Opdivo Development May Have Finally Reached A Roadblock

| About: Bristol-Myers Squibb (BMY)

Summary

BMY's Opdivo (nivolumab) has had major success across a wide spectrum of tumor types, boosting sales into the billions of dollars.

Checkmate 026 was a study executed to see if Opdivo could help lung cancer patients with no prior history of therapy.

Checkmate 026 did not meet its primary endpoint of progression-free survival, but I don't think this stumble will dramatically impact future development of Opdivo.

Bristol-Myers Squibb (NYSE:BMY) has been on a major tear with the immune checkpoint inhibitor nivolumab, receiving approvals in melanoma, lung cancer, kidney cancer and Hodgkin lymphoma. The fact that it does not require a PD-L1 companion test has allowed BMY to capitalize on a wider patient population and gain dominance in this space, despite growing competition from other big pharma companies.

Ever since its approval in recurrent non-small cell lung cancer, BMY has turned its attention to the holy grail: first-line therapy. Currently, many cases of non-small cell lung cancer are treated using chemotherapy, especially in cases that do not have ALK or EGFR aberrations.

The company initiated the Checkmate 026 study in March 2014 to compare chemotherapy to nivolumab treatment in previously untreated patients, with the hope that outcomes could be improved with lower toxicity. Patients were required to have high PD-L1 expression in order to be enrolled.

The News

BMY announced that Checkmate 026 did not meet its primary endpoint of progression-free survival. It is not yet known how badly it failed to meet this endpoint, whether nivolumab was significantly worse than chemotherapy or not.

Dr. Caforio, BMY's chief executive officer, offered the following comment:

"Opdivo has become a foundational treatment that is transforming cancer care across multiple tumor types. While we are disappointed CheckMate -026 did not meet its primary endpoint in this broad patient population, we remain committed to improving patient outcomes through our comprehensive development program, including the ongoing Phase 3 CheckMate -227 study exploring the potential of the combination ofOpdivo plus Yervoy for PD-L1 positive patients, and Opdivo plus Yervoy, or Opdivo pluschemotherapy in PD-L1 negative patients."

This news comes as a bit of a surprise to me, certainly as a disappointment. Nivolumab and other immune checkpoint inhibitors have been shown to help patients in the relapsed setting, with dramatically lower toxicity than chemotherapy. Nivolumab has simply been playing lights out on the court when it comes to immune checkpoint inhibition. It was approved for first-line therapy in melanoma, for example.

Granted, it is important to find out why it failed. If nivolumab has similar efficacy to chemotherapy, but much better tolerability, then there might still be a place for it. However, the language of the press release indicates to me that it the two treatment arms were not equal in terms of efficacy. I will definitely be eagerly awaiting more detailed findings from this study.

What Now?

As Dr. Caforio mentioned, BMY has a number of irons in the fire for first-line treatment using nivolumab. Importantly, the Checkmate 227 study, which is exploring a variety of treatment strategies incorporating nivolumab, will give a clear picture of its role in first-line therapy. Checkmate 227 is comparing the following arms:

  • Nivolumab alone
  • Nivolumab+ipilimumab (PD-L1-positive)
  • Nivolumab+ipilimumab (PD-L1-negative)
  • Nivolumab+platinum-based chemotherapy (PD-L1 negative)
  • Platinum-based chemotherapy

Given the findings of Checkmate 026, it would not surprise me to see a protocol amendment to remove the nivolumab-only arm, but this study should give a good idea of whether nivolumab can help patients in the first line. Combined nivolumab and ipilimumab has been shown in melanoma to improve progression-free survival over monotherapy, with a fair increase in the risk of adverse events.

In conclusion, this is one of the first major stopping points for nivolumab that we've seen so far. It is a testament to the aggression with which BMY is exploring immune checkpoint inhibition that it only took a few years to move from proof of concept to its limits in therapy. Investors should keep an eye out for future studies in lung cancer like Checkmate 227 as well as clinical trials investigating nivolumab in other tumor types. If you are interested, I cover a lot of the news surrounding immune checkpoint inhibitors. Feel free to follow me for more commentary.

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I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.