AZ drops midstage cancer drug vistusertib

AstraZeneca R&D, Boston, USA
Vistusertib was in multiple phase 2 trials as a monotherapy and in combination with other drugs. (AstraZeneca)

AstraZeneca has decided to discontinue one of its midstage cancer drugs—mTOR inhibitor vistusertib—despite reporting encouraging clinical data earlier in the year.

The company’s third-quarter results update indicates (PDF) vistusertib has been discontinued both as a monotherapy in solid tumors and in combination with Calquence (acalabrutinib), AZ’s recently-approved BTK inhibitor, for blood cancers.

AZ’s chief medical officer Sean Bohen M.D., Ph.D., wouldn’t comment on the specific reasons for the decision on a call with reporters this morning but suggested it came about as a result of re-prioritization of the R&D portfolio.

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“We’re in the fortunate position of having to choose between different programs within a very rich pipeline,” he said. “We have several factors to consider in making these choices, [including] the tolerability and efficacy, but also the evolution of treatment within a disease area.”

In its updated pipeline this morning, AZ said the: “Reason for discontinuation: safety/efficacy,” but that’s all she wrote.

AZ had advanced vistusertib (formerly AZD2014) into about 10 phase 2 trials across a broad range of cancers, including ovarian, breast and lung cancers and B cell malignancies, although it had previously been dropped in renal cancer. The studies were testing the drug on its own as well as alongside Calquence and other AZ drugs including PD-L1 inhibitor Imfinzi (durvalumab), PARP inhibitor Lynparza (olaparib) and experimental FGF tyrosine kinase inhibitor AZD4547.

In August, the Institute of Cancer Research in the U.K. reported what it described as “exciting” phase 1 results in ovarian and lung cancers when vistusertib was combined with paclitaxel chemotherapy, causing tumors in more than half of patients with ovarian cancer and over a third with lung cancer to shrink, and stopped patients’ cancers from growing for nearly six months.

“There has been great progress in the treatment of ovarian and lung cancer, so in that respect the bar also moves over time,” commented Bohen on the call. “We will be able to provide more information in the future.”

The mTOR pathway is already fairly well-covered by approved drugs, notably Pfizer’s Torisel (temsirolimus) and Novartis’ Afinitor (everolimus), and with upward of two dozen newer inhibitors in the clinical pipeline—plus a raft of candidates that target both mTOR and other pathway components such as PI3K/ACT—it looks like AZ has ducked out of an increasingly crowded field.