Two months earlier than expected, Pharmamar SA and partner Jazz Pharmaceuticals plc received an accelerated FDA approval of Zepzelca (lurbinectedin) to treat relapsed metastatic small-cell lung cancer patients.
The approval potentially triggers a $250 million payment to Madrid-based Pharmamar based on its commercialization deal signed with Dublin-based Jazz last December. It also offers a new option for patients, having shown a 35% overall response rate (ORR). The historical ORR rate for the chemotherapy topotecan is 16.9%.
Zepzelca, an alkylating drug that binds guanine residues within DNA, will be used specifically for those adult patients with disease progression during or following platinum-based chemotherapy.
The NDA, filed in December, was based on a phase II trial, and continued approval may require results from a confirmatory study. The drug should be available to patients in the U.S. in early July, several weeks before Zepzelca’s Aug. 16 PDUFA date. Zepzelca received priority review in February.
The approval is based on the ORR of 35% and a median duration of response of 5.3 months, as measured by investigator assessment. An independent review committee found those results to be 30% and 5.1 months, respectively. The results came from a phase II monotherapy basket trial of 105 patients at 39 centers in eight Western European countries and the U.S.
Beyond platinum-based therapy, few treatment options exist for SCLC.
“While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment,” said Jazz Chairman and CEO Bruce Cozadd in a statement.
Pharmamar and Jazz partnered in December 2019, following the submission of the NDA, for U.S. commercialization rights in a deal worth $1 billion. A total of $200 million was paid up front, but the deal included another $800 million in milestone payments, including $250 million upon accelerated or full regulatory approval within certain timelines. The other $550 million in milestone payments are tied to commercial activity. Royalties range from the high teens up to 30%, and Pharmamar could receive additional payments on approval in other indications.
Zepzelca gained orphan drug designation for SCLC in August 2018. According to the American Cancer Society, about 10% to 15% of lung cancers in the U.S. are small-cell, and 30,000 new cases are recorded each year.
The drug, once known as PM-1183, will be administered intravenously in an outpatient clinic delivering a 3.2-mg/m2 dose over one hour, repeated every 21 days until disease progression or an unacceptable level of toxicity.
Clinical results show common adverse reactions are leukopenia, lymphopenia, fatigue, anemia and neutropenia, as well as gastrointestinal issues and pain. The drug was discontinued in 1.9% of patients participating in the phase II trial and was delayed in 30.5% of patients due to an adverse reaction.
Pricing was not immediately available.
Press announcements were released less than a half hour before market close on June 15. Still, Jazz shares (NASDAQ:JAZZ) climbed 5.56%, or $5.82, to close at $110.50, while Pharmamar’s stock (OTC:PHMMF) saw a spike of 10%, or 70 cents, to close at $7.65.