After sitting through the full presentation on the Phase 3 INTerpath-001 trial at the ESMO Congress over the weekend, analysts are more keen on the personalized mRNA cancer vaccine data that last week spurred a stock selloff for both partners.
With Merck and Moderna days removed from a data leak and the conference presentation in the rearview, analysts have softened on the partners’ personalized mRNA-based cancer vaccine, with many now agreeing that the treatment combo elicited an acceptable reduction in the risk of death or recurrence.
On Thursday, data from Merck and Moderna’s Phase 3 INTerpath-001 trial was published early after it leaked online ahead of a Saturday presentation at the European Society of Medical Oncology (ESMO) meeting in Spain. Intismeran autogene, when paired with Keytruda, reduced the risk of recurrence or death by 42%, with a hazard ratio of 0.58 in patients with resected stage 2b to 4 melanoma. The study included 1,137 patients.
The leak spurred a selloff for both Moderna and Merck, with some analysts expressing disappointment that the hazard ratio only just cleared the 0.60 mark some had noted as the desired range. (A lower hazard ratio translates to lower relative risk.)
“The data leak on Thursday, October 22, stole some of the thunder here but INTERPATH-001 is a quality interim dataset in a relevant treatment setting where nothing prior has shown benefit beyond PD-1 checkpoint inhibitor monotherapy, and not due to a lack of trying,” William Blair said in a Monday morning note.
BMO Capital Markets agreed. “From this data it is clear adding intismeran to adjuvant pembrolizumab [Keytruda] lowered the risk of recurrence or death (RFS HR 0.58), providing a meaningful benefit to patients over pembrolizumab-only adjuvant therapy,” the firm wrote on Sunday.
Still, Moderna’s shares declined 7% in premarket trading to $185.75 on Monday morning. The stock is still up 700% year to date, however, according to William Blair.
During the presentation, analysts got more details as expected. William Blair noted that the hazard ratio was down to 0.42 when examined six months or more post-therapy, when the vaccine is expected to have a greater impact.
William Blair noted that the presenter, Inge Marie Svane from Copenhagen University Hospital, “was pretty measured” on the results, acknowledging the lack of overall survival (OS) data at this point in the trial. But the firm is confident that OS simply hasn’t been reached yet. The same is true for an ongoing Phase 2b KEYNOTE-947 trial of the intismeran/Keytruda combo, which is at five years of follow up. The study has, however, shown a 53% risk reduction trend, William Blair said.
Still, BMO had some reservations on how intismeran will fit into clinical practice. Bristol Myers Squibb will pose a major challenge, the firm elaborated, with the immuno-oncology combo Opdivo and Yervoy previously showing an event-free survival rate hazard ratio of 0.32 during the Phase 3 NADINA trial. This trial cannot be compared apples-to-apples to Merck and Moderna’s new dataset, BMO cautioned, but BMS’ result “sets a compelling standard for the disease.”
The NADINA trial, however, had a higher rate of adverse events, with 30% of patients experiencing serious treatment-related adverse events, compared to 10% for the INTERPATH-001 trial.
“This likely positions intismeran as the preferred treatment for those who are less likely to tolerate dual checkpoint blockade,” BMO wrote. “With no head-to-head data, we expect the choice between approaches to be made physician by physician for now.”
Elsewhere at ESMO, Moderna presented early-stage open label data for intismeran plus chemo in pancreatic cancer, showing that 55% of patients had not relapsed at 17 months of follow up, according to Jefferies. This gave investors a peek at how the vaccine might perform beyond melanoma, the firm added.
More than three potentially registrational datasets for intismeran are expected over the next 14 months, including in renal cell carcinoma, bladder and lung cancer, Jefferies noted on Sunday.
