The U.S. Food and Drug Administration (FDA) accepted an application from PharmaMar and Jazz Pharmaceuticals asking for the accelerated approval of lurbinectedin to treat patients with small cell lung cancer (SCLC) whose disease progresses following platinum-based chemotherapy.
The new drug application (NDA) received priority review status, meaning the FDA will review and take action within a shorter period of time (six months) than is standard (10 months). The companies said they expect a decision by Aug. 16.
If approved, lurbinectedin will be the first new treatment for relapsed SCLC in more than 20 years, after the chemotherapy agent topotecan, approved by the FDA in 1996.
Lurbinectedin is an investigational therapy that inhibits RNA polymerase, a specialized protein essential to protein production that is overactive in many tumors. Lurbinectedin is designed to prevent cancer cells from making proteins they need to survive, and to stop the secretion of pro-tumoral molecules by certain immune cells, eventually killing cancer cells.
The treatment has received orphan drug status by authorities in the U.S., Europe, Switzerland, and more recently in Australia, The designation is intended to facilitate the development and review of new therapies for the treatment of rare diseases. In the U.S., this designation provides incentives to developers, including seven years of marketing exclusivity and a waiver from the FDA’s prescription fees.
The filing, submitted in December 2019, was supported by data from a multicenter, open-label Phase 2 trial (NCT02454972), showing that second-line treatment with lurbinectedin leads to high response rates in people with SCLC.
The trial included 105 patients with relapsed SCLC who had received prior platinum-based disease. Of them, 47 had platinum-resistant cancers, defined as time to relapse less than 90 days, and 58 had chemo-sensitive disease – 90 or more days from chemo to relapse.
The main goal was to determine if more than 30% of patients experienced a significant reduction in tumor burden — termed overall response rate — while receiving treatment with lurbinectedin. Secondary goals included overall survival and time patients lived without signs of disease worsening, termed progression-free survival (PFS).
In the trial, 35.2% of patients responded to lurbinectedin, meeting its primary endpoint. Results were even better in patients with platinum-sensitive disease, 45% of whom experienced a reduction in tumor burden. For those with platinum-resistant disease, 22.2% responded to treatment.
The proportion of patients achieving at least stable disease was better in the platinum-sensitive population (81.7%) than in the overall population (68.6%) and in those with platinum-resistant SCLC (51.1%).
In the overall population, responses lasted a median of 5.3 months, the median overall survival was 3.9 months, and patients remained alive and without signs of disease progression for a median of 9.3 months. Again, all measures were better in patients whose disease was sensitive to platinum-based chemo.
Lurbinectedin had a favorable and manageable safety profile, with the most common treatment-related adverse events being neutropenia, or low neutrophil levels, nausea or vomiting, and fatigue.
In January 2020, PharmaMar and Jazz signed an exclusive license agreement, under which Jazz holds lurbinectedin’s commercialization rights in the U.S.
The FDA’s accelerated approvals program targets new treatments intended for serious conditions and for filling an unmet medical need. During its review, the treatment’s therapeutic effects are measured using a surrogate endpoint — such as response rate — that is not a direct measure of clinical benefit but is thought to be a good predictor of it. Using a surrogate endpoint can shorten the time the FDA takes to approve a therapy.
After a treatment is first approved, companies are still required to conduct additional studies to confirm its clinical benefits. Once those are confirmed, the FDA then grants standard approval to the therapy.
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