The data displayed by Mercury’s I-O star Keytruda on the ASCO 2018 is amazing, and almost everyone believes that Keytruda has no doubt seized the throne of lung immunotherapy. However, competitors do not seem to agree with this. In their view, the difference between their drug and Keytruda is very small, or there is no difference at all.
Dan Chen, vice president and global head of cancer immunotherapy development at Genentech, believes that PD-1 and PD-L1 therapy are “very similar” to the data he sees.
“Is there a difference between Roche’s Tecentriq, AstraZeneca’s Imfinzi, BMS’s Opdivo and Keytruda? Perhaps there are, but the difference between them may be very small,” Dan Chen asked himself, “Statistically, if They are all the same, and you may want to know the difference in clinical trials.”
Giovanni Caforio, CEO of Bristol-Myers Squibb, said in an interview with foreign media CNBC that it was more straightforward. “When you see the whole data… Keytruda and Opdivo, there is really no difference between the two drugs. ”
Considering the pressure that Keytruda’s growing number of favorable data bring to competitors, these two people are completely understandable. However, Merck is still firmly determined that his product is slightly better.
“Do all PD-1/PD-L1 drugs are evenly matched?” When FiercePharma, a medical media specialist, threw this out, the senior vice president of Merck and Roy Baynes, head of global clinical development, calmed down, “I think we Need data to make a conclusion.”
Investors are more concerned about these data than anyone else. They want to know whether Roche and BMS can catch up with Merck, after all, the latter has obtained survival benefit data in 5 randomized controlled lung cancer trials.
Although Roche also published positive statistics for Tecentriq on squamous lung cancer at ASCO, BMS also highlighted Opdivo’s outstanding performance in the new biomarker population. But since Keytruda’s latest victory masked the light of the first two, investors’ enthusiasm for the two companies was clearly inferior to that of Merck.
Dan Chen said that the current illusion that the three drugs cause great differences among people should be attributed to the design of clinical trial programs. Merck East’s Keytruda single drug won the first-line treatment of lung cancer, and Opdivo failed, not excluding the latter using a “backup” mechanism. “The operational strategies of these clinical studies have many differences,” he added. “It is more important to look at the overall evidence. For example, Tecentriq’s data in the three first-line lung cancer studies is also positive.”
However, the evidence obtained by the analysts does not seem to endorse Dan Chen’s view that there is no difference in the PD-1/PD-L1 drugs. For example, the FDA stopped the clinical trials of Keytruda’s treatment of patients with multiple myeloma 1 year ago (Keynote-183 and Keynote-185 studies), but recently released the clinical duration of the Opdivo treatment of multiple combination myeloma trials. This move may indicate that “the outside world simply believes that PD-1/L1 drugs are similar, or interchangeable,” which is incorrect.
At the same time, market observers have so far failed to identify the causes of failure of some PD-1/PDL1 drugs. Including the FDA’s accelerated approval of Keytruda for head and neck cancer, Keytruda failed in a phase III clinical (KN012); similarly puzzling failures included Opdivo’s Phase III clinical CM026 trial for lung cancer, and Tecentriq’s Phase III clinical trial of IMvigor211 test for bladder cancer.
“Last year I said that there were at least two different tumor indications that succeeded on Merck, while other companies failed… Do not rule out the possibility that Merck’s clinical trial strategy is better than other companies’. “This year, Keytruda is the only PD-1 drug that shows the survival advantage of monotherapy in lung cancer first-line therapy, and in all PD-1/PD-L1 with bladder cancer, only,” said Umer Raffat, an analyst at Evercore ISI. Keytruda showed a survival advantage in second-line bladder cancer. Is it possible that the clinical outcome is not consistent due to subtle differences in the drug itself? Now it does not seem to rule out this possibility.”