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Celldex’s Brain Cancer Vaccine Fails Key Phase 3 Test, Shares Fall

Xconomy Boston — 

It’s notoriously tough to develop a successful cancer vaccine, but Celldex Therapeutics has made it farther than most with a closely watched immunotherapeutic treatment for an aggressive, deadly form of brain cancer called glioblastoma. The Needham, MA-based company had even begun building the commercial infrastructure needed to market the treatment, known as rindopepimut (Rintega). But unfortunately today, it’s all for naught. Rindopepimut has failed in a critical late-stage study, leaving its future very much in doubt.

Celldex (NASDAQ: CLDX) said this morning that an independent trial monitoring board has determined that a Phase 3 trial of rindopepimut, or “rindo” in newly diagnosed glioblastoma patients will fail, and as a result, Celldex will stop the study early. Trials can be stopped early for good or bad reasons—either a drug is clearly helping patients or clearly not—and for Celldex it’s the latter. Patients on rintega lived a median of 20.4 months, which is less than the 21.1 month median survival of the control group.

For Celldex’s part, the company said that rindo performed consistently with its prior results, but the control group “significantly outperformed expectations.” Still, rindo’s future as a drug is up in the air. Celldex said it “does not anticipate incurring substantial additional costs” related to the drug’s development as it digs through the data and figures out what to do next. Patients on the drug in the study, prior trials, and compassionate use cases will be offered rindo going forward.

Shares of Celldex plummeted more than 60 percent in pre-market trading Monday.

“We are extremely disappointed for patients that the…study was not successful,” said Celldex president and CEO Anthony Marucci in a statement. “On behalf of Celldex, I want to express our gratitude to the…investigators, patients and families who participated in this trial. While this is certainly not the desired outcome, we remain steadfast believers in the power of immunotherapy to transform the future of cancer treatment.”

Needless to say, the data are a devastating result for Celldex. Rindo is a cancer vaccine that stimulates an immune response against EGFRvIII, a mutated molecule found on tumor cells in about 30 percent of patients with glioblastoma. Because this molecule is only present on tumor cells, the treatment can theoretically kill tumor cells while sparing healthy ones. Rindo is by far Celldex’s most advanced potential cancer treatment, and a positive result in this study—known as ACT IV—would have meant an FDA approval application and the chance to become a revenue generating enterprise in the near future.

In the process, it could have brought a new treatment to a group of patients in desperate need of one. Glioblastoma is an extremely tough-to-treat cancer that often kills people in 15 months or less from the time of initial diagnosis. In a smaller, earlier trial of patients with a recurrent form of the disease, rindo had shown it might help those patients live longer—a survival benefit that increased over time as more data were collected. That type of benefit is something that the study’s lead investigator, David Reardon of Dana Farber Cancer Institute, told Xconomy last year had never been produced by an immunotherapy in glioblastoma, which he said “provide[d] very strong support” that immunotherapy might have a significant impact on the disease the way it has for some other cancers. Celldex executives even floated the idea, at one point, of potentially seeking “accelerated approval”—on a thinner body of evidence than the FDA usually requires—of rindo.

Instead, however, rindo now joins a litany of other potential cancer vaccines like GlaxoSmithKline’s MAGE-A3 and Merck KGaA’s Stimuvax, that have faltered in clinical trials (the only cancer vaccine to win FDA approval was Dendreon’s sipuleucel-T (Provenge)). And Celldex will now have to regroup around a collection of other cancer drugs in earlier studies, like the antibody drug varlilumab and the antibody-drug conjugate glembatumumab vedotin.

There were several potential outcomes for this interim look at the data. The monitors could have stopped the study early because rindo was clearly demonstrating a benefit. They could’ve recommended Celldex finish the study to the end. The third option was what has unfolded today. Many investors clearly have been fearing the worst—Celldex’s shares, which had traded at over $30 apiece last March and over $15 at the end of 2015, have declined considerably as release of the data loomed. They closed at $8.19 apiece on Friday.

In the study, newly diagnosed glioblastoma patients underwent surgery to remove their tumors, then were given radiation and the chemotherapy drug temozolomide. They were then split and randomized into two groups. Half were given rintega and temozolomide, and the others a placebo and the chemo drug. The primary goal was to demonstrate a statistically significant difference in survival in a group of 374 patients with minimal residual disease after surgery.

Celldex will hold a conference call this morning to discuss the results, and its next steps forward.

Here’s more on Celldex, rindo, glioblastoma, and the earlier studies of the vaccine.