Dive Brief:

• FDA has approved Novocure's tumor treating fields delivery system NovoTTF-100L for use in patients with malignant pleural mesothelioma (MPM).

• The approval under the Humanitarian Device Exemption (HDE) makes NovoTTF-100L the first new treatment cleared for use in MPM for 15 years, and moves Novocure into the treatment of cancer of the torso for the first time.

• The approval of NovoTTF-100L on the strength of an 80-subject, single-arm study drew criticism from oncologist and U.S. approval standards critic Vinay Prasad, who called it a "new low" for FDA.

Dive Insight:

The options available to physicians who treat the 3,000 patients diagnosed with MPM in the U.S. every year have remained unchanged for a long time. Pemetrexed plus cisplatin emerged as a preferred option for the treatment of patients with unresectable forms of the lung cancer following the release of clinical trial data linking the combination to overall survival of 12.1 months in 2003.

In an attempt to improve on that result, Novocure tested NovoTTF-100L for the indication. The device generates electric fields designed to disrupt the division of solid tumor cells, leading to the control or shrinkage of cancers.

Novocure's program centered on an 80-person clinical trial, the data from which persuaded FDA to approve the device under its rare disease pathway, HDE. The study posted an overall survival of 18.2 months in people who received NovoTTF-100L plus a pemetrexed-based chemotherapy regimen. The figure compares favorably to the 12.1 months achieved in the pemetrexed-cisplatin trial.

However, while the data suggest NovoTTF-100L is better than pemetrexed plus cisplatin alone, the lack of a control arm in the study raises questions.  Comparisons of data from different sources are confounded by multiple factors that make it hard to draw concrete conclusions.

The lack of a control arm in the Novocure trial means NovoTTF-100L may have faced an inaccurately easy comparison to standard-of-care chemotherapy. That worry was articulated by Prasad, a hematologist-oncologist and associate professor of medicine at Oregon Health and Science University, who took to Twitter to call the authorization of NovoTTF-100L a "new low" for FDA.

Novocure, in contrast, called the approval a "major milestone" for the company. The company won approval for its second-generation tumor treating field technology in glioblastoma in 2016 but has seen sales constrained by a Medicare non-coverage policy. Medicare is planning to relax its position but will limit coverage to a narrow set of criteria.

There are particular challenges with MPM. Writing in JAMA Oncology in 2017, physicians argued that the heterogeneity in prognosis of MPM means "a control arm is needed to correctly interpret the outcome of patients treated." To support their case, the physicians cited a trial of Roche drug Avastin that achieved an overall survival of 15.6 months. In a single arm trial, that result would have looked promising. Yet, the trial failed as the control arm recorded an overall survival of 14.7 months.

Gaining approval in MPM gives Novocure another avenue for growth but, in the near term, it will be constrained by the sort of reimbursement restrictions that held back its early efforts to grow sales in glioblastoma. Novocure plans to hire five mesothelioma territory managers to drive growth but expects reimbursement claims to go through an appeal process in the early launch phase.