Ardea Biosciences' admission that securing a deal for its NNRTI (non-nucleoside reverse transcriptase inhibitor) drug, RDEA806, has been more challenging than anticipated is perhaps understandable, when considering that the company is fairly late to the game with this class of HIV treatment (Ardea admits that finding partner for HIV project has been challenging, June 25, 2009).
Of the 13 NNRTIs in active development, 5 remain unpartnered, 4 of which belong to Ardea, according to pipeline data from EvaluatePharma. A second class with a similar profile is the HIV integrase inhibitors; only 3 of the 12 products under development have yet to be snapped up by a larger player (see table below). The companies involved might find their partnering efforts similarly frustrating.
Still, the fact that these unpartnered integrase inhibitors, a new class of antiretroviral, are all at pre-clincal stages or research projects, means the companies are not likely to be desperate for partners just yet. However, should they move into the clinic, this could become an issue.
|HIV Treatments - count and analysis of product portfolio|
|Phase||Pharma Class||Total Count||Unpartnered assets||% unpartnered|
|Total marketed products||36|
|R&D (phase III - research project)||HIV vaccine||21||15||71%|
|HIV integrase inhibitor||12||3||25%|
|HIV maturation inhibitor||6||6||100%|
|Anti-HIV gene therapy||5||4||80%|
|Total R&D products||150||116||77%|
|Suspended/Abandoned in R&D||NNRTI||17|
|HIV integrase inhibitor||10|
|CD4 attachment inhibitor||8|
|Total Suspended/Abandoned products||160|
The company’s involved are Avexa, BioAlliance and Ambrilia Biopharma. Inhibitex has a number of pre-clinical programmes, but recently suspended all work on the HIV area to focus on hepatitis C, a trend which Ardea noted at the Piper Jaffray conference this week.
The first integrase inhibitor to reach the market is likely to be Gilead Science’s elvitegravir, which it licensed from Japan Tobacco in 2005. The drug is being trialled as part of a new combination HIV treatment, and analysts are anticipating marketing approval next year and sales of $416m by 2014, although its real value will lie in a combination product also in development.
Ardea’s efforts with its NNRTIs might also have been frustrated by the high number of failures in the field. The table shows that NNRTIs are the graveyard of HIV research, and the products have never been as successful in sales terms as the NRTIs. Johnson & Johnson’s new NNRTI Intelence, launched last year, for example, is forecast to generate sales of $565m by 2014. This is not an insignificant product but clearly not as huge as NRTIs like Gilead’s Truvada, which is seen generating $3.5bn by 2014.
Clearly HIV vaccines, to treat and prevent HIV, are attracting a lot of R&D interest and big pharma is already present. Sanofi-Aventis is most advanced with a phase III candidate ALVAC-HIV and another in phase II. Other big pharma efforts, from Merck & Co, Novartis and Glaxo are only in phase I.
This means with the wealth of pipeline candidates up for grabs, if the field makes progress further deals could follow. It is interesting to note that Gilead Sciences, which dominates the HIV space, has not declared any work in the area.
Whilst NNRTIs and HIV integrase inhibitors appear to have already been picked over by big partners, the above table indicates that there is plenty of novel research going on. Clearly much of it will be early stage and high risk, but areas like HIV maturation inhibitors and gene therapy approaches could be areas to watch if clinical successes are achieved, considering the high percentage of unpartnered assets available.