It has been a long and at times bruising battle for Eli Lilly (LLY) and Daiichi Sankyo (OTC:DSKYY) to get US approval for their anti-blood clot drug, Effient, but on Friday, 19 months after first filing, the groups got the rubber stamp from the FDA, an event that had been expected following a positive recommendation from an advisory committee earlier in the year (FDA panel removes another hurdle for Effient approval , February 4, 2009).
However, last week’s almost certain celebrations would have been tempered by the fact that the FDA has imposed its strictest caution on the drug, slapping it with a black box warning over severe and sometimes fatal bleeding. Analysts were quick to deduce that the restriction on use, which in effect only gives it approval in the very narrow indication of preventing blood clots from forming and causing a heart attack or stroke during or after angioplasty surgery, would impact uptake of the product.
There had already been worries that Effient, which was approved in Europe in April and called Efient, would have limited use once it was approved, taking some of the gloss from its previously expected blockbuster status. Since March 2007, 2012 sales forecasts for the drug have almost halved from $1.55bn to $874m last month, according to consensus forecasts from EvaluatePharma, as concerns mounted.
Forecasts may now come down even further, but perhaps some perspective is needed. The drug’s effectiveness over current gold standard Plavix - it reduces the number of non-fatal heart attacks - may mean that sales do not reach the lofty heights analysts previously over-enthusiastically forecast, its usefulness as an alternative treatment in surgeons’ armoury should still mean sales of, or just over, $1bn by 2014.
Effient could also see more sales come its way due to the growing concern and awareness that Plavix is ineffective in patients taking some heartburn pills, or those without the CYP2C19 enzyme, where there have also been concerns over higher mortality rates among Plavix users.
Daiichi and Lilly are sensibly looking at genetic differences in efficacy for Plavix, whose non-responders are thought to range from anywhere between 5%-30%, in a large ongoing study comparing Effient with Plavix. Finding a bio-marker for patients who derive no benefit from Plavix would be an enormous boon for Effient.
What the market also appears to have overlooked is that both doses of Effient have been approved. While the majority of test data has occurred with the 10mg dose, the FDA has also given the green light to the 5mg dose, which might avoid some of the more severe side effects of the higher dose and persuade doctors to switch treatments to benefit from Effient’s improved efficacy.
Wider spread use of the 5mg version, Effient’s increased effectiveness and, if proven, the genetic argument for switching from Plavix could all help Effient continue to gain market share even when Plavix, which is already under generic attack in Europe, loses patent protection in the US in 2011 and cheap generics flood the market.
While the market may still be worrying about the drug’s potential, for both Lilly and Daiichi approval will come as a blessed relief. The numbers may have been scaled back, but the product remains a significant growth driver for both companies over the next six years.
The additional revenue will help Lilly, which is struggling with the very real worry that between now and the end of 2011 four of its drugs, which last year had combined sales of $6.2bn, will lose patent protection, including Zyprexa and Gemzar. Other big sellers such as Cymbalta and Humalog will have fallen by 2013.
For Daiichi, as well as upping the recent sparse number of approvals, the group will now at least have some good news to show investors, who have been badly stung by the group’s purchase of a majority stake in Indian generic group, Ranbaxy Laboratories (OTC:RBXLF), in June 2008.
This May, the group reported its biggest ever full-year loss after it was forced to spend $3.45bn writing down its stake after Ranbaxy suffered an export ban and investigation by the FDA over falsifying drug production data.
But it is not just Lilly and Daiichi that will be happy, AstraZeneca (AZN) can also take some cheer from the approval. Although the group is some way behind in launching its phase III anti-clotting drug, Brilinta, which like Plavix and Effient is also an ADPR antagonist, it recently reported positive top line data. If it manages to show similar efficacy with none of Effient’s bleeding problems, when the full data is presented this summer, it rather than Effient could be the real beneficiary in the anti-clotting market.