GlaxoSmithKline shutters lung cancer vaccine study on latest MAGE-A3 setback

Just days after announcing that investigators had red-flagged a high-profile Phase III study of the cancer vaccine MAGE-A3 after failing to hit two primary endpoints for non-small cell lung cancer, GlaxoSmithKline ($GSK) has decided to bring a last-stab effort to find a subpopulation of patients who could benefit from the therapy to a halt. GSK says it was not possible to find a genetically defined group of patients who responded.

With the lights being flipped off on their Magrit trial, the pharma giant has one last effort underway on MAGE-A3. Investigators are sorting through the subpopulation data from another late-stage trial on melanoma after failing on the first co-primary endpoint. That final endpoint is expected to read out in 2015, but analysts also note that melanoma represents only a small market compared to lung cancer.

The latest news about MAGE-A3 reduces Glaxo's initial bonfire of expectations in the cancer vaccine to a flicker as another one of Big Pharma's high-risk, high-reward drugs flames out in Phase III. GSK's heart drug darapladib was also in the group before failing the first of its Phase III trials. Glaxo put plenty of cash behind that treatment as well and wants to see results from another late-stage study now underway before making a final call on it.

Agenus ($AGEN), which provided the adjuvant on MAGE-A3, is still exposed to an investor backlash, though even before this point there may have been little if any expectation that the program would pay off.

This latest setback will highlight yet again the fading hopes in cancer vaccines that look to stimulate an immune response to fight the disease. While Merck ($MRK), Bristol-Myers ($BMY) and Roche ($RHHBY) have made some amazing progress with PD-1 and PD-L1 approaches in taking the brakes off the immune system, tapping on the accelerator with an adjuvant and adjusting the immune system to recognize and destroy cancer cells--in this case through the protein MAGE-A3--has generally led to relatively weak responses in patients. There are a number of experimental efforts underway still to prove that the approach can have a dramatic effect--including Merck KGaA's second stab at Stimuvax--but the field is operating under a cloud.

For GlaxoSmithKline, which is being left out of the immuno-oncology race dominated by rivals, the failure also highlights its struggle coming up with big new drugs that can generate multibillion dollar annual returns. The company has had a string of significant approvals in the past year, but is likely to face some stiff headwinds when it comes to capitalizing on them in the marketplace.

Vincent Brichard, GSK's head of immunotherapeutics, said in a statement that he was "extremely disappointed. … We hope that the data generated in this trial will advance our understanding of the science of immunotherapeutics, and ultimately towards development of new therapies."

- here's the release

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