FDA Updates for the Week of Sept. 11, 2023

FDA Approves Aphexda for Use in Stem Cell Mobilization.

The FDA has approved BioLineRx’s Aphexda (motixafortide) in stem cell mobilization for autologous transplantation in patients with multiple myeloma. Aphexda is administered by injection and is indicated to be used along with filgrastim (G-CSF). It will be available later this month.

Aphexdra will have a list price 5,900 per vial, according to a spokesperson. Dosing for Aphexdra is based on weight, and the company expects that based on the average weight of patients with multiple myeloma, most patients will require two vials.

Payers, a spokesperson said, have viewed the clinical data favorably. BioLineRx has met with payers covering more than 90% of commercially covered lives, which includes both commercial payers and CMS. A support program called, BioLineRx Connect, is designed to assist patients with insurance coverage, financial support, the payer process, and additional resources.

FDA Extends Review for Lifileucel to Treat Melanoma.

The FDA has extended the Prescription Drug User Fee Act (PDUFA) date for Iovance Biotherapeutics’ lifileucel to treat patients with advanced melanoma from Nov. 25, 2023, to Feb. 24, 2024. Agency officials said they need more time because of resource constraints.

The review of the biologics license application continues under priority review. The FDA indicated there are no major review issues, and there are no plans to hold an advisory committee meeting. In addition, all preapproval inspections of clinical sites, manufacturing and testing facilities have been completed.

Lifileucel is a tumor-infiltrating lymphocyte (TIL) therapy designed for patients with advanced melanoma who have experienced progression after previous treatment. If approved, it would be the first TIL therapy for patients with advanced melanoma and the first one-time cell therapy for a solid tumor cancer.

FDA Sets PDUFA Date for Resmetirom to Treat Patients with NASH.

The FDA has accepted the new drug application (NDA) seeking accelerated approval for Madrigal Pharmaceuticals’ resmetirom to treat adult patients with nonalcoholic steatohepatitis (NASH) who have liver fibrosis. The agency has granted priority review and assigned a Prescription Drug User Fee Act date for resmetirom of March 14, 2024.

Nonalcoholic steatohepatitis is a more advanced form of nonalcoholic fatty liver disease (NAFLD), which is estimated to affect about 30% adults in the United States. NASH is a leading cause of liver-related mortality, especially for those with more advanced metabolic risk factors such as hypertension and type 2 diabetes.

In NASH, thyroid hormone beta activity in the liver is impaired, leading to a reduction in mitochondrial function and beta-oxidation of fatty acids, which in turn drive inflammation and liver fibrosis. Resmetirom is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist

FDA Assigns Review Date for Libervant Film for Young Children.

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target goal date for April 28, 2024, for Aquestive Therapeutics’ Libervant (diazepam) buccal (inside of the cheek) film for children between two and five years of age. If approved, it would treat intermittent, stereotypic episodes of frequent seizure activity in these patients.

In August 2022, the FDA issued a tentative approval of Libervant to treat intermittent, stereotypic episodes of frequent seizure activity in those 12 years of age and older. It can be administered with or without food, which company executives said is important for acute use. But Libervant is not expected to be available until January 2027 because of existing orphan drug market exclusivity held by Valtoco (diazepam) nasal spray. Valtoco was approved by the FDA in January 2020 and its marketing exclusivity ends Jan. 10, 2027. Before Valtoco’s approval, current standard of care was a rectal gel formulation of diazepam.

FDA Advisory Committee Backs Use of Onpattro in Heart Failure Indication.

The FDA’s Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted 9 to 3 in support of Alnylam Pharmaceutical’s Onpattro (patisiran), which is being reviewed by the agency to treat patients with cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis. The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of Oct. 8, 2023.

ATTR amyloidosis is a rare, progressive, debilitating disease caused by misfolded transthyretin proteins that accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal tract.

Even though committee members voted in support of Onpattro, there were questions about whether it provided a clinically meaningful benefit.

Committee member Ravi I. Thadhani, M.D., executive vice president for health affairs at Emory University, voted yes and said that with a rare disease such ATTR that options and alternatives are critical. “There is a continuous decline in cardiac function and worsening of disease in patients who have received the current standard of care,” he said. “The benefits outweighed the risks for me. Clinical meaningfulness is subjective, as we’ve heard.”