Dive Brief:
- An individualized cancer vaccine developed by Moderna and Merck & Co. hit its main goals in a Phase 3 trial, helping delay disease recurrence in people with melanoma as well as stopping its spread following surgery, the companies said Wednesday.
- Independent data monitors said the cancer vaccine combined with Merck’s immunotherapy Keytruda showed “statistically significant and clinically meaningful improvements” over Keytruda alone at a pre-planned interim data check, permitting them to call the trial a success. The companies didn’t release detailed data but intend to do so at an upcoming medical meeting.
- Moderna’s share price more than doubled following the announcement. TD Cowen analyst Tyler Van Buren called it a “landmark moment,” and Jefferies analyst Andrew Tsai projected billions of dollars in sales from the vaccine in melanoma alone. The companies are also testing the treatment against lung, kidney and bladder cancer.
Dive Insight:
The promise of cancer vaccines training the immune system to detect and attack cancer cells has attracted billions of dollars into decades of research and development. Yet, that work has largely been unsuccessful. Cancer experts have chalked that failure up to past vaccines’ focus on a single antigen, or mutated protein, on cancer cells, as well as using them on people who are too sick for their bodies to fight off the disease or cancer cells’ own immunosuppressive properties.
Moderna, which rose to prominence on its COVID-19 vaccine, had focused heavily on its cancer immunotherapy pipeline before a pandemic that changed its fortunes. Now that work appears to be bearing fruit, as the Massachusetts biotechnology company appears to have learned from past setbacks in its development of intismeran autogene, which has also been known as V940 or MRNA-4157.
Intismeran is referred to as an “individualized antigen therapy,” having the ability through mRNA technology to detect up to 34 neoantigens on patients’ tumor cells, tailored to their disease as profiled through biological testing. The clinical strategy has been to focus on the adjuvant setting, which is when patients receive additional therapy to stave off disease return following a primary treatment like surgery.
In that key trial, titled INTerpath-001, enrollees were given intismeran plus Keytruda or Keytruda alone following surgical removal of their tumors. Investigators enrolled 1,137 people, and two-thirds were randomized to receive the intismeran-Keytruda combination.
In a Phase 2 trial of 157 people, the intismeran combination reduced the relative risk of death or recurrence by 44% over Keytruda alone. Keytruda by itself reduces the risk of death or recurrence by 43% when compared to a placebo, according to the results of a study known as KEYNOTE-054.
In client notes, analysts said Moderna executives would view a 20% risk reduction as a “clinical benchmark,” although Evercore ISI analyst Cory Kasimov wrote that anything below 25% would likely be viewed as “underwhelming.” Kasimov views a 35% to 40% reduction as “clearly differentiated.”
While intismeran could achieve blockbuster sales on the melanoma setting alone, a clearer view of its commercial promise should emerge based on results in kidney cancer — expected later this year or early next — along with bladder and non-small cell lung cancers. Those cancer types have better targets for immune-based therapies because they are so-called “hot” tumors, in which immune cells have infiltrated and can be activated.
