development and profit share to a royalty-bearing license with development and sales milestones. Cubist will have sole rights for commercialization of the ALN-RSV program worldwide outside of Asia, subject to the cost and profit sharing in North America.

Michael W. Bonney, president and CEO of Cubist. "We expect that this collaboration will leverage the development expertise and commercial success we have achieved in the area of infectious disease. There is significant need for novel therapeutics to effectively treat patients with RSV infection, a leading cause of paediatric hospitalisation and a prevalent infection in certain adult populations."

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 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.

"Partnering this programme brings additional critical mass to the advancement of ALN-RSV01 and/or second-generation RSV-specific RNAi therapeutics in our broader programme, which we aim to advance through ongoing pre-clinical studies toward potential clinical studies as early as 2010," says John Maraganore, Ph.D., Alnylam's CEO. "The partnership also provides Alnylam with yet additional financial flexibility to invest beyond RSV in the multiple product opportunities represented by our growing pipeline of novel RNAi therapeutics."

In 2008, Alnylam conducted the GEMINI study in which ALN-RSV01 was evaluated in a double-blind, randomised, placebo-controlled Phase II clinical trial. Data from this study showed that intranasally administered ALN-RSV01 demonstrated statistically significant anti-viral efficacy with an approximately 40 per cent relative reduction in RSV infection rate and a 95 per cent increase in the number of infection-free subjects, as compared with placebo.

The RNAi therapeutic is currently being studied in a double-blind, randomized, placebo-controlled Phase II clinical trial to assess the safety and tolerability of aerosolised ALN-RSV01 in adult lung transplant patients naturally infected with RSV.

As a secondary objective, this trial will evaluate the anti-viral activity of ALN-RSV01 in patients with a naturally acquired RSV lower respiratory tract infection. Based on these and other data, Cubist and Alnylam will aim to maximize the value of the entire RSV program for advancement in pediatric and adult RSV-infected patients.

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 hospitalisation 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 hospitalisations 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.

Alnylam is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington's disease, and TTR amyloidosis. The company  has major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko, and Cubist and is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and commercialisation of microRNA therapeutics.