Overall Survival Will Be Critical for Endocyte's Vintafolide

The CHMP decision recommending European approval is great news for Endocyte, but success in the U.S. will require meeting a more stringent standard for efficacy.

Mar 28, 2014 at 9:00AM

Shares of Endocyte (NASDAQ:ECYT) nearly doubled overnight when it announced positive results from a Phase IIb trial of vintafolide and docetaxel in non-small cell lung cancer (NSCLC). At the same time, the company reported that Europe's Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion on marketing authorization for the drug for ovarian cancer. Both pieces of news are indeed very promising for the drug.

Endocyte partnered with Merck in 2012 for development of vintafolide in a deal worth $120 million up front with potential milestone payments up to $880 million. Endocyte is entitled to an equal share of U.S. profits and royalties of 15 to 20 percent in other countries. Peak sales estimates, assuming clinical and regulatory success, are over $1 billion. But there are significant hurdles to achieving that success.

Digging into the numbers
In the lung cancer trial, risk of death was reduced by 25% for patients receiving a combination of vintafolide and docetaxel compared to docetaxel alone. Additionally, the CHMP's opinion is obviously a good sign for chances of European approval. However, the lack of evidence for efficacy based on overall survival could be an obstacle to FDA approval in either indication.

In NSCLC, Endocyte tested the drug alone and in combination with docetaxel, with a group receiving docetaxel alone for comparison. The trial met the predefined threshold for statistical significance of achieving a p-value of less than 0.10 for its progression-free survival (PFS) endpoint. However, the company did not break down the numbers for survival or report on secondary endpoints (including overall survival), saying that it would present those results at an upcoming medical conference.

PFS is understood as the interval between treatment and further progression of disease. It is often used as a surrogate endpoint in cancer studies, replacing the lengthier wait time for overall survival. The FDA, however, has taken a firm stand against PFS for approval purposes, requesting the "gold standard" of overall survival data instead.

Endocyte reported that its early data for overall survival showed "trends" toward benefit in the group receiving a combination of vintafolide and docetaxel. That means that the calculations showed a benefit, but that it does not meet statistical significance. Since the trial is ongoing, the company expects and hopes that the combination group will achieve a statistically significant benefit by the time it's done.

The single agent trial arms for vintafolide alone and docetaxel alone have achieved median overall survival. The combination arm has not yet reached that point, however, which is good news. It means that not enough patients in that group have died to calculate an overall survival benefit.

For U.S. approval purposes, overall survival results are crucial. Although progression-free survival is a positive indicator in that direction, as are trends in the study toward significance, at this point it could go either way.

The ovarian cancer indication
Progression-free survival is also the basis of the application package for vintafolide in ovarian cancer in Europe. That program, carried out in collaboration with Merck (NYSE:MRK), is also supported by clinical trial results based on progression-free survival. The Phase II PRECEDENT trial gave a result of 5.0 months of progression-free survival for patients with platinum-resistant ovarian cancer treated with vintafolide plus pegylated liposomal doxorubicin (PLD). This is compared to 2.7 months for those treated with PLD alone.

An investigational imaging agent, etarfolatide, was used to identify a group of patients with folate receptor-positive tumors, and in that group the difference in PFS was 5.5 months for patients receiving vintafolide plus PLD compared to 1.5 months for PLD alone.

Endocyte and Merck are running a Phase III trial of vintafolide and etarfolatide in platinum-resistant ovarian cancer to confirm its Phase II results as they await European approval.

Foolish conclusion
The positive CHMP opinion in ovarian cancer is great news for Endocyte. Until the company can show some statistically significant overall survival results in either ovarian cancer or NSCLC, however, its potential to get the drug approved in the U.S. will be in question. That will in turn weigh down the company's stock value. Likewise, if and when it hands in those OS results, it will mean a great deal for potential success of the drug.

3 stocks that could become your next huge winner
The one sure way to get wealthy is to invest in a groundbreaking company that goes on to dominate a multibillion-dollar industry. Our analysts have done it before with other great biotech stocks. And now they think they've done it again with three stock picks that they believe could generate the same type of phenomenal returns. They've revealed these picks in a new free report that you can download instantly by clicking here now.

Catherine Shaffer has no position in any stocks mentioned. The Motley Fool has no position in any of the stocks mentioned. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.

Money to your ears - A great FREE investing resource for you

The best way to get your regular dose of market and money insights is our suite of free podcasts ... what we like to think of as “binge-worthy finance.”

Feb 1, 2016 at 5:03PM

Whether we're in the midst of earnings season or riding out the market's lulls, you want to know the best strategies for your money.

And you'll want to go beyond the hype of screaming TV personalities, fear-mongering ads, and "analysis" from people who might have your email address ... but no track record of success.

In short, you want a voice of reason you can count on.

A 2015 Business Insider article titled, "11 websites to bookmark if you want to get rich," rated The Motley Fool as the #1 place online to get smarter about investing.

And one of the easiest, most enjoyable, most valuable ways to get your regular dose of market and money insights is our suite of free podcasts ... what we like to think of as "binge-worthy finance."

Whether you make it part of your daily commute or you save up and listen to a handful of episodes for your 50-mile bike rides or long soaks in a bubble bath (or both!), the podcasts make sense of your money.

And unlike so many who want to make the subjects of personal finance and investing complicated and scary, our podcasts are clear, insightful, and (yes, it's true) fun.

Our free suite of podcasts

Motley Fool Money features a team of our analysts discussing the week's top business and investing stories, interviews, and an inside look at the stocks on our radar. The show is also heard weekly on dozens of radio stations across the country.

The hosts of Motley Fool Answers challenge the conventional wisdom on life's biggest financial issues to reveal what you really need to know to make smart money moves.

David Gardner, co-founder of The Motley Fool, is among the most respected and trusted sources on investing. And he's the host of Rule Breaker Investing, in which he shares his insights into today's most innovative and disruptive companies ... and how to profit from them.

Market Foolery is our daily look at stocks in the news, as well as the top business and investing stories.

And Industry Focus offers a deeper dive into a specific industry and the stories making headlines. Healthcare, technology, energy, consumer goods, and other industries take turns in the spotlight.

They're all informative, entertaining, and eminently listenable. Rule Breaker Investing and Answers are timeless, so it's worth going back to and listening from the very start; the other three are focused more on today's events, so listen to the most recent first.

All are available for free at www.fool.com/podcasts.

If you're looking for a friendly voice ... with great advice on how to make the most of your money ... from a business with a lengthy track record of success ... in clear, compelling language ... I encourage you to give a listen to our free podcasts.

Head to www.fool.com/podcasts, give them a spin, and you can subscribe there (at iTunes, Stitcher, or our other partners) if you want to receive them regularly.

It's money to your ears.


Compare Brokers