More than two years after being sent away by the FDA to conduct further trials, Dyax believes it is finally ready to file DX-88 for marketing approval in the final quarter of this year as a treatment for the rare genetic disorder hereditary angiodema (HAE).
The extensive series of clinical trials under its belt, including positive data from a phase III study published yesterday, mean the company has a good chance of winning approval this time round. It also means Dyax could be the first to have a small molecule-based treatment for the disorder on the market in the US, which considering the niche patient population and competition on the horizon, should be a significant advantage.
HAE sufferers lack the C1-inhibitor protein, and the disorder is characterised by periods of sudden and painful inflammation in the face, throat or extremities, which in rare cases is fatal. Because of the significant unmet need for effective treatments, particularly in the US, there has been a flurry of R&D activity in the last few years, while several late-stage deals have been struck in the last month.
Shire bought Jerini in July for $509m for its drug, called Firazyr, which recently won approval in Europe but will probably need another trial in the US. Viropharma bought Lev Pharmaceuticals a few weeks later for $443m for Cinryze, a protein replacement therapy that is the only product going for approval as a prophylactic treatment, with a PDUFA date of October 14. CSL has a very similar product awaiting an FDA decision called Berinert P, but in the acute setting, with a PDUFA date of September 5. (See EP Vantage coverage: EP Vantage Interview - Shire enters HAE market with Jerini buy, July 03, 2008 and ViroPharma takes gamble with Lev acquisition, July 16, 2008)
If DX-88 gets a priority review, which is likely considering it has orphan drug and fast track designation, a launch in the second half of 2009 is possible.
Despite potentially being several months behind CSL in the US, with whom it will compete in the acute setting, the convenience factor will be a big plus for DX-88. It is subcutaneously delivered, rather than administered via transfusion.
The CSL product is derived from donated blood plasma, and is essentially replacing the protein that HAE patients lack. Clinical trials and use in Europe for over 30 years has demonstrated a benign side effect profile, aside from the usual issues arising from transfusion, so this could be an advantage over DX-88, which has been associated with anaphylaxis.
Still, only two cases have been reported throughout all the trials, and although the FDA is likely to look closely at this issue, commentators believe it still should win approval. What it could mean, however, is that the FDA will be reluctant to approve the drug for home use, at least until the drug has been available for some time.
Self administration is the Holy Grail for HAE patients, who suffer from random and sometimes very frequent attacks; some people have up to 12 a month, and hospitalisation is currently required to receive treatment.
The biggest competitive threat on the horizon for Dyax is Shire and Jerini’s Firazyr, which is also subcutaneously administered. Realistically, however, approval in the US is not likely for at least another 12 months, probably longer, so Dyax, which is going it alone in the US, should have a fair amount of time to capture market share.
In Europe, the situation is reversed, with Firazyr ready to launch and DX-88, tentatively partnered with Dompe in the region, not yet filed.
The market potential for any of the HAE treatments is hard to gauge, not least because although around 10,000 patients in the US and Europe have been identified, the condition is thought to be very under-diagnosed. How the market develops in terms of preference for prophylactic over acute treatments is little more than guesswork at the moment and none of the players has revealed a pricing strategy.
First to market will of course be a huge advantage, and for Firazyr and DX-88, the first to win approval for self-administration will be important.
Consensus data from EvaluatePharma reveals that analysts have pencilled in sales of $277m for both DX-88 and Firazyr in 2014, and $280m for Cinryze. Data for Berinert is not available. However, once the acquisitions of Jerini and Lev go through and coverage by new analysts commence, those figures are likely to change.
Plus, with passage through the FDA to date far from plain sailing, both DX-88 and Firazyr were turned down on first attempt, the time lines for approval for any of the products is far from set in stone. Until drugs are launched and marketing underway, the final shape and size of the HAE market is very hard to picture.