In pleasant surprise for GSK, FDA approves Jakafi challenger Ojjaara in broad blood cancer use

For the JAK inhibitor momelotinib, which GSK obtained in its $1.9 billion acquisition of Sierra Oncology, a three-month delay at the FDA was worth the wait.

After a delay to review additional data, the FDA has approved GSK’s momelotinib, now branded Ojjaara, to treat intermediate- or high-risk myelofibrosis in patients with anemia. In a pleasant surprise for Ojjaara, the FDA approved the medicine for patients with the blood cancer regardless of their treatment history.

When GSK purchased Ojjaara’s developer Sierra last year, the company valued the biotech based on a potential second-line approval, GSK’s chief commercial officer, Luke Miels, said in an interview. With this broader-than-expected label, Ojjaara will be able to generate peak sales “comfortably above blockbuster status,” he said.

The broad FDA nod somewhat levels the playing field for Ojjaara against Incyte’s well-established Jakafi. But instead of launching an all-out challenge of Jakafi, GSK will only be able to target patients who are anemic.

Patients who are already anemic at diagnosis make up about half of the first-line population, according to Miels. In the second line, around 60% to 70% of patients are anemic. Jakafi might worsen anemia in some myelofibrosis patients.

Despite the surprisingly big indication, GSK will keep the U.S. Ojjaara marketing team at about 75 people, who Miels said are “adequately able to target the population. Ultimately, Ojjaara may reach “a sizable proportion” of myelofibrosis patients who are anemic at diagnosis, plus a second-line population of patients who become anemic either through the cancer itself or the activity of Jakafi, Miels said.

Ojjaara had a checkered past before GSK’s Sierra acquisition. In a phase 3 trial conducted by Ojjaara’s previous owner Gilead in JAK-naïve patients, Ojjaara failed to outperform Jakafi on a myelofibrosis symptom scorecard.

Sierra picked a different path. Rather than trying to show superiority over Jakafi in the first-line setting, the phase 3 MOMENTUM trial pitted Ojjaara against the synthetic steroid danazol in JAK-inhibitor-exposed patients with anemia. Compared with danazol, Ojjaara helped a significantly greater proportion of patients achieve at least a 50% reduction on the total symptom score after 24 weeks of treatment.

In a 48-week follow-up, the trial found that 97% of patients who responded to Ojjaara at week 24 remained in response, and that the drug also started to work in 29% of initial nonresponders.

In approving Ojjaara in the first line, the FDA also considered a subgroup analysis of the failed SIMPLIFY-1 trial in patients with anemia. There, Ojjaara had numerically lower spleen volume response rate compared with Jakafi.

Now, the FDA appears to think that Ojjaara doesn’t have to beat Jakafi to deserve a first-line nod. Miels said he views this as “a recognition there’s a very elegant mechanism at play.”

Specifically, JAK inhibition gives Ojjaara the ability to reduce the size of the spleen and address other symptoms for myelofibrosis patients. But an off-target mechanism against activin A receptor type I (ACVR1) could explain the drug’s additional benefits in controlling anemia.

“That’s really important in the context of myelofibrosis because anemia status and transfusion requirements frequency are directly correlated with life expectancy,” Miels noted.

Moving forward, GSK is exploring potential combinations, including with a BET inhibitor, Miels said. Without giving out more details, the commercial chief said GSK is also interested in other hematological indications such as myelodysplastic syndromes, where anemia is also problem.

GSK originally bought Ojjaara to complement its BCMA-targeted blood cancer drug Blenrep. But GSK late last year decided to withdraw Blenrep’s accelerated approval in late-line multiple myeloma after the drug failed in a confirmatory trial. And the Europea Medicines Agency’s human medicines committee just refused to renew Blenrep’s conditional authorization, which portends EU market withdrawal once the negative opionion is formally adopted by the European Commission.

The company still has two phase 3 trials for Blenrep combinations in second-line treatment, with readouts expected this year.

For its part, Incyte is trying to pair Jakafi with other agents as well. But the Delaware pharma hit a setback earlier this year when the FDA rejected an extended-release formulation, disrupting the company’s plan to introduce fixed-dose combinations.

In GSK’s broader burgeoning oncology portfolio, Jemperli in July snagged the PD-1/L1 class’ first FDA approval as a frontline treatment for endometrial cancer that’s mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).