GlaxoSmithKline's cancer vaccine MAGE-A3 suffers its second PhIII flop

GlaxoSmithKline's once high-flying hopes in the cancer vaccine MAGE-A3 have crashed to earth--for a second time. Once a top Phase III program at the pharma giant, MAGE-A3 failed to hit a pair of primary endpoints for non-small cell lung cancer, its second failure since the melanoma flop that occurred in the first hurdle of the study reported last fall.

The study marches on as scheduled, though, as investigators search for a possible subpopulation of cancer patients who might benefit from the therapy.

The late-stage stumble for Glaxo ($GSK) shaved close to 2% off its stock price Thursday morning, an indication of the market potential that this program once held. And it's bad news for Lexington, MA-based Agenus ($AGEN) as well, which provided the adjuvant used for the cancer vaccine. Agenus's shares were hammered last fall when GSK's first Phase III for MAGE-A3 failed for melanoma. This morning the stock was down 13% in trading ahead of the open.

This second consecutive failure for MAGE-A3 highlights a key concern for GlaxoSmithKline. The R&D division, which underwent a major reorganization in 2008, has enjoyed a string of significant new drug approvals. But even GSK R&D chief Moncef Slaoui noted that these new drugs coming along weren't the kind of really innovative, potentially high-reward therapies that excited him. He was more eager to explore cutting-edge therapies like the heart drug darapladib--gained from the acquisition of Human Genome Sciences--and MAGE-A3. And darapladib failed its first Phase III last fall. Another top prospect for the Duchenne muscular dystrophy therapy drisapersen is being handed back to Prosensa ($RNA) after that drug failed a late-stage program as well last year.

The failure also marks a setback for the cancer vaccine field. While immuno-oncology therapies like MK-3475 and nivolumab have captured analysts' attention, the vaccines have floundered in a string of late-stage failures. MAGE-A3 was designed to spur an immune system attack on antigen 3, a protein found on the surface of cancerous cells. Merck KGaA had failed in its own late-stage effort with the cancer vaccine Stimuvax, now renamed tecemotide, but recently said it would take a second swipe at a pivotal study after finding a specific population of patients that appeared to benefit from it.

The search for subpopulations will continue into 2015 at GSK, but don't expect to see much excitement at the company for its prospects. Among all the Big Pharmas, GSK has been one of the quickest to publicly acknowledge failure when it happens and move on to other efforts.

"We are disappointed that the trial did not demonstrate a benefit for overall MAGE-A3 positive patient population, but we remain committed to the effort to identify a sub-population of NSCLC patients who may benefit from this investigational treatment," said Vincent Brichard, the head of immunotherapeutics at GSK Vaccines.

- here's the release