Spectrum Pharma’s Rolontis Denied in Neutropenia Due to Manufacturing Issues
The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Henderson, Nev.-based Spectrum Pharmaceuticals. At issue was the company’s Biologics License Application (BLA) for Rolontis (eflapegrastim), which is being developed to treat neutropenia in patients receiving myelosuppressive anti-cancer drugs.
Neutropenia is low white blood counts, specifically neutrophils, in the blood, caused by certain types of chemotherapy drugs. The rejection does not appear to be related to clinical deficiencies, but associated with manufacturing, indicating another inspection will be necessary.
The drug is a novel, long-acting granulocyte colony-stimulating factor (G-CSF). The BLA was based on data from two identical Phase III trials, ADVANCE and RECOVER, which studied the drug in 643 early-stage breast cancer patients. In both trials, the drug showed non-inferiority in duration of severe neutropenia and had a safety profile similar to chemotherapy drug pegfilgrastim.
In October 2020, Spectrum reported that the FDA required an inspection of the Hanmi Bio Plant in South Korea before it could approve the BLA. The agency could not conduct the inspection during the review cycle because of travel-related restrictions from the COVID-19 pandemic.
Then, on March 16, 2021, the company announced the FDA had scheduled the pre-approval inspection at the for May 2021.
“I am thrilled that the FDA informed us that they will be conducting a pre-approval inspection of the Rolontis manufacturing facility in May,” said Joe Turgeon, president and chief executive of Spectrum Pharmaceuticals. “We believe the pre-approval inspection marks the final step in the Rolontis review process.”
Then on June 1, Spectrum reported the FDA was onsite for their inspection.
The company indicated they plan to meet with the FDA to determine the next course of action.
Meanwhile, the company appears focused on another pipeline drug, poziotinib. In June, it presented data on poziotinib CNS activity in patients with non-small cell lung cancer (NSCLC) with EGFR or HER2 exon 20 mutation. CNS metastases are common complications of metastatic disease in NSCLC patients and can be life-threatening. The data showed clinically meaningful CNS activity for the drug in these patients. It was based on data from the ZENITH20 clinical trial and presented results for 284 patients from Cohorts 1, 2 and 3. Of them, 36 patients had brain metastases.
At the company’s first-quarter financial report on May 13, 2021, Turgeon said, “Our top priority is the submission of the NDA to the FDA for posiotinib based on the positive data from Cohort 2 of the ZENITH20 clinical trial. The additional data on twice-daily dosing presented at AACR has the potential to significantly expand the value of poziotinib. We also look forward to the pre-approval inspection of the Rolontis manufacturing facility which has been scheduled for later this month.”
The NDA is for poziotinib in patients with previously treated locally advanced or metastatic NSCLC with HER2 exon 20 insertion mutations.
The company’s second-quarter financial report is scheduled for August 12. At the first-quarter report, the company recorded a net loss of $35.7 million, or $0.25 loss per basic and diluted share, for the first quarter. It ended the quarter with $162.9 million in cash, cash equivalents, and marketable securities. It reported a non-GAAP net loss of $29.4 million.
Shares fell almost 30% Friday at the news of the FDA rejection.