Flu antivirals in demand but few options in pipeline

The discovery that the dominant strains of flu circulating in the US this year are resistant to Roche’s Tamiflu has prompted many medical experts to call for more antiviral drugs to treat sufferers.

With only Tamiflu and GlaxoSmithKline’s Relenza on the market, other than much older medicines which are now largely redundant, options are clearly limited. Unfortunately, it appears that the R&D pipeline is also narrow, with only three products in clinical stage development, according to EvaluatePharma (see table below).

The most advanced product is CS-8958, jointly owned by Daiichi Sankyo and Biota, the Australian biotech which discovered Relenza. Like Relenza and Tamiflu, the drug is a neuraminidase inhibitor, but a long-acting version, therefore seen as a next-generation product.

Daiichi Sankyo has started phase III trials in Asia, whilst analysts anticipate a partner will be brought on board to fund pivotal trials in the US and Europe. It is hoped that the long-acting version will be more potent and effective than the two existing treatments, making it particularly appealing for use in the pandemic stockpiling market.

Biota also has a range of pre-clinical compounds called Flunet which the company said could be considered third-generation anti-influenza products. Their development is being funded by an $8.5m grant from the US National Institute of Health.

Earlier stage

In phase II development is peramivir from BioCryst Pharmaceuticals, another neuraminidase inhibitor. The drug has a chequered history, it was originally developed in oral form under a deal with Johnson & Johnson and made it into phase III, although rights were returned to the BioCryst in 2001 before the study completed. BioCryst completed the trial, which failed to meet its primary endpoint, and development of the oral form was scrapped. The resurgence of concerns about a flu pandemic prompted the company to dust off research into this new intravenous formulation a few years ago.

Still, progress has been slow, despite a $100m, four-year grant from the US Department of Health and Human Services to develop the drug. Japanese partner Shionogi was supposed to have started phase III trials in Japan by now, but news has not been forthcoming, and the path forward for the drug is unclear.

Lastly, an anti-viral called T-705 is in phase II development by Japanese group Toyama Chemical, although updates have not been given by the company since it started a phase I in the US in March 2007. The drug is a viral RNA polymerase inhibitor, acting on viral genetic copying to prevent reproduction, and would offer an alternative to the neuraminidase inhibitors.

Resistance?

Opinion is divided over whether resistance is building among the flu strains to Tamiflu, or whether the drug’s ineffectiveness is down to a random genetic mutation. Whilst resistance issues have not been noted with Relenza, if the virus is able to overcome Tamiflu, it is probably only a matter of time before it too faces the same issues.

With the majority of research into antivirals focusing on neuraminidase inhibitors, scientists’ calls for greater options may not be realised for some time.

Influenza antivirals under development
  Product Pharmacological Class Company
Phase III CS-8958 Neuraminidase inhibitor Daiichi Sankyo/Biota
       
Phase II Peramivir Neuraminidase inhibitor BioCryst Pharmaceuticals/Shionogi
  T-705 Anti-viral Toyama Chemical
       
Phase I Influenza Product * Anti-viral OptiNose
       
Pre-clinical Anti-Influenza Monoclonal Antibody Anti-influenza MAb Kyowa Hakko Kirin
  Flunet Neuraminidase inhibitor Daiichi Sankyo/Biota
  Peramivir-CDT Neuraminidase inhibitor BioCryst Pharmaceuticals/SCOLR Pharma
  Influenza RNAi Therapeutic (G00101)  Influenza RNAi therapeutic  MDRNA
  AVI-6001 Influenza antisense AVI BioPharma
  Avian Influenza collaboration Anti-influenza MAb OMRIX Biopharmaceuticals
  Seasonal Influenza Anti-influenza MAb OMRIX Biopharmaceuticals
  MIMP T cell regulator IRX Therapeutics
       
Research project  ALN-FLU01 Influenza RNAi therapeutic Novartis/Alnylam Pharmaceuticals

*Very little information is available about this product

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