Immune checkpoint inhibitors are currently setting the oncology world on fire, with recent approvals in melanoma, lung cancer, renal cancer and Hodgkin lymphoma. While Bristol-Myers Squibb (NYSE:BMY) currently leads the pack in most of these tumors, Merck (NYSE:MRK) is one of several other competing developers of anti-PD-1/PD-L1 antibodies. The MRK entry to the race, pembrolizumab, is currently approved for the treatment of metastatic melanoma. It is also approved to treat patients with relapsed lung cancer, as long as the tumor has overexpression of PD-L1, the ligand of PD-1.
BMY has been one step ahead of MRK in developing its PD-1 antibody, nivolumab, for first-line treatment of lung cancer. In CheckMate 012, nivolumab was given to patients with advanced non-small cell lung cancer (NSCLC). This showed favorable response rates and highly durable remissions, stoking the fire for a randomized, head-to-head trial against chemotherapy. Trials like CheckMate 026 are ongoing to address this question, but no results have been presented.
Thus, it is with some well-deserved fanfare that MRK has presented a press release to the public stating that the results of KEYNOTE-024, a phase 3 study comparing chemotherapy to pembrolizumab in PD-L1-positive patients, has met its primary endpoint of progression-free survival.
Details are quite limited in the press release; however, the company stated that both progression-free survival and overall survival were significantly better in the pembrolizumab arm than in the chemotherapy arm.
Impact on the race
Several times now, pembrolizumab has beaten nivolumab to market. In the case of lung cancer, however, this has come at a cost. Clinicians are only allowed to use pembrolizumab with patients who test positive for PD-L1 expression.
This has allowed BMY to take a significant portion of the market opportunity, with sales of nivolumab doubling those of pembrolizumab.
If pembrolizumab is made available for first-line treatment of lung cancer, however, it may help to gain some of that market opportunity back.
Some astute readers may still argue, though, that the need to test positive for PD-L1 will hinder the introduction of pembrolizumab. This is in part because testing for PD-L1 remains controversial. Without a doubt, patients who are positive have higher response rates with these therapies.
But PD-L1 negativity does not necessarily mean you will not respond, either. What's more, each PD-1/PD-L1 therapy (nivolumab, pembrolizumab, avelumab, atezolizumab, durvalumab) has its own companion diagnostic test, and these have yet to be harmonized. All in all, it has created a lot of confusion, so the need to test for PD-L1 with pembrolizumab is not a net positive for sales.
But it's worth noting that the first-line nivolumab study comparing to chemotherapy is enrolling only patients with PD-L1-positive tumors, as well. So if nivolumab is successful in this setting, its approval will almost certainly also be based on PD-L1 testing.
As such, if MRK can gain the first approval advantage, it may be able to carve out a larger portion of the market space.
What's more, if nivolumab and pembrolizumab are both approved, it would mean good things for patients, as clinicians can take into account the differences in toxicity risk between the two agents when trying to decide on therapy. The fact that both are much safer than chemotherapy is already a boon, but soon patients with newly diagnosed NSCLC may have two powerful options for therapy.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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.