Reward appeared to win out over risk yesterday after the FDA’s Cardiovascular and Renal Drugs Advisory Committee unanimously recommended approval for Daiichi Sankyo and  Eli Lilly’s anti-clotting drug prasugrel. 

The vote, that saw all nine members of the committee give the drug the thumbs up, is a massive positive for the drug that has faced a series of delays to approval. Given the well documented safety issues a final pass from the FDA, which has increasingly shown a willingness to take decisions that are at odds with that of its advisory committees, now appears likely, but cannot be guaranteed.

Investors also appeared less than certain of the regulatory chances of the drug, which is now known as Effient in the US and Efient in Europe. Shares in  Daiichi Sankyo closed ¥25 lower in Tokyo at ¥1,953, and while  Lilly shares closed 4% higher at $38.69 yesterday ahead of the announcement, which came after the stock markets had closed, they were only up 29 cents in early US trading today. 

Waiting game

Effient is important to both groups. With sales forecast to reach $1.42bn by 2014, it is the biggest growth driver at  Eli Lilly over the next seven years and  Daiichi’s second most valuable drug, worth $1.7bn according to EvaluatePharma’s NPV Analyzer

It also represents one of Lilly’s best chances to, if not quite fill the gap left by the patent expiries of its two biggest products Zyprexa and  Gemzar, but make it a lot smaller. 

When the drug will finally hit the shelves in the US remains uncertain, as the FDA has yet to set a new PDUFA date. But the fact that last February it received a priority review; missed a September PDUFA date; and now has a ruling from the advisory committee, should provide some impetus to get a date in the diary.

In December, European regulators recommended approval of the drug, including a lower 5mg dose, which could be used in the three risk groups. If approved by the European Commission, the drug could be on sale by the end of the first quarter. 

Clear value

What is in Effient’s favour for US approval is its efficacy; compared with current gold standard treatment Plavix, it notches up an impressive 19% reduction in cardiovascular death, heart attack or stroke, as well as a 52% reduction in stent thrombosis. 

The increased risk of bleeding in certain sets of patients is well known and label warnings prohibiting its use in those who weigh less than 60kg, or are older than 75, or who have previously had a stroke, are expected. Panel members also appear to have discounted the higher incidence of cancer among patients taking Effient against placebo as a statistical blip rather than a serious concern, and have recommended that it not be part of a black box warning.  

So while omens look largely favourable for US approval, the restrictions on use of the 10mg formulation mean that it will not be the challenger to Plavix that some thought it might become. Instead, the drug is more likely to carve out a very big niche, in the artery clearing and stent implant market.  

Some analysts believe that it could achieve about a fifth of the revenues of the Bristol Myers-Squibb and Sanofi-Aventis drug, which is forecast to have 2008 sales of $9.34bn. Interestingly,  Lilly and  Daiichi have also submitted the 5mg dose of the drug for US approval, while many think its chances of endorsement are slim, if recommended then Effient's sales could rise given that it could also be used in the at-risk populations.

Bigger slice of the pie

However, both doses of the drug could in the future benefit from market share increases, given that studies are starting to show that a large number of patients taking Plavix in combination with heartburn pills, or those who lack the metabolising enzyme CYP2C19, receive no benefit from the drug. The number of non-responders is thought to be anywhere between 15%-30%, and there have been reports of higher mortality in patients without the CYP2C19 enzyme. So despite the risks associated with  Effient, doctors may welcome an alternative to Plavix. 

As such, with so much to play for, Daiichi and  Lilly will be hoping that their long and painful journey to approval will soon be coming to a successful end.