A drug failing in Phase III trials has an impact beyond the company developing it.
The latest example is Celldex's Rintega brain-tumor vaccine. The company stopped its final-stage study on Monday due to poor results. The news didn't just cause Celldex shares to collapse 53.72 percent. It also means years of research may go up in smoke, patients will be left without a better treatment option, and an entire approach to fighting cancer looks shakier than ever.
The setback is devastating, but likely not fatal news for Celldex; the New Jersey biotech has a strong research pedigree and other promising (non-vaccine) medicines in the pipeline. But the same can’t be said for cancer vaccines, which were already nearly on drug development death watch.
The hope for a therapeutic cancer vaccine is more than a century old. There have been a variety of different approaches, with some tantalizing results, but no real successes.
Dendreon's Provenge is the only such drug to make it to market in the U.S. Approved by the FDA in 2010, it sold so poorly compared to expectations that Dendreon was driven to file for bankruptcy in 2014. The company's assets met a fate that may be, depending on your point of view, worse than death: acquisition by Valeant. Dendreon's vaccine was an unappealing mix of high price, high manufacturing cost and only modest benefit. At its height in 2010, amid blockbuster expectations for Provenge, Dendreon was worth more than $7 billion. Valeant acquired its assets for $495 million in early 2015.
Many other programs have managed to progress into late development stages, but no further. GlaxoSmithKline spent big to take a MAGE-A3 cancer vaccine to Phase III trials, only for it to fail in both lung cancer and melanoma in 2013 and 2014. Germany's Merck KGaA also invested heavily in a vaccine program that has failed to deliver. A variety of small companies including Cell Genesys, Genitope, and Favrille have puttered out chasing the approach. Some of these companies had been working on vaccines since the 1990s; research on the approaches some of them used went back decades before that.
If you were going to bet on another cancer vaccine, Celldex's might have been it, given the company's pedigree. It was spun off from Medarex, a biotech purchased by Bristol-Myers Squibb for $2.4 billion in 2008. That deal netted Bristol-Myers Squibb Opdivo, a blockbuster cancer immunotherapy drug expected by analysts to do $9.7 billion in sales by 2020.
Rintega produced encouraging results in earlier trials. And it was performing about as well in the late-phase trial, with a median survival time of 20.4 months for patients who took the drug. But the placebo control group that didn't take the drug had a median survival time of 21.1 months, far longer than is usual with this disease. That requires a close look at the data. The result doesn't necessarily spell the end of the vaccine, but it's not encouraging.
There are still plenty of companies chasing vaccines, including Bavarian Nordic and Inovio. New ventures such as Gritstone Oncology, Caperna, and Neon Therapeutics are trying new approaches to vaccines that could conceivably work better, by more successfully targeting individual patients and tumors. And there's been some noise about salvaging vaccines by combining them with other immunotherapy drugs.
But there's a long legacy of disappointment here that's hard to discount, especially for companies still chasing approaches that have failed. It might be time for investors and companies to move on. Vaccines have already been eclipsed by other therapies that seem to more successfully harness the immune system, including checkpoint inhibitors such as Opdivo and cell therapies such as CAR T.
Celldex still has options. This was a major program for the company, its latest-stage drug, and the result is a shocking setback. But it has an interesting pipeline that's not vaccine-focused, including a breast-cancer drug in a late-stage trial and a drug in combination trials with other immune therapies in multiple cancers. And it has $289 million in cash and equivalents, enough to get it through 2017, at least.
The company can do some soul-searching and move on. But vaccine-only companies are stuck on a path that looks increasingly like a dead end.
This column does not necessarily reflect the opinion of Bloomberg LP and its owners.
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