PhIII data dents GSK's hopes for cancer vaccine

Coming into 2013 GlaxoSmithKline ($GSK) highlighted a cancer vaccine as one of its brightest late-phase candidates. Yet, like many cancer vaccines before it, MAGE-A3 has disappointed at the final hurdle.

The vaccine missed its first co-primary endpoint after failing to outperform a placebo in a Phase III trial of 1,345 melanoma patients. GSK gave patients in the treatment arm of the trial a dose of MAGE-A3, a protein found in 65% of advanced melanoma cases. The expectation was that the immune system would recognize the protein as foreign and attack it throughout the body, including in tumor cells. Data from the Phase III trial has undermined this theory, though, and strengthened the skepticism of industry analysts. 

"This asset was widely regarded as a 'wild card' by the market. While there had been some hope that this approach might work, the result is not a surprise," Alistair Campbell of Berenberg Bank wrote in a research note seen by Reuters. Some analysts tipped the vaccine to generate sales of more than $400 million a year by 2018, but Citigroup's Andrew Baum expects his peers to lower expectations now. Baum forecasts sales of $233 million in 2018.

Sales projections combine the potential of MAGE-A3 as a treatment for melanoma and lung cancer. GSK expects to report the first data from a Phase III trial in non-small cell lung cancer next year. While working to deliver the lung cancer data, GSK will continue its melanoma trial to assess if the vaccine is more effective in patients with a particular genetic profile. More immunologically responsive patients could benefit from the vaccine despite its failure in the broader population.

"That will be very important data we'll all be interested in. Let's say this vaccine doesn't work in all MAGE-A3 [patients], but what if it works in 50%? That would still be good," University of Texas MD Anderson Cancer Center surgeon Dr. Elizabeth Mittendorf told The Wall Street Journal. Data on this second co-primary endpoint is expected in 2015. Positive results in a subpopulation would be a big boost for Agenus ($AGEN), the biotech that makes the adjuvant used in MAGE-A3. Shares in Agenus closed down 23% after GSK said it missed its first co-primary endpoint.

- read Reuters' article
- check out the WSJ's piece (sub. req.)
- here's FierceBiotech's take