FDA Action Alert: Zosano, Spectrum, Regeneron, Kala and Merck

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The U.S. Food and Drug Administration (FDA) has several PDUFA dates for the rest of October, although two of them were already approved. Here’s a look.

Zosano Pharma’s Qtrypta for Migraine

Zosano Pharma, based in Fremont, California, has a target action date of October 20, 2020 for its transdermal microneedle product candidate, Qtrypta, for acute treatment of migraine. Qtripta is the company’s investigational formulation of zolmitriptan delivered using its transdermal needle system. The system is made up of titanium microneedles coated with a drug, in this case zolmitriptan. The microneedles can penetrate the stratum corneum, where the drug dissolves and easily enters the bloodstream.

On September 30, the company received a discipline review letter (DRL) from the FDA related to the 505(b)(2) New Drug Application (NDA) for Qtrypta. These types of letters are used to inform sponsor companies of preliminary comments on deficiencies seen during the review of the NDA in regard to a particular review discipline. The DRL mentioned two issues related to clinical pharmacology section of the NDA. The first was questions about unexpected high plasma concentrations of zolmitriptan seen in five study subjects from two pharmacokinetic studies and how the data affected the overall clinical pharmacology section of the application. The second was related to differences in zolmitriptan exposures seen between subjects who received different lots of Qtrypta in the clinical trials. Although not definite, the company indicated they did not expect approval at the PDUFA date of October 20.

“We are disappointed in this notification and are in the process of evaluating and addressing FDA’s comments,” said Steven Lo, president and chief executive of Zosano. “We believe Qtrypta represents an attractive therapeutic alternative for patients suffering from migraines and look forward to working with FDA through the NDA review process.”

Spectrum Pharmaceuticals’ Rolontis for Chemotherapy-Induced Neutropenia

Spectrum Pharmaceuticals, headquartered in Henderson, Nevada, has a target action date of October 24 for its Biologics License Application (BLA) for Rolontis (eflapegrastim) for chemotherapy-induced neutropenia. The BLA was built on data from two successful pivotal Phase III clinical trials, ADVANCE and RECOVER. They evaluated a total of 643 early-stage breast cancer patients for the treatment of neutropenia resulting from myelosuppressive chemotherapy. In both trials, the drug demonstrated non-inferiority in duration of severe neutropenia and a similar safety profile to pegfilgrastim.

“If approved, Rolontis could be the first novel granulocyte colony-stimulating factor (G-CSF) available to healthcare providers in over 15 years,” said Joe Turgen, president and chief executive officer of Spectrum in a December 26, 2019 statement. “We have confidence in the future of Rolontis and are looking forward to potentially competing in this multibillion-dollar market.”

Regeneron’s REGN-EB3 for Ebola

Regeneron Pharmaceuticals had a target action date of October 25 for its BLA for REGN-EB3, an investigational triple antibody cocktail for Ebola virus infection. As reported on October 15, the FDA approved the therapy under the name Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn). The cocktail was engineered using the company’s VelocImmune platform and associated VelociSuite technologies. The antibodies have similar structure, but bind to different, non-overlapping antigens on Zaire ebolavirus glycoprotein. They neutralize the virus by blocking its ability to invade patients’ bodies and by recruiting other immune cells to target infected cells.

“We are incredibly proud that the FDA has approved Inmazeb, which is also known as REGN-EB3,” said George D. Yancopoulos, president and chief scientific officer of Regeneron. “This is the first time the FDA has approved a treatment specifically for Ebola, which has caused a number of deadly outbreaks. Decades of investment in our VelociSuite rapid response technologies, the dedication of world-class scientists, and the courageous contributions of healthcare providers and patients, together with remarkable cooperation between leading international health organizations and govenrments, have led to this important moment.”

Kala Pharmaceuticals’ Eysuvis for Dry Eye Disease

Kala Pharmaceuticals, based in Watertown, Massachusetts, has a target action date of October 30 for its resubmitted NDA for Eysuvis (loteprednol etabonate ophthalmic suspension) 25% for short-term treatment of the signs and symptoms of dry eye disease. It was resubmitted in April 2020 in response to a Complete Response Letter (CRL) it received in August 2019. The CRL indicated that positive data from an additional trial was needed to support a resubmission. The resubmission was based on positive data from the previous trials of the drug as well as positive results from STRIDE 3. STRIDE 3 met both primary symptoms endpoints, demonstrating a statistically significant improvement in ocular discomfort severity in both the overall intent-to-treat (ITT) population and in a subgroup of ITT patients with more severe ocular discomfort at baseline.

During the company’s August 6 second-quarter financial update, Mark Iwicki, chairman, president and chief executive officer of Kala said, “In May, the FDA accepted our NDA resubmission for Eysuvis, bringing us closer to potentially delivering the first prescription medicine for the short-term treatment of dry eye disease, including dry eye flares, which affects approximately 33 million people in the United States. We have now turned our attention toward a potential U.S. launch before year-end. Given our established relationships with eye care professionals across the United States and our experience with Inveltys, we believe we are well-positioned for a successful launch of Eysuvis, if approved.”

Merck’s Keytruda for Adults with R/R Classical Hodgkin Lymphoma

Merck had a target action date of October 30 for its supplemental BLA for Keytruda, it’s blockbuster checkpoint inhibitor, as a monotherapy for adults with relapsed or refractory classical Hodgkin lymphoma (cHL). On October 15, the FDA approved the expanded label for Keytruda for this indication.

The sBLA was based on results from the pivotal Phase III KEYNOTE-204 trial. In that trial, Keytruda demonstrated significant improvement in progression-free survival (PFS) compared to brentuximab vedotin (BV), which is current standard of care in this patient population.

“Classical Hodgkin lymphoma accounts for more than nine in 10 cases of Hodgkin lymphoma, which impacts approximately 7,400 patients a year in the U.S.,” said Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories, in a July statement. “For patients with classical Hodgkin lymphoma who do not achieve remission after first-line treatment, there is a particularly poor prognosis due to the limited options available.”

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