MSD and Moderna are vying for the approval of their jointly developed personalised cancer vaccine, intismeran autogene, after the therapy became the first to demonstrate additive benefit over Keytruda (pembrolizumab) monotherapy in the adjuvant melanoma setting.
The pair will seek approval for the jab following the positive outcome of the INTerpath-001 study (NCT05933577), in which 1,137 patients with Stage IIb-IV melanoma who had undergone complete surgical removal received either a combination of intismeran autogene and Keytruda (pembrolizumab) or Keytruda alone post-surgery, the latter being the current standard of care (SoC) in this setting.
During the trial, patients receiving the combination regimen experienced statistically significant improvements in both recurrence-free survival (RFS) versus the Keytruda monotherapy group, meeting the trial's primary endpoint.
Alongside its impact on RFS, intismeran autogene plus Keytruda also significantly enhanced distant metastasis-free survival (DMFS) compared with Keytruda alone – thus meeting the trial's key secondary endpoint.
Patients also tolerated the combination well, with researchers identifying no new safety signals linked to intismeran autogene-Keytruda.
The results of the INTerpath-001 mark the first time researchers have obtained positive Phase III data for an mRNA-based, individualised neoantigen therapy (INT) in oncology. Moderna added that intismeran autogene is the first therapy to demonstrate an additive benefit over Keytruda monotherapy in the adjuvant melanoma setting.
Intismeran autogene is an investigational, personalised mRNA-based cancer vaccine that is custom-built using a patient's own tumour tissue to target neoantigens to train the immune system to fight specific cancer cells.
In a statement covering the readout, principal investigator and medical director of the Melanoma Institute Australia, Georgina Long, noted these results highlight intismeran autogene-Keytruda's potential to establish "a new treatment paradigm" for patients with adjuvant melanoma as Keytruda remains the go-to option in this setting.
The initial outcomes of the INTerpath-001 trial will be gladly welcomed by both MSD and Moderna, which are currently taking steps to enhance their portfolio offerings. The companies make these efforts as the former equips itself to offset losses linked to the looming patent expiry of its best-selling asset, Keytruda, while the latter contends with waning sales of its Covid-19 vaccine portfolio.
It appears that MSD and Moderna are not the only ones pleased with the outcome, as Moderna's stock soared 84% from $62.96 at market close on 18 August to $116.25 at opening on 19 August, while MSD's stock value grew nearly 9% during the same timeframe.
Moderna's stock has continued to fly higher during the day, reaching $141.78 by 11.30am ET.
With a late-stage win in the bag, many analysts are touting the strong future commercial promise of intismeran autogene – not just within the melanoma space, but across the wider solid tumour space.
According to Jefferies analysts, Wall Street is "likely to ascribe multibillion peak sales potential" to intismeran autogene's potential in melanoma alone, while highlighting the potential positive readthroughs to the drug's potential in the eight other mid-to-late-stage programmes Moderna and MSD are running involving the drug in other significant indications like bladder cancer and non-small cell lung cancer (NSCLC).
Meanwhile, GlobalData oncology analyst, Biswajit Podder, touts the INTerpath-001 outcome as highly encouraging. "In my view, it represents one of the strongest validations so far of the personalised cancer vaccine concept," he comments.
If the full Phase III data set confirms a clinically meaningful benefit across disease stages and relevant patient subgroups, Podder believes the combination has a "realistic chance" of becoming the new SoC for suitable patients with high-risk resected melanoma.
However, he caveats that actual hazard ratios, absolute benefit, subgroup data and, importantly, whether an overall survival (OS) advantage eventually emerges are yet to be seen. In his eyes, the larger, long-term opportunity lies in whether Moderna can replicate this impact in other tumour types.
While some believe intismeran autogene could become a potential gamechanger, Podder notes that MSD and Moderna will need to overcome challenges around individualised manufacturing and efficient delivery of such a therapy at scale.
Experts interviewed by Clinical Trials Arena's parent company, GlobalData, also voiced their concerns around the manufacturing challenges, as intismeran autogene is complex and expensive to produce – potentially presenting both logistical and access challenges for certain regions of the world.
"MSD and Moderna eye cancer vaccine market debut on Phase III melanoma score" was originally created and published by Clinical Trials Arena, a GlobalData owned brand.