OncoMed Pharmaceuticals Inc. (Redwood City CA) began the week with a combination punch that some say spells a knockout in the near future. In back-to-back statements, OncoMed revealed that its Celgene Inc.-partnered lead asset had bombed a Phase 2 pancreatic cancer trial and Germany’s Bayer AG had walked away from two drugs, triggering a 45% drop in its stock price to $4.84 late in the week.#OncoMed hit with a combination punch that some say spells a knockout in the near future Click To Tweet
News of the failed clinical trial landed first and did the most damage. The trial enrolled 204 patients with metastatic pancreatic cancer and randomized them to one of three arms. All participants received Abraxane and gemcitabine. One arm received placebo on top of this regimen, while the other two took different courses of OncoMed’s experimental demcizumab. The top-line findings are devoid of reasons to be optimistic about the anti-DLL4 antibody, says FiercePharma.
Against most measures, the placebo group at least matched the experimental treatment arms. At 5.5 months, the progression-free survival seen in the placebo arm was identical to the result from the pooled treatment cohorts. That is a high point for the treatment arms.
The demcizumab arms had a median overall survival of 13.2 months. The placebo group is yet to reach its median overall survival. To finish off the losing streak, the overall response rate in the demcizumab groups came in at 33.1%, eight percentage points lower than that achieved by the placebo regimen.
The only endpoint against which OncoMed could point to numerical superiority for demcizumab was a measure that combined complete responses, partial responses and stable disease. Close to 75% of subjects in the demcizumab arm met this definition of clinical benefit, compared to 71% of patients in the placebo group.
With the data suggesting demcizumab has come to the end of the road in pancreatic cancer, the drug’s future, if it has one, and ability to generate some of the $3 billion in milestone committed to by Celgene will likely lie in other indications. OncoMed is testing demcizumab as a treatment for non-small cell lung cancer.
“Based on the lack of benefit over standard-of-care, which performed remarkably well, we will be discontinuing this trial. We will also discontinue any additional enrollment in our other ongoing demcizumab trials and conduct analyses of the data from those trials as planned,” OncoMed CEO Paul Hastings said in a statement. “OncoMed remains focused on completing and analyzing the results of the two randomized Phase 2 clinical trials, PINNACLE and DENALI, that are anticipated in the first half of this year.”
With the latest failure coming 15 months after an interim assessment found another candidate was coming up short in a pancreatic cancer trial, the pressure is now on OncoMed to deliver positive news on its earlier-stage assets. In the case of vantictumab or ipafricept, OncoMed will need to do so without the support of Bayer.
The German pharma colossus added injury to insult, notifying OncoMed that it decided not to exercise its option on the biotech’s Wnt pathway inhibitors vantictumab (anti-Fzd, OMP-18R5) and ipafricept (Fzd8-Fc, OMP-54F28) for “strategic reasons.”
OncoMed’s near-term survival hopes now rest on the above-mentioned Phase 2 studies, PINNACLE and DENALI, that are due to read out later in this quarter.
Talk about a Bad Day at Black Rock, except this time in Redwood City, CA. In the face of two roundhouse haymakers, you have to give OncoMed credit for sheer gumption. After Bayer followed the grim news about the failure of demcizumab for pancreatic cancer with the decision not to exercise an option to license two of the US company’s other experimental therapies, OncoMed still tried valiantly to put a positive spin on the news.
And this was just a year after its number two drug also flunked a Phase 2 trial. Then the biotech followed up with the news that Bayer is bypassing a tie-up on two other key programs, completing a one-two punch.
The mid-stage study of demcizumab was an embarrassing failure for the primary as well as the key secondary endpoint in the study of metastatic pancreatic cancer–admittedly a very tough field in cancer R&D. Combining demcizumab with Abraxane and gemcitabine in untreated patients essentially mirrored the PFS (pancreatic fluid collections) results for the comparative triple that replaced OncoMed’s drug with a placebo, says Endpoints.
The median overall survival (OS) rate in the demcizumab arm, meanwhile, hit 13.2 months, while the placebo group hasn’t yet reached a median OS rate. The overall response rate was 33.1% in the drug triple, compared to 41.2% in the comparator arm.
“Based on the lack of benefit over standard-of-care, which performed remarkably well, we will be discontinuing this trial. We will conduct additional analyses, together with our partner, Celgene, to understand these outcomes. We will also discontinue any additional enrollment in our other ongoing demcizumab trials and conduct analyses of the data from those trials as planned,” said OncoMed CEO Paul J. Hastings.
Celgene paid $177 million up front and promised more than $3 billion in milestones to gain co-marketing rights to demcizumab in 2013. That deal helped establish OncoMed as a biotech to watch, with a spotlight on their lead cancer stem-cell therapy.
“Pancreatic cancer has proven to be a uniquely challenging disease, and these data appear to reflect some of those disease and treatment complexities. The safety data seen in the YOSEMITE trial were generally consistent and in line with our expectations. We continue to analyze these data, and look forward to presenting the full study findings at a future scientific congress,” said Robert Stagg, Senior Vice President of Clinical Research and Development.
But outside the company, are there any signs of life left in the development of demcizumab?
Turns out the answer is “yes” as HC Wainwright’s Shaunak K. Deepak maintains a Buy rating on OncoMed, with a price target of $9–over twice its current price. The analyst believes that this news “does not necessarily mean the development of these assets is over.”
As mentioned above, OncoMed expects to report data from its discontinued Phase 2 DENALI trial for demcizumab in non-small cell lung cancer later in the quarter, along with preliminary data from the Phase 1b study, although Deepak believes that this would be unlikely following the failure of the YOSEMITE trial.
On the other hand, Deepak lowered the probability of successful development of demcizumab from 30% to 10%.
OncoMed is also testing demcizumab in combination with Merck’s Keytruda as a treatment for a type of lung cancer, having already stopped another lung cancer study testing demcizumab.
An analysis of both studies is expected to be submitted to Celgene which can opt into the program. But “given YOSEMITE results, we think opt-in is unlikely,” Leerink’s Michael Schmidt said. Finally, YOSEMITE may have failed but other potential value drivers remain, Wells Fargo analysts said in a note.Steve's Take: #OncoMed hopes for better trial data late in year and masking current debacle Click To Tweet
A double dose of black news and OncoMed’s CEO Paul Hastings almost cheerfully says, we’re not dead yet. And several analysts think he’s right. Investors, on the other hand, bailed in droves.
Biotech clearly is not for the timorous and faint-hearted. Kudos to Mr. Hastings for keeping a steady hand on the OncoMed helm as it heads toward another round of trial data later this year and perhaps some good news that makes this week’s debacle fade into the desert sunset.