Bristol Myers' $4.1B Turning Point buy yields FDA approval for lung cancer drug Augtyro

Watch out, Pfizer and Roche. Thanks to an acquisition and now an FDA approval, Bristol Myers Squibb is entering a niche lung cancer market.

The FDA has cleared Bristol Myers’ repotrectinib, to be branded as Augtyro, to treat non-small cell lung cancer (NSCLC) patients whose tumors have ROS1 oncogenic fusions. The New Jersey pharma company said it plans to make the drug available starting in mid-December.

BMS got Augtyro through its $4.1 billion acquisition of Turning Point Therapeutics last year. And Wednesday’s approval gives BMS an opportunity to challenge Pfizer’s Xalkori and Roche’s Rozlytrek in ROS1-positive NSCLC, which accounts for about 1% to 2% of all NSCLC cases.

Augtyro could reach $1.4 billion sales at peak in the first-line setting and $455 million in the second line, Leerink Partners analysts predicted at the time of the Turning Point deal.

Clinical trial data suggest Augtyro has the potential to become a new standard-of-care option for this NSCLC subtype, Jessica Lin, M.D., of the Massachusetts General Hospital, said in a statement Wednesday.

Lin was the primary investigator of BMS’ TRIDENT-1 trial. In that single-arm phase 1/2 trial, Augtyro shrank tumors in 79% of patients who had not received a tyrosine kinase inhibitor (TKI) like Augtyro, with the response lasting a median 34.1 months.

Among those pretreated with one ROS1 agent but not chemotherapy, the overall response rate was 38%, lasting a median 14.8 months.

The drug also showed an ability to contain tumors that had spread to the brain. Investigators observed responses in the brain in seven of eight TKI-naïve patients with measurable central nervous system metastases, and in five of 12 TKI-experienced patients.

ROS1-positive NSCLC is one of the few cancer indications where tumor shrinkage data have been enough to support full FDA approvals. Pfizer’s Xalkori became the first TKI greenlighted for this use based on an objective response rate in 66% of 60 patients enrolled in a phase 1 trial. The median duration of response was 18.3 months.

Roche’s Rozlytrek entered the ring in 2019, armed with a trial tumor response rate of 78% among 51 patients. The responses continued for at least a year for 55% of patients.

Before Augtyro’s approval, Xalkori has been the treatment of choice for advanced ROS1-positive NSCLC without CNS metastases, while Rozlytrek is the preferred option for those with CNS metastases, according to a 2020 JCO Oncology Practice article authored by two Mayo Clinic doctors.

Despite boasting an additional indication to treat NTRK gene fusion-positive solid tumors, Rozlytrek only ginned up 63 million Swiss francs in sales ($71 million) in the first nine months of 2023. BMS is also testing Augtyro in a phase 2 NTRK pan-tumor trial.

Pfizer’s Xalkori is also allowed to treat ALK-positive NSCLC, but thanks partly to Pfizer’s next-generation Lorbrena, the older TKI saw sales drop 27% year over year to $86 million during the first three quarters of the year.

Given the low level of sales from those earlier drugs, it might be hard to imagine a blockbuster market potential for Augtyro. And Leerink analysts back in June 2022 acknowledged that many investors didn’t share their optimism. 

Augtyro has demonstrated the best tumor response data among the three agents, and it holds another advantage over the competitors.

One problem with Pfizer’s and Roche’s offerings is that they couldn’t overcome a common resistance mutation in ROS1-positive NSCLC called G2032R. By comparison, Augtyro appeared to be able to tackle G2032R, which accounts for 41% of resistance mutations in ROS1-positive NSCLC.

On the safety side, Augtyro’s side-effect profile looks largely in line with its two competitors, William Blair analysts said in a Thursday note. But along with the strong CNS activity comes with a high rate of dizziness in Augtyro’s study, a point that the analysts said they will continue to monitor. Some cases were serious enough to require dose interruption or reduction, the team noted. 

Augtyro’s label does not include warnings for QT prolongation, as is the case with Xalkori and Rozlytrek. The William Blair team is encouraged by this differentiator “given the burden of monitoring and serious cardiac consequence associated with prolongation.” 

All considered, William Blair has maintained its estimates for Augtyro sales to reach $258 million by 2027, which also assumes an approval in Europe next year.

BMS has found itself in a tough spot lately, where top-selling drugs and key launches have been disappointing investors. That’s why the company is turning to dealmaking again, having agreed to buy KRAS drugmaker Mirati Therapeutics for $5.8 billion.