SCLC Treatment Gets a Boost as PharmaMar’s Lurbinectedin Bags Priority Review Status
By Ruchi Jhonsa, Ph.D.
The FDA has accepted PharmaMar and Jazz Pharmaceuticals’ request to process the new drug application (NDA) for Lurbinectedin on priority review. If approved, Lurbinectedin will be used for the second-line treatment of Small Cell Lung Cancer (SCLC). More importantly, it will be the first drug to be approved in 20 years that can treat SCLC in relapsed patients. The agency has set the Prescription Drug User Fee Act (PFUDA) target action date as August 16th of this year.
PharmaMar submitted the priority review application to the FDA on the basis of successful Phase II, monotherapy trials. Following the positive results in the trial, late last year, Jazz pharmaceuticals had struck a deal with PharmaMar, according to which the former would become the exclusive license holder of Lurbinectedin with US marketing rights following FDA approval.
Small Cell Lung Cancer
SCLC is an aggressive cancer of the lungs, which is characterized by a short doubling time, high growth fraction, and widespread metastases. SCLC forms 20% of all lung cancers and is highly responsive to chemo and radiation therapy. However, the relapse rate for this cancer after first-line treatment is high, with only 6% of patients surviving five years from diagnosis. Currently, there are no major improvements in the treatments of SCLC. Four years after the introduction of platinum etoposide doublet, the treatment options for SCLC remain unchanged. While immunotherapy drugs like Keytruda and Opdivo have been approved for the third line of treatment, there are no options available for the second line of treatment at the moment.
Lurbinectedin – Mode of Action
At the molecular level, SCLC is characterized by increased RNA polymerase activity, which causes excessive transcription in tumor cells. Lurbinectedin is a synthetic drug that binds to DNA minor groove and inhibits RNA polymerase II, causing a decrease in tumor cell proliferation primarily by inhibiting mitosis. Along with its activity in tumor cells, the drug also inhibits oncogenic transcription in tumor-associated macrophages, downregulating the production of cytokines that are essential for the growth of the tumor.
Phase II Monotherapy Basket Trial
The Phase II trial was a single-arm, multi-country trial, involving 105 patients from 39 centers in Europe and the USA that investigated the safety and efficacy of Lurbinectedin. Several important parameters like overall response rate, overall survival, the median duration of response, median progression-free survival were determined in the study. The trial met its primary endpoint of overall response rate (35.2%), which is way better than the FDA label data for Topotecan, the last molecule approved for second-line of treatment, in 1996. The noteworthy aspect is the activity demonstrated by Lurbinectedin in patients who have suffered a relapse within three months from the time of primary treatment. An overall response rate of 22.2% was observed in these patients when treated with the drug. The results were presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) in June 2019.
Approval of this drug will bring hopes to several patients suffering from recurring SCLC. “Lurbinectedin is showing to be a new potential treatment alternative for second-line small cell lung cancer, where, until now, no progress has been made for than two decades.” said Dr. Luis Paz-Ares, MD, Ph.D., of Hospital Universitario Doce de Octubre, while presenting the data at ASCO.
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