FDA Action Alert: Biofrontera, BMS and Zealand

 

One upcoming decision—on a perioperative PD-1 regimen for lung cancer—comes as the FDA considers an overhaul of trial designs in this treatment setting.

The FDA is kicking off October with a trio of decisions on new drug candidates, including a rare disease medicine and a lung cancer treatment.

Read below for more.

Biofrontera Seeks Greater Maximum Dose for Actinic Keratosis Cream

By October 4, the FDA is set to release its decision on Biofrontera’s supplemental New Drug Application (sNDA) seeking to increase the maximum dose of its actinic keratosis gel Ameluz (aminolevulinic acid HCI) to up to three tubes per treatment.

Affecting more than 58 million people across the U.S., actinic keratosis is the most common precancerous skin lesion, according to Biofrontera. It is typically caused by prolonged exposure to the sun and manifests as rough bumps on the skin, especially on the face and arms. If left unchecked, actinic keratosis can develop into a potentially deadly type of skin cancer called squamous cell carcinoma.

Ameluz is a topical treatment that is administered by a healthcare provider alongside photodynamic therapy with a BF-RhodoLED lamp, which targets lesions with red light to activate Ameluz’s main therapeutic ingredient. People whose lesions have not completely resolved within three months after the initial treatment can undergo retreatment, according to the drug’s label.

Biofrontera’s sNDA proposes to use up to three tubes of Ameluz for the field treatment of actinic keratosis. If approved, this dosing adjustment could allow doctors to address large surface areas in one visit, making treatment more convenient for patients, according to the company.

The application is backed by data from two Phase I trials demonstrating the safety of three Ameluz tubes. Results showed that blood levels of Ameluz’s active ingredient and subsequent metabolites are transiently higher after the administration but were still far below the thresholds at which side effects occur. Systemic toxicities were comparable to one tube of Ameluz.

BMS Proposes Perioperative Opdivo Regimen in NSCLC

Bristol Myers Squibb is advancing Opdivo (nivolumab) for the perioperative treatment of resectable non-small cell lung cancer (NSCLC), including neoadjuvant PD-1 treatment plus chemotherapy followed by postoperative adjuvant Opdivo. The FDA’s decision is due by October 8.

The application is backed by data from the Phase III CheckMate -77T study, which showed significantly better event-free survival in patients treated with the perioperative Opdivo regimen. BMS published data from the study in October 2023, touting a 42% drop in the risk of disease recurrence, progression or death.

Participants in the Opdivo arm also achieved superior pathologic complete response and major pathologic response rates.

BMS’ application comes as the FDA rethinks its position on perioperative PD-1 treatment in lung cancer. In July 2024, the regulator’s Oncologic Drugs Advisory Committee unanimously backed the need for changes in perioperative trial designs, particularly to better differentiate the therapeutic contributions of different phases of treatment.

David Mitchell, president of the nonprofit Patients for Affordable Drugs, said during the adcomm meeting that patients and doctors need to know “which phase of treatment is contributing what.” Exposing patients to a year or so of adjuvant therapy without being sure of its therapeutic benefit “is not acceptable,” Mitchell said.

Zealand Awaits Verdict for Rare Disease Therapy

Also on or before October 8, the FDA is expected to release its decision on Zealand Pharma’s NDA for dasiglucagon, which the Danish biotech is proposing as a treatment for congenital hyperinsulinism (CHI).

Afflicting one out of 50,000 children, CHI is an ultrarare genetic disease characterized by dysfunctional pancreatic beta cells, which pump out too much insulin into the bloodstream. People with this condition suffer from frequent, recurrent and severe hypoglycemic episodes, which, if left unchecked, can lead to seizures, brain damage and even death.

Dasiglucagon is an investigational glucagon receptor agonist that promotes the secretion of stored sugar from the liver, helping counteract the glucose-lowering action of insulin. Zealand is developing the drug candidate as a subcutaneous continuous infusion delivered via a wearable pump system. Phase III data for dasiglucagon, released in May 2022, showed that the drug can significantly cut the need for intravenous glucose by 55% versus placebo.

Dasiglucagon previously won the FDA’s approval in May 2021 for the treatment of severe hypoglycemia in people with diabetes. The drug is marketed under the brand name Zegalogue for this indication.

Zealand’s CHI NDA for dasiglucagon will be reviewed by the FDA in two parts “to ensure the most efficient regulatory process,” the biotech noted in an August 2023 press release. The target action date on October 8 is for the first part, which covers dosing for up to three weeks. The second part of dasiglucagon’s NDA is for use beyond three weeks. The company expects to submit an application for this part by the end of 2024.

https://www.biospace.com/fda/fda-action-alert-biofrontera-bms-and-zealand