There's bad news out of Celldex Therapeutics (CLDX - Get Report) Monday morning. The pivotal brain tumor clinical trial involving the company's experimental cancer vaccine Rintega was stopped for futility.
Celldex was informed of the failure of the Rintega phase III study known as ACT IV on Friday evening following an interim analysis conducted by independent data monitors. The study enrolled patients with a certain type of glioblastoma multiforme (GBM), an aggressive brain tumor.
At the interim analysis, Rintega was found to reduce the risk of death by just 1% compared to the control arm. However, at the median, Rintega-treated patients fared worse, surviving 20.4 months compared to 21.1 months for the control arm, the company said.
As a result, Celldex is discontinuing clinical development of Rintega. Obviously, the company's plans to seek approval for the product in the U.S. or Europe are also being shelved.
Celldex shares are getting crushed, down 59% to $3.37 in premarket trading. The stock closed Friday at $8.19, down 48% for the year already because of the biotech bear market and investor skittishness about owning the stock ahead of the Rintega study interim analysis.
How much Celldex's stock price declines now that Rintega has blown up will depend on the value investors place on the rest of the company's cancer drug pipeline. The most advanced drug in Celldex's pipeline is glembatumumab vedotin, an antibody drug conjugate being studied in a randomized clinical trial enrolling triple-negative breast cancer patients. Patient enrollment into this study is expected to be completed in the second half of the year.
Then there's varlilumab, Celldex's monoclonal antibody targeting CD27, which is being run through a series of early-stage clinical trials of solid tumors. Some of these studies pair varlilumab with Bristol-Myers Squibb checkpoint inhibitor Opdivo.
Celldex ended 2015 with $290 million in cash. The company's enterprise value coming into Monday was just above $500 million.
Rintega is a cancer "vaccine" meaning it was designed to educate a patient's immune system to identify and kill certain cancer cells. Rintega's target was a mutated protein known as EGFRvIII (v3), found in about 30% of GBM brain tumors but absent from healthy tissue. Brain tumors containing high levels of EGFRvIII grow more aggressively and are difficult to treat.
In the ACT IV study, 745 patients with newly diagnosed and EGFRvIII-positive GBM underwent surgery to remove their tumors, followed by standard radiation and chemotherapy. Once that baseline treatment was completed, the patients were randomized into one of two arms: Half the patients received injections of Rintega along with standard chemotherapy maintenance; the other half of patients received a control injection plus standard chemotherapy. The primary endpoint of the study was overall survival, which was not met.
Last year, Celldex reported results from a study in which Rintega, when combined with Roche's Avastin, prolonged survival in patients with recurrent GBM. These data, however, were not strong enough to convince the Food and Drug Administration to allow Celldex to file for approval.
Cancer vaccines, particularly those targeting GBM, have a dismal track record. There was hope Rintega would be the exception, but no longer. The failure of Rintega follows negative study results for ImmunoCelluar Therapeutics' GBM vaccine ICT-107 in 2013. Northwest Biotherapeutics is developing a GBM vaccine known as DCVax, but a phase III study has been stalled since August due to an unexplained patient enrollment halt.
If GBM patients can be helped by immunotherapy, it will likely depend on the outcome of ongoing clinical trials of checkpoint inhibitors like Bristol's Opdivo and Merck's Keytruda.Provenge, a prostate cancer vaccine, is the only approved cancer vaccine on the market but the company which developed it, Dendreon, went bankrupt trying to sell it. Provenge was later acquired by Valeant Pharmaceuticals.