FDA Action Alert: Biofrontera, BMS and Zealand

The FDA begins October with three decisions on new drug candidates, including a rare disease drug and a lung cancer treatment.

Read below to find out more.

Biofrontera aims for higher maximum dose for actinic keratosis cream

The FDA will publish its results by October 4th Decision as part of Biofrontera's supplemental New Drug Application (sNDA), which aims to increase the maximum dose of its actinic keratosis gel Ameluz (aminolevulinic acid HCI) to up to three tubes per treatment.

According to Biofrontera, actinic keratosis is the most common precancerous skin lesion, affecting more than 58 million people in the United States. 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 fatal type of skin cancer called squamous cell carcinoma.

Ameluz is a topical treatment administered by a healthcare provider along with photodynamic therapy using a BF-RhodoLED lamp, which targets lesions with red light to activate Ameluz's main therapeutic active ingredient. People whose lesions have not completely cleared up within three months of the first treatment may undergo retreatment, according to the medication label.

Biofrontera's sNDA suggests using up to three tubes of Ameluz for the field treatment of actinic keratosis. If approved, this dosage adjustment could allow doctors to treat large surface areas in one visit, making treatment more comfortable for patients, the company said.

The application is supported by data from two Phase I studies demonstrating the safety of three Ameluz tubes. The results showed that blood levels of Ameluz's active ingredient and its subsequent metabolites were temporarily higher after administration, but were still well below the thresholds at which side effects occur. The systemic toxicities were comparable to those of a tube of Ameluz.

BMS suggests perioperative Opdivo regimen in NSCLC

Bristol Myers Squibb advances 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 Decision is due by October 8th.

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

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

BMS' application comes as the FDA is reconsidering its position on perioperative PD-1 treatment for lung cancer. In July 2024, the regulator's Oncology Medicines Advisory Committee met unanimously supported the need for changes in perioperative study designs, particularly to better differentiate the therapeutic contributions of different treatment phases.

David Mitchell, president of the nonprofit Patients for Affordable Drugs, said during the Adcomm session that patients and physicians need to know “which phase of treatment contributes what.” It is “not acceptable” to subject patients to adjuvant therapy for a year without being sure of the therapeutic benefit, Mitchell said.

Zealand awaits ruling on treatment for rare diseases

The FDA is also expected to release its findings on or before October 8th Decision on Zealand Pharma's NDA for dasiglucagon, which the Danish biotech company proposes to treat congenital hyperinsulinism (CHI).

Affecting one in 50,000 children, CHI is an extremely rare genetic disorder characterized by dysfunctional pancreatic beta cells that pump too much insulin into the bloodstream. People with this condition experience frequent, recurrent, and severe hypoglycemic episodes that, if left untreated, can lead to seizures, brain damage, and even death.

Dasiglucagon is a glucagon receptor agonist in development that promotes the secretion of stored sugar from the liver, counteracting the glucose-lowering effects of insulin. Zealand is developing the drug candidate as a continuous subcutaneous infusion delivered via a portable pump system. Phase III data for dasiglucagon published in May 2022 showed that the drug can do this significantly reduce the need for intravenous glucose by 55% compared to placebo.

Dasiglucagon previously received FDA approval in May 2021 to treat severe hypoglycemia in people with diabetes. The drug is marketed for this indication under the brand name Zegalogue.

New Zealand's CHI NDA for dasiglucagon will be reviewed by the FDA in two parts “to ensure the most efficient regulatory process,” the biotech company noted in a report Press release from August 2023. The planned action date for the first part is October 8th and covers dosing over a period of 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 portion by the end of 2024.