May 10, 2010 is a date that will forever loom large in the memories of employees left at Avexa. It was the day when the Australian group finally threw in the towel and announced that it would no longer be developing its lead product, HIV drug apricitabine (ACT), a nucleoside reverse transcriptase inhibitor (NRTI).
Avexa’s difficulties might also be an unpleasant and salutary warning of things to come for other smaller biotechnology companies trying to find partners for their NRTI-based drugs. The disease is increasingly well managed by existing older NRTIs, and there has been an advent of newer drugs in the market including Truvada and Atripla with even better efficacy and safety.
An analysis by EP Vantage of the current NRTIs in development shows that of the seven in clinical trials only one currently has a partner (see table below). The others are either still actively seeking one as in the case of Oncolys’ festinavir or have spent years being bounced backwards and forwards between various owners before ending up back in the hands of originators, minus the international deals that would make them a success.
|NRTI drugs in development|
|Status||Product||Generic Name||Company||Patent Expiry|
|Phase III||Apricitabine (ATC)||apricitabine||Avexa||Jun 2018|
|Phase II||MIV-310||alovudine||Medivir||Mar 2019|
|Dexelvucitabine/DFC (Reverset)||dexelvucitabine||Pharmasset||Aug 2025|
|Amdoxovir||amdoxovir||RFS Pharma||Dec 2015|
Medivir’s MIV-310 with its chequered and restless history is a case in point. The drug was originally licensed by Boehringer Ingelheim in July 2003, but was returned in March 2005 after Boehringer decided there was no clinical justification for continuing trials. The drug was then licensed to Presido, but that relationship did not go the distance either with the company handing back rights a year later, enabling Medivir to out-license the product to Chinese company Beijing Mefuvir Medicinal, one of the largest condom makers in China.
Pharmasset’s dexelvucitabine/DFC (Reverset) also knows the pain of rejection. The drug, which was licensed to Incyte in 2003, was returned in 2006 after it showed high levels of hyperlipasemia, or elevated pancreatic enzymes, and is currently languishing in phase II.
From the glory of a licensing deal in 1996 with Gilead Sciences, amdoxovir, which was developed by Emory University and the University of Georgia Research Foundation, found itself literally back on the shelf in 2004. In 2008 the universities struck a more down scale manufacturing based deal with RFS Pharma.
Time and money
Outlining the difficulties of landing a deal after its final negotiating partner walked away earlier this month, Avexa highlighted the time and money that would have to be expended to get approval for apricitabine, especially in light of other similar successful drugs in the US. This is a problem facing all of the smaller drug developers and is probably the biggest reason behind their lack of success.
If it had managed to win approval apricitabine would have been up against the likes of Gilead’s Truvada and Viread, highly successful combination drugs that have changed the landscape of HIV treatment, keeping patients healthy for longer with fewer side effects than some of the older mono or duo therapy NRTIs.
Additionally, the rapidly approaching patent expiry of some of these older drugs, including GlaxoSmithKline's suite of treatments including Combivir, Trizivir and Epzicom could also have made it difficult for Avexa to carve out a niche in the space.
But it is not just NRTI drugs in the HIV space that are struggling in the face of newer drugs. Last year, Ardea BioSciences admitted it was finding it difficult to find a partner for its non-nucleoside reverse transcriptase inhibitor (NNRTI) drug, RDEA806 (Therapeutic focus - Certain HIV drugs could struggle to find partners, June 25, 2009). In March, Achillion Pharmaceuticals admitted that it was still waiting for a large partner to take its HIV drug elvucitabine into phase III trials and would be not proceed without one, despite having completed phase II trials back in 2008.
With no hope of a global partnership Avexa has decided that one way forward could be smaller regional licensing deals, but these are unlikely to provide any meaningful payback on the development costs the group has spent on the product. Shares have plunged to record lows, losing 81% of their value over the course of a month and currently sit at just 2 cents.
The gloomy prospects for Avexa have left it assessing its strategic options, including M&A, licensing or frankly anything else that might help. If the group’s difficulties in trying to secure a partner are anything to go by this could be the fate that awaits others in the NRTI space trying to find a deal.