Merck Confident In Keytruda’s Dominance In Lung Cancer, Despite Competitors’ Data
Executive Summary
With Keytruda sales of more than $3bn during Q3 and roughly 80% market share in lung cancer, Merck indicates little worry about recent data readouts for BMS and AstraZeneca in NSCLC.
Merck & Co. Inc.’s third- quarter revenue growth of 15% was driven largely by its cancer and vaccine portfolios, as Keytruda (pembrolizumab) notched worldwide sales of nearly $3.1bn, good for 62% growth year-over-year. The pharma told its quarterly earnings call on 29 October that it expects Keytruda to maintain its strong market-share hold in lung cancer despite positive readouts in the past week for competing immuno-oncology regimens from Bristol-Myers Squibb Co. and AstraZeneca PLC.
Overall, Merck reported sales of $12.4bn for the third quarter as its vaccines business, headed up by the HPV preventative Gardasil, grew 17% to more than $2.4bn. Gardasil posted sales of $1.32bn, up 26% from one year earlier. But the main focus by both Merck executives and analysts on the call was Keytruda, its growth prospects and the potential of competing regimens that include a CTLA-4 inhibitor in lung cancer.
Chief financial officer Robert Davis noted that Keytruda’s US growth was driven by demand across all its labeled indications. “In squamous and non-squamous first-line lung, Keytruda continues to penetrate all eligible patient populations,” he said. “The survival benefits demonstrated across our four first-line lung cancer trials have firmly established Keytruda as the standard of care in these settings.”
Keytruda’s launches in new indications are encouraging as well, the exec said. “In advanced first-line renal cell carcinoma, we are seeing strong uptake across all three patient risk groups for which we are indicated,” Davis said. “And in adjuvant melanoma, the positive momentum continues since our approval earlier this year.” (Also see "Keeping Track: US FDA Approves Esperoct, Tightens Chantix Label, Starts Review Of Alder’s CGRP Candidate " - Pink Sheet, 24 Feb, 2019.)
For the first nine months of 2019, Keytruda sales totaled $7.97bn globally, up 59% from the $5.02bn posted during the first three quarters of 2018. Outside the US, Keytruda sales rose 75% during the third quarter, with lung cancer again the driver, Davis said.
BMS caught attention on 22 October with its announcement that its Checkmate-9LA study had demonstrated that combination therapy with its anti-PD-1 agent Opdivo (nivolumab) and its CTLA-4 inhibitor Yervoy (ipilimumab) plus two cycles of chemotherapy offers a better overall survival benefit than chemotherapy alone in first-line non-small cell lung cancer. (Also see "An Early Surprise Win For BMS’s Opdivo/Yervoy In Lung Cancer" - Scrip, 22 Oct, 2019.) Like the earlier Checkmate-227 data, which showed the combo’s potential in the first-line setting as a chemo-free option, BMS is hoping these data may help boost sales of Opdivo, which was the top-selling IO drug before Keytruda passed it (see chart).
Another potential shot across Keytruda’s bow came on 28 October, just one day before Merck’s earnings call, AstraZeneca reported that the POSEIDON study, testing its PD-L1 inhibitor Imfinzi (durvalumab) with its experimental CTLA-4 inhibitor tremelimumab, met its primary endpoint of progression-free survival in first-line NSCLC. (Also see "POSEIDON Delivers For AstraZeneca's Imfinzi, But More Clarity Is Needed" - Scrip, 28 Oct, 2019.)
Merck Confident In Its Data, Real-World Experience
Merck Research Laboratories president Roger Perlmutter told the earnings call that while Merck has long anticipated that other companies will try to demonstrate utility in first-line NSCLC, “the set of studies that we have already performed provide an enormously strong foundation for the treatment of non-small cell lung cancer.”
He also addressed speculation of whether Merck’s ongoing study combining Keytruda with BMS’ Yervoy could offer a new avenue for both companies.
“All of us are eager to understand whether anything else could be added to Keytruda,” Perlmutter said. “But thus far, we don’t really have any data that supports that. Our own study, our [KEYNOTE-598] study with Keytruda and ipilimumab will provide, we hope, definitive information on whether [that combination] actually improves results as compared to what it seen with Keytruda alone. Thus far, it’s kind of a mixed bag from what we can see.”
He added that without numerical data from the Checkmate-9LA and POSEIDON studies – which have only reported top-line results so far – Merck can’t really compare those regimens to Keytruda. Both trials are expected to be presented at upcoming medical meetings.
The KEYNOTE-598 study isn’t slated to read out until 2023, although Merck also has its own CTLA-4 antibody, MRK-1308, in Phase I.
Merck’s chief commercial officer Franklin Clyburn emphasized Keytruda’s standing in the US as the standard of care in first-line NSCLC. “Approximately eight out of every 10 eligible patients are receiving a Keytruda regimen, either a monotherapy or in combination,” he said. “And what we’re hearing from both the academic community … and the community physicians is that they really believe Keytruda has now established itself as a standard of care in lung.
“I think also, importantly, we have to note that there’s significant real-world experience based on our first-mover advantage with Keytruda in lung,” Clyburn continued. “So, while we know it’ll be eventually competitive in this space, we feel very confident in our position.”
Analysts Take “Wait And See” Stance On Competitor Studies
SVB Leerink analyst Daina Graybosch questioned in a 29 October note how much of a threat the competitor trials pose for Merck right now. “Feedback from our August survey of medical oncologists treating NSCLC suggests an all immuno-oncology regimen (such as Opdivo + Yervoy) could have utility in patients that cannot tolerate chemotherapy, which could be a niche for the combination,” she wrote. She added however, “Keytruda currently has a roughly 80% share of the first-line NSCLC market in the US, and we agree with Merck that this lead will be difficult to dislodge given the high barriers [that] physician familiarity and real-world experience provide.”
Morningstar analyst Damien Conover concurred in a same-day note: “We are skeptical that the forthcoming detailed data behind the [BMS and AstraZeneca] studies will provide strong enough data to displace Merck’s entrenchment.”