GSK experienced an eventful 2022. The British drugmaker officially spun out its consumer health joint venture with Pfizer. And the company’s flagship vaccines business appears to be on the mend. But its burgeoning oncology portfolio suffered multiple setbacks.
On the sidelines of the J.P. Morgan Healthcare Conference, Fierce Pharma sat down with GSK’s chief commercial officer Luke Miels, who recently took on additional responsibilities in vaccine strategies.
A wide range of topics were discussed, including GSK’s preparation for upcoming FDA decisions for its RSV vaccine, potential first-in-class chronic kidney disease (CKD) anemia drug daprodustat and newly acquired JAK inhibitor momelotinib, as well as the company’s decisions to either withdraw or limit the use of cancer drugs Blenrep and Zejula. And an upcoming phase 3 readout for a combination of Zejula and GSK's PD-1 inhibitor Jemperli has, as Miels put it, a low chance of success. GSK’s mRNA vaccine collaboration with CureVac and the company’s appetite for additional M&A deals were also included.
1. COVID-19 and influenza mRNA vaccines opportunity
Background: After an initial setback with their mRNA COVID vaccine, GSK and partner CureVac came back a few days ago with positive preliminary data for their modified COVID and flu shots. But the question is, with entrenched mRNA players Pfizer-BioNTech and Moderna, is there any room left for another COVID shot?
Miels: “For COVID? Limited. But I think the real interest is in the COVID-flu combination, where I think there is a sizable market opportunity.” Under the deal structure, GSK would capture 90% of the asset’s value. If the mRNA COVID-flu vaccines are successful, the whole COVID market and “a large part” of the flu shot market will covert to the combo because “people prefer one shot instead of two.” To convince people to convert, the COVID component of the combo needs to be “as good as or better than current options.” As for the flu element, the mRNA technology allows for longer time to study the flu season to better choose the dominant strain for the vaccine construct. It also allows for more strains to be included than the current quadrivalent options. MRNA vaccines' tolerability profile could be a challenge in the flu setting, but there's “heavy overlap” between COVID and flu shots takers.
2. RSV vaccine competition
Background: GSK's application for an RSV vaccine for adults 60 years and older is under FDA priority review, with a decision expected by May 3. Pfizer has a candidate targeting the same population also under priority review for a verdict in May. Furthermore, Pfizer touted positive data for its maternal vaccine to protect newborns, but GSK's maternal effort hit a safety hiccup.
Miels: GSK will initially focus on high-risk individuals for the RSV launch. There are “a lot of parallels” between RSV and shingles in that vaccine makers need to create an “explained demand” because no RSV preventive solutions were available. But awareness is increasing, and COVID taught people with underlying diseases that they are also at a higher risk of developing serious complications from respiratory diseases, and they could therefore be motivated to get an RSV shot. GSK hopes RSV vaccines could match the penetration levels seen with flu shots. Between the two populations, older adults currently represent a bigger market than newborns. (During the Q&A session after GSK's presentation at JPM, Miels said doctors see “distinct difference” between Pfizer's and GSK's candidates in high-risk patients. The “biggest variable” in its competition with Pfizer right now, Miels said, is whether a vaccine could offer protection longer than one year, and GSK expects to have data on that before its final payer discussions in June.)
3. Blenrep withdrawal and momelotinib launch
Background: GSK's oncology ambition took a serious hit late 2022 when Blenrep failed as a monotherapy in a confirmatory phase 3 trial. GSK immediately pulled the BCMA-targeted agent's accelerated approval at FDA’s request but put up a bold front for its two phase 3 trials testing a lower Blenrep dose in combinations. Readouts are expected in the first half. Also in blood cancer, GSK’s application for JAK inhibitor momelotinib in myelofibrosis is awaiting an FDA decision by June 16. GSK got momelotinib from its $1.9 billion acquisition of Sierra Oncology last year and, at the time, touted the med's fit with Blenrep in hematology.
Miels: GSK has kept the commercial team behind Blenrep in place for a potential momelotinib approval. About 75% of multiple myeloma doctors also treat myelofibrosis. With Blenrep, the problem is about finding the right dose. The FDA has told GSK the original monotherapy dosage is too high. The soon-to-report DREAMM-7 and DREAMM-8 combo trials could find the optimal dose for Blenrep, and GSK looks to reintroduce the drug if trials are positive.
