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 (MRK 3.27%), 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.