Agios' Tibsovo has an FDA green light in AML. Why did European regulators turn it back?

Agios may have persuaded the FDA into doling out an approval for its acute myeloid leukemia (AML) drug Tibsovo based on phase 1 results, but it failed to convince European regulators to do the same thing.

Friday, Agios said it had withdrawn a European application for Tibsovo in relapsed or refractory IDH1-mutant AML. The decision came as the European Medicines Agency’s (EMA's) Committee for Medicinal Products for Human Use found that a small, single-arm phase 1 study—the foundation of Tibsovo's 2018 FDA nod—was not enough to support approval.

As a result, SVB Leerink’s Andrew Berens lowered his estimate for peak Tibsovo revenues in the EU to $159 million from $237 million, saying the setback reduces the “fundamental value” of the company’s IDH franchise.

The IDH inhibitor's remaining opportunity in Europe lies in previously untreated patients. While Agios doesn’t have a placebo-controlled late-stage trial planned in the relapsed or refractory patient group, the company is running two phase 3 trials in newly diagnosed AML patients.

The Agile trial pairs Tibsovo with Celgene’s Vidaza for patients ineligible for chemotherapy. The Hovon150 trial tests Tibsovo alongside chemo in those fit enough to handle the strong treatment. The company said it plans to file for approvals in both the U.S. and EU if those trials come up positive.

RELATED: Bristol Myers Squibb's targeted AML drug Idhifa fails to extend patients' lives

Drug reviewers at the EMA may have a point in refusing to approve Tibsovo based solely on the phase 1, which found Tibsovo cleared signs of cancer and fully restored blood counts in 32.8% of previously treated patients. Recently, Bristol Myers Squibb’s Idhifa—an IDH inhibitor FDA-approved to treat IDH2-mutated AML—failed to show it could extend lives in a phase 3 trial.

Agios might have known that an EMA refusal was coming. Last December, BMS also took back its European Idhifa application after similar feedback from the EMA. But Agios had argued that patients with IDH1 mutations have a worse prognosis than those with IDH2 abnormalities, and that running a randomized trial in relapsed or refractory IDH1 patients was not feasible, Berens noted.

Tibsovo is also approved in the U.S. as monotherapy for newly diagnosed AML patients not eligible for chemo. Agios is looking to file the drug in previously treated IDH1-mutant cholangiocarcinoma, a rare cancer of the bile ducts, after a phase 3 showed a significant, 63% reduction in the risk of disease progression and a trend in survival improvement. Besides Tibsovo, Agios is developing vorasidenib, a pan-IDH inhibitor, in a phase 3 trial.