4. Zejula setbacks and market position
Background: The FDA recently took issue with concerning patient survival data coming from PARP inhibitors in some ovarian cancer settings. As part of the classwide scrutiny, GSK pulled a Zejula late-line indication and narrowed its second-line maintenance use to just ovarian cancer with BRCA mutations. Despite a broad label in all ovarian cancer patients who've responded to initial chemotherapy treatment, Zejula has mostly only been able to reach patients without homologous recombination deficiency (HRD), while AstraZeneca and Merck's Lynparza continues to hold the lion's share of the HRD-positive market—more specifically, the BRCA-mutant subgroup—in the first-line maintenance setting.
Miels: The label reduction affects 20% of Zejula's sales. But it also allows GSK to have another discussion with physicians to try to convince them to use Zejula early in the first-line setting to reap the maximum benefit for patients. The “bulk of physicians” don't extrapolate results in the later-line trials to newly diagnosed patients, and they recognize patient crossovers are a big problem that could muddy the results to the Zejula arm's detriment. Zejula currently captures 50% of new patient starts in first-line maintenance treatment. In doctors' minds, the GSK drug is perceived more as a therapy for nonmutant cases. Lynparza's overall survival data, longer time on the market and broader indications in multiple tumor types make doctors' positive opinions toward Lynparza “difficult to dislodge,” and the current market dynamics will likely stay “static.” GSK also expects a 2023 readout from an adaptive phase 3 trial called FIRST that tests Zejula in combination with GSK's PD-1 inhibitor Jemperli. The study has a very low chance of being successful because ovarian cancer isn't immunogenic. But if that study turns out positive, “that could change people's mind” of Zejula.
5. Jemperli's future
Background: GSK recently showed that Jemperli could match up to Keytruda in their respective combinations with chemo in newly diagnosed nonsquamous non-small cell lung cancer in the phase 2 PERLA trial. Data on tumor shrinkage and delaying tumor progression actually favored Jemperli, though the trial wasn't powered to show statistically significant superiority. Separately, in a small academic-sponsored trial readout that somehow captured the attention of the likes of The New York Times, Jemperli eradicated tumors in all 14 patients with mismatch repair-deficient locally advanced rectal cancer. The results, while not actionable from a regulatory standpoint, could potentially boost Jemperli's competitive edge as a latecomer in the crowded PD-1/L1 space.
Miels: “We're not expecting to replace [Keytruda] in the first line. But we did [the PERLA trial], because we wanted to validate in physicians' minds and the FDA's mind that these are comparable.” Those data could help change Jemperli's prescriber base, and PERLA offers GSK a clinical and regulatory pathway to get further approvals for Jemperli in combinations with TIGIT and CD96 inhibitors. Currently, most Jemperli use is in second-line endometrial cancer, but GSK expects a phase 3 readout in first-line endometrial cancer in the first quarter.
6. Daprodustat decision in CKD
Background: The novel HIF-PHI class of oral drugs for anemia in CKD once bore high hopes to displace erythropoietin stimulating agents. But safety signals have derailed two agents, and now it’s up to GSK’s daprodustat. The FDA once again raised cardiovascular safety concerns around daprodustat. During an advisory committee meeting, FDA’s external experts voted in favor of the GSK drug in dialysis-dependent anemic CKD patients but recommended against it in nondialysis population.
Miels: If dapro is approved only in dialysis patients, GSK doesn’t plan to run any additional trials to try to resurrect the nondialysis indication. In that scenario, GSK’s commercialization strategy will focus on contracting with dialysis providers. If, in the low chance that dapro also receives an approval in the nondialysis population, it will be a “classical cardiometabolic product launch,” including field force detailing.
7. M&A appetite
Background: GSK narrowed its focus on innovative medicines and vaccines with the spinoff of consumer health venture Haleon. The new GSK’s M&A moves have therefore become a focus among investors. Apart from striking licensing deals like that with CureVac, GSK bought Sierra Oncology for $1.9 billion and took in pneumococcal vaccine developer Affinivax in a deal worth up to $3.3 billion.
Miels: GSK will continue to look for acquisitions in that ballpark. Sierra is a great “template deal” for GSK; i.e., in the $1 billion to $2 billion range. “My preference is to do a whole series of deals in that range.” The size may be bigger, “but you’re not going to see us going out and doing Horizon-type transactions.” (In the largest biopharma deal of 2022, Amgen will purchase Horizon Therapeutics for $27.8 billion.) GSK is agnostic about therapeutic areas, but the company intends to focus more on late-stage assets.