It’s almost an unspoken rule in the biopharma industry that companies seldom compare two drugs with similar mechanisms of action side by side in the same study. But Bayer decided to go ahead with a comparison of its “tumor agnostic” cancer drug Vitrakvi, though indirectly.
In cancers harboring an NTRK gene fusion, Bayer’s Vitrakvi could help patients live significantly longer than Roche’s Rozlytrek could, the German pharma unveiled at the European Society for Medical Oncology annual meeting. Both drugs have accelerated approvals to treat NTRK solid tumors regardless of their location in the body.
Rather than a head-to-head clinical trial, the conclusion came from a so-called matching-adjusted indirect comparison (MAIC). An MAIC analysis improves upon regular cross-trial comparisons—for example, comparing Vitrakvi’s trial data to Rozlytrek’s—by matching trial patients’ data based on baseline characteristics.
For the current study, researchers pooled data from three Vitrakvi trials—LOXO-TRK-14001, SCOUT and NAVIGATE—using a cutoff date in July 2020, and compared them with published aggregate data for three Rozlytrek trials—ALKA-372-001, STARTRK-1 and STARTRK-2—with an October 2018 cutoff date.
The researchers considered myriad factors when matching patients, including gender, age, race, tumor types, NTRK gene subtypes, ECOG body function performance score, number of prior lines of therapy, metastasis status and brain metastases. Altogether, 117 Vitrakvi patients and 74 Rozlytrek takers were included for efficacy analysis.
Vitrakvi reduced the risk of death by 57% versus Rozlytrek, the study found. Patients on Rozlytrek lived a median 23.9 months after a median 14.2 months of follow-up, while Vitrakvi still hasn’t reached the survival midpoint after 16.9 months of median follow-up. Vitrakvi also showed improvement on cancer progression, though the number wasn’t statistically significant.
Both drugs showed similar ability to shrink tumors, as Vitrakvi spurred a response in 67.3% of patients, compared with 53.6% for Rozlytrek. But significantly more patients experienced no sign of cancer while on the Bayer drug; complete response rate for Vitrakvi was 20.3%, versus 6.8% for Vitrakvi. At 32.5 months, Vitrakvi’s response also lasted longer than Rozlytrek’s 12.9 months.
For safety outcomes, which included different patients, the researchers said they were “comparable and low” for both drugs.
In a statement to Fierce Pharma, Roche’s Genentech pointed out the Bayer study is a retrospective analysis based on a small sample of patients. “There are currently no head-to-head, prospective studies of Rozlytrek and Vitrakvi, which is the gold-standard for comparing two therapies, given the significant limitations to cross-trial comparisons,” Genentech said.
The Roche subsidiary also highlighted Rozlytrek’s responses in tumors that have spread to the brain; industry watchers have argued that Rozlytrek is a better option than Vitrakvi in patients with brain metastases given the Roche drug’s ability to cross the blood-brain barrier.
Drugmakers seldom turn to head-to-head trials for meds in the same drug class, especially when it’s not required to win a regulatory go-ahead. These studies are costly and can be risky for showing a statistically significant advantage. In Vitrakvi and Rozlytrek’s case, Bayer argues that a head-to-head randomized control trial isn’t possible given TRK fusion cancer is rare.
Bayer sure is motivated to show Vitrakvi is a better drug than Rozlytrek. When Rozlytrek gained its FDA green light in August 2019, about a year after Vitrakvi, Roche priced it at $17,050 per month, which marked a hefty discount from Bayer’s list price of $32,800 per month, Evercore ISI analyst Umer Raffat pointed out in a note at the time.
With an additional indication for ROS1-positive non-small cell lung cancer, Rozlytrek brought in sales of 22 million Swiss francs ($24 million) in the first half of 2021. In a note last week, Jefferies analyst Peter Welford projected peak Rozlytrek sales of $475 million.
Bayer doesn’t report Vitrakvi sales separately. In a January note about another drug, RBC Capital Markets analyst Brian Abrahams described $750 million in peak sales as at “a similar magnitude” to Wall Street’s estimates for Vitrakvi.