Let the Rain fall down: Biotech's shares tumble 80% as lone asset fails to improve survival in liposarcoma

Storm clouds are brewing for Rain Oncology after its lead asset failed to improve progression-free survival (PFS) versus chemotherapy in a phase 3 trial of patients with liposarcoma.

Rain’s shares tumbled more than 80% Monday morning from a prior close of $9.93 to $1.62 as the biotech announced that development in dedifferentiated liposarcoma would stop. Milademetan is an oral, small-molecule drug Rain snagged from Daiichi Sankyo in 2020. Besides liposarcoma, the therapy is in development for an array of solid tumor indications, although those trials are earlier in development.

In the phase 3 MANTRA study, milademetan failed on the primary endpoint of advancing PFS when compared to Janssen Pharmaceuticals’ Yondelis. Milademetan achieved a PFS of 3.6 months while the standard of care chemotherapy was 2.2 months.

“We are very disappointed in the outcome of the Mantra trial, as the results did not closely mirror prior clinical results in patients with DD LPS,” said Rain CEO Avanish Vellanki. “We are truly saddened we will not likely be able to offer patients new treatment options for this challenging disease. However, the quality and robustness of the global Mantra trial reflects an unambiguous data set.”

As for safety, the most common treatment-emergent adverse events in the milademetan arm were thrombocytopenia (low platelet count), neutropenia (low white blood cell count) and anemia. Patients in this group had a dose reduction rate of 44% compared to 29% in the Yondelis arm. Discontinuations for Rain’s therapy were lower at 12% compared to 19% for the chemotherapy.

Rain will now walk away from the liposarcoma indication and “re-evaluate the path forward for milademetan,” according to Vellanki.

Co-founded by Vellanki and Robert Doebele, M.D., Ph.D., Rain set out to push milademetan, an inhibitor of the MDM2 gene that drives many cancers. The target has been around for a long time but has so far eluded drugmakers—including the likes of Amgen, Merck, Novartis, Roche and Sanofi.

Rain thought that milademetan could finally crack the code, as Daiichi Sankyo had developed the therapy with an intermittent dosing schedule to avoid side effect concerns.

A week and a half ago, Rain presented first-quarter earnings, touting the development program for milademetan and expressing excitement in the pending readout. The company reported $110 million in cash runway as of the end of the first quarter, which was expected to fund all ongoing and planned clinical trials for the therapy. A phase 1/2 study of milademetan in combination with Roche’s Tecentriq was expected to kick off this year.