Rolontis review: Spectrum confident manufacturing deficiencies resolved

Spectrum Pharmaceuticals has resubmitted the BLA for eflapegrastim following the remediation of manufacturing deficiencies at a drug substance facility in Korea.

In August 2021, Spectrum received a complete response letter (CRL) from the US Food and Drug Administration (FDA) for its long-acting granulocyte-colony stimulating factor (G-CSF) agent Rolontis (eflapegrastim).

The letter, which put a hold on Spectrum’s Biologics License Application (BLA) for eflapegrastim, identified manufacturing challenges.

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But during his firm’s fourth quarter 2021 financial call last week, CEO Tom Riga said remediation of manufacturing deficiencies has occurred and the BLA has been resubmitted to the FDA for review.

“The CRL focused really on two things: It identified manufacturing challenges, both at the drug product facility and the drug substance facility,” he told stakeholders. “Subsequently, we had a Type A meeting with the FDA where the issue at the drug product facility – which had nothing to do with Rolontis – was cleared and was not a gating item to resubmission. So really, the sole challenge from the CRL was the remediation efforts at the drug substance facility in Korea.”

Eflapegrastim is being developed for the treatment of chemotherapy-induced neutropenia. It comprises two protein components, an analog of G-CSF and an Fc antibody fragment, tethered by a flexible polyethylene-glycol linker. It was developed by Korean drugmaker Hanmi Pharmaceutical and is licensed to Spectrum as part of a long-term partnership between the two companies. The molecule is manufactured by Hanmi at its biomanufacturing site in South Korea, which offers 4 x 10,000 L bioreactor tanks across two buildings.

“We have worked very closely with our partner on the remediation and capital plan that resulted from that initial inspection and ultimately announced today that we resubmitted. So a Class 2 resubmission is what I was articulating at a 30-day acceptance and a 6-month clock. So that date will put you around September [for an approval decision].”

However, Riga said the decision would be dependent on the regulators reinspecting the Korean facility.

“Now will there be challenges with them traveling to Korea given the COVID realities of what we had in the past? I don’t have a crystal ball, but I do know that the FDA is conducting international inspections today. We don’t see it as a barrier today, but we’re going to keep an eye on it, and we’re looking forward to them scheduling that date and getting to Korea to conduct the inspection.”