Northwest Biotherapeutics, Bristol-Myers Squibb: Success for the Yervoy-Opdivo Combination in CHECKMATE-214 Trial Obviously is a Major Positive for BMY, but also has Important Implications for NWBO (NWBO, Buy, $0.19) (BMY, $60.80, Buy)
The stoppage at an interim analysis of Bristol-Myers Squibb’s’ CHECKMATE-214 trial provides meaningful information into assessing the potential fro success of Northwest Biotherapeutics’ phase 3, DCVax-L trial. CHECKMATE-214 compared a combination the immunotherapy drugs Opdivo and Yervoy to Sutent (standard of care) in previously untreated, advanced or metastatic renal cell carcinoma (RCC). The trial was stopped at an interim analysis because it reached statistical significance on its secondary endpoint of overall survival. The results were not statistically significant on the primary endpoint of progression free survival.
Why is this important to NWBO? Like Checkmate-214, the DCVax-L phase 3 trial has a primary endpoint of progression free survival and a secondary endpoint of overall survival with both endpoints powered for significance. As in CHECKMATE-214, results for immunotherapy drugs have been inconsistent on achieving PFS. As I noted in my recent report, "Northwest Biotherapeutics: Why I Believe That the Phase 3 Trial of DCVax-L in Newly Diagnosed Glioblastoma Patients Has a Very Good Chance for Success", unblinded data from the phase 3 DCVax-L trial indicates that patients appear to be living longer than expected. In that report, I suggested that DCVax-L could be approved even if the trial missed on PFS, if the OS results were encouraging. The results from CHECKMATE-214 reinforce my view.
NWBO has elected to let the phase 3 trial continue even though it has reached the number of PFS and OS events that were prospectively determined to be sufficient to achieve statistical significance. As explained in my report, lengthening the trial increases the potential for statistical significance in OS. There have been questions raised as to why NWBO has not stopped the trial, but having come this far, they want to maximize the potential for success.
This is obviously a positive for BMY as the Company has a huge clinical trial bet that immunotherapy combinations will improve outcomes versus standard of care. This is certainly the case in this trial. These results also augur well for the potential for positive results on OS for BMY’s CHECKMATE-227 trial and Astra-Zeneca’s MYSTIC trial (which earlier missed on PFS). Both of these trials compare anti-PDL-1 and anti-CTLA-4 immunotherapy combinations to standard of care in first line non-small cell lung cancer. The interim readout for both PFS and OS in CHECKMATE-227 could occur by the end of 2017 and the OS results in MYSTIC in 1H-2018. Success in CHECKMATE-227 could have an enormous impact on BMY. It would reestablish BMY as the leader in non-small cell lung cancer over Merck.
I have a Buy on BMY and NWBO.
Tagged as BMY, Bristol-Myers Squibb, CHECKMATE-214 Interim Analysis, DCVax-L phase 3 in newly diagnosed glioblastoma, Northwest Biotherapeutics Inc., NWBO + Categorized as Company Reports, LinkedIn
With all due respect Larry, unless you have some source you can cite, no one knows if NWBO has elected to exceed 233 OS events. Perhaps by a insignificant number, but you speak as if you know they have chosen to exceed 233 OS events.
Also the presentation on June 6, 2017 mentioned that data would be published in the near future. Is it possible NWBO is waiting to release data until the investigators have had the opportunity to publish their articles (which presumably would be pretty soon)?
Wesley Becker
I think that it is a very reasonable hypothesis that NWBO will release more (perhapos a plethora) of additional data concurrent with the release of the inicated report that will deal with observations of invesigators on what is going on in the phase 3 trial. The wolfpack has consistently spun all releases of information in a negative way. Such is their expertise that I beleive they could frame Mother Theresa as a serial killer. Instead of firing rifle shots, NWBO proabably intends to fire a shotgun blast. Of course, the degree of success will hinge on what the report has to say. I don’t know when the report will be published. They alluded to it at ASCO in early June and again last Friday in a presentation by Dr. Boasch at a conference. It should be in the next month or so.
Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
Primary Outcome Measures:
Progression-free survival (PFS) [ Time Frame: Up to 5 years ]
Overall survival (OS) [ Time Frame: Up to 5 years ]
Objective response rate (ORR) [ Time Frame: Up to 61 months ]
-Bristol-Myers Squibb Company (NYSE:BMY) announced today that a Phase 3 study evaluating Opdivo plus Yervoy in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC) met its co-primary endpoint, demonstrating superior overall survival (OS) compared to sunitinib in intermediate- and poor-risk patients.
A poster on Ihub wrote that Share authorization likely can’t be increased at AGM because brokers can’t vote on it, so share count votes would not likely exceed 50% (apparently required) in total, whereas, the poster argues, reverse split is more likely because voters can vote on it. Is this correct? If, as you claim, the company is extending the trial, why would you be recommending a buy now if there is a possibility for a reverse split due to trial extension? Particularly when you were not recommending a buy for a long window during this trial?
Note that the 3rd post shows above that the Checkmate-214 trial has co-primary endpoints of OS and PFS, and was not stopped early based on meeting the secondary endpoint as the article states but was stopped because it met it’s co-primary .
The above poster posed a question regarding your NWBO buy recommendation:
“A poster on Ihub wrote that Share authorization likely can’t be increased at AGM because brokers can’t vote on it, so share count votes would not likely exceed 50% (apparently required) in total, whereas, the poster argues, reverse split is more likely because voters can vote on it. Is this correct? If, as you claim, the company is extending the trial, why would you be recommending a buy now if there is a possibility for a reverse split due to trial extension? Particularly when you were not recommending a buy for a long window during this trial?”
I (and I am sure others) am interested in your response.
Regarding the Co-Primary remark. Due to the cross-over, it makes more sense to have OS as a secondary endpoint, rather than PFS. That way if PFS results and positive and OS results aren’t (due to both groups living longer from the cross-over), then the FDA could still approve on PFS results, and overall high OS results from both groups. And if PFS fails but OS doesn’t then as Larry suggested, the FDA may still approve on just secondary endpoint success.
I don’t know if NWBO is actually keeping the trial blinded longer, however, one reason could be, the fact that there is a cross-over, meaning that both the control and the vaccinated groups are showing longer tails. Therefore, the longer and fatter the vaccinated tail, over the control group tail, the more likely the statistical significance. If overall patients are living longer, then that means the control group is showing a tail as well, therefore to increase the confidence of the group comparison, the longer and fatter the vaccinated group tail, the stronger the efficacy confidence.
Larry, NWBO said this decision was not made one way or the other.
“NWBO has elected to let the phase 3 trial continue even though it has reached the number of PFS and OS events that were prospectively determined to be sufficient to achieve statistical significance.”