Eisai Revenues Set to Fall Off the 'Patent Cliff' as Sepsis Drug Hits Delay

by: EP Vantage

Bigger is definitely not better for Eisai’s share price

With patent expiry of its lead drug galloping towards it at high speed, the last thing that Eisai (OTCPK:ESALY) needed was a delay to one of the drugs it had picked as a cornerstone product to help it get over generic competition to Alzheimer’s treatment, Aricept, in November.

Thursday, the Japanese group announced that its phase III trial for severe sepsis with E5564 (eritoran) would continue to enroll patients to an agreed 2,000 patients. But the company had hoped that a trial involving just 1,500 patients might be enough the squeeze an NDA filing by June. Instead, with an extra 500 patients to find, it is now expected that a filing will have to take place next March, meaning the drug will not be on the market until early 2012. Shares in Eisai fell by 2% on the news.

Pressing need

Eritoran, and the other drugs the group is trying to push through its late-stage pipeline, is important because once Aricept loses patent protection this year, revenues are set to fall off the proverbial patent cliff at Eisai. Last year, the Alzheimer’s drug accounted for almost 40% of sales and an estimated 60% of profits - a big hole to fill.

The sepsis drug was also set to be the biggest growth driver at Eisai over the next six years and is the group’s third most valuable drug, worth $1.26bn according to EvaluatePhama's NPV Analyzer. While sales are currently forecast to hit $330m by 2014, given the nature of sepsis the company was predicting that the drug could eventually hit blockbuster status.

But, as well as providing yet another setback to Eisai’s plans to try to offset the patent loss of Aricept, the delay to filing of eritoran will be a blow to those trying to find an effective treatment for sepsis.

Limited options

The bacterial infection, which causes the body’s immune system to turn on itself and attack major organs, is thought to affect about 750,000 people in the US alone and has a mortality rate of between 30-35%, meaning roughly 250,000 people in the US die from the infection every year.

At present there is only one marketed product aimed at sepsis, Eli Lilly’s (NYSE:LLY) Xigris. But the drug is deeply flawed and its severe side effect profile, which includes bleeding incidents, coupled with its high cost and relatively small benefit in terms of lowering the risk of death, often means that it is only used as a last resort.

A recent analysis by EP Vantage also shows that there is very little in the development pipeline for this infection, with eritoran being the most advanced drug (Therapeutic focus - AstraZeneca makes rare advance with sepsis treatment, July 30, 2009). But with its trial now extended the drug could see competition appearing from both CytoFab, the drug that was in-licensed from Protherics (PTIL) by AstraZeneca (NYSE:AZN), and Agennix’s talactoferrin, which back in February produced some very positive longer term severe sepsis survival data.

Outside of these drugs there is little other than pre-clinical products, and the long list of drugs that have been abandoned in clinical trials shows just how difficult it is to find and develop effective treatments for the infection.

New way forward

Eisai’s approach to the disorder is a relatively novel one. Eritoran aims to block the activation of toll-like receptor 4 (TLR4), which is part of the immune system and when activated is thought to contribute to the cascade that causes severe sepsis.

But one of the key abandoned products for sepsis in recent times was Takeda’s (OTCPK:TKPHF) TAK-242, another TLR4 over which the group decided to terminate phase III development in February 2009.

Phase II results from eritoran have also been mixed; in December Eisai reported the results of a 300-patient study using a low and high dose of the drug against placebo. The 28-day mortality rate in the placebo group was 33.3%, 32% in the low dose group and 26.6% in the high dose group. Unfortunately for Eisai, while the high dose group reduced mortality by 6.7 percentage points, this was not statistically significant.

Mixed data

The trial also found that the greatest benefit was observed in patients at the highest risk of mortality, where using the highest dose of the drug resulted in a mortality rate of 33.3% compared with 56.3% in the placebo group.

While this was again not statistically significant, it has formed the basis of the now 2,000 patient Access trial and Eisai will be hoping that the now much larger trial will show better benefits than the phase II trial. But as previously stated, because of the nature of sepsis, with so few treatment options, even a relatively minimal benefit might still be acceptable to regulators.

So while eritoran may be arriving slightly later to the party and its present might not be the best one on the table, with so few other guests expected any time soon, if the drug has a better safety profile than Xigris it still might be a big success, one that Eisai will welcome to help offset the loss of Aricept.