FDA Action Alert: Alexion, Biogen, Vertex and Royalty


June is turning out to be a busy month for PDUFA dates for the U.S. Food and Drug Administration (FDA). Here’s a look at this week’s dates.

Alexion’s Ultomiris for Paroxysmal Nocturnal Hemoglobinuria (PNH)

Alexion Pharmaceuticals has a target action date of June 7, 2021, for its Ultomiris in children and adolescents with Paroxysmal Nocturnal Hemoglobinuria (PNH). Ultomiris (ravulizumab) is a long-acting C5 complement inhibitor. It is approved for adults with PNH and for adults and children one month of age and older with atypical Hemolytic Uremic Syndrome (aHUS). PNH is a rare blood causes that causes red blood cells to break apart, or hemolyze. This is the results of a missing protein in the patient’s blood cells. aHUS is an extremely rare disease marked by low levels of circulating red blood cells because of hemolytic anemia, low platelet count (thrombocytopenia) because of their consumption and inability for the kidneys to process waste products from the blood and excrete them into the urine (uremia). The application is under Priority Review.

On May 11, Alexion shareholders approved the acquisition of the company by AstraZeneca. The deal was originally announced in December 2020 and runs about $39 billion. AstraZeneca focuses on oncology, cardiovascular, renal and metabolism and respiratory diseases. It has increased its immunology research-and-development programs associated with immune-mediated diseases, which is partially why it is interested in Alexion. Alexion’s focus is on complement inhibition; complement is a part of the human immune system.

Biogen’s Aducanumab for Alzheimer’s Disease

In one of the most-watched decisions in recent years, Biogen has a target action date of June 7 for its aducanumab for Alzheimer’s disease. The drug is a monoclonal antibody against beta-amyloid, a sticky protein associated with the cognition and memory problems with Alzheimer’s disease. In March 2019, Biogen and Tokyo-based Eisai, announced they were discontinuing the global Phase III clinical trials, ENGAGE and EMERGE, of aducanumab in patients with mild cognitive impairment for Alzheimer’s and mild Alzheimer’s dementia, as well as the EVOLVE Phase II trial and the long-term extension PRIME Phase Ib trial. An independent data monitoring committee indicated they were unlikely to hit their primary endpoint.

Then, in October 2019, Biogen and Eisai announced after fully analyzing the EMERGE data, they planned to pursue regulatory approval. The data, they said, demonstrated a significant decrease in clinical decline. The data is very complex and remains controversial. Biogen said the data from a subset of patients that received a high enough dose of the drug had significant benefits on measures of cognition and function, including memory, orientation, and language, as well as benefits on activities of daily living.

In November 2020, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee slammed the drug submission, voting against recommending the drug to the agency. They did not think Biogen’s data proved efficacy and they questioned its risk-reward profile. There was an original target action date in March, the FDA requested additional analyses and clinical data, which Biogen turned over. The agency viewed it a Major Amendment and pushed the target action date back to June 7.

Royalty Pharma and Vertex’s Trikafta for CF in Kids Ages 6-11

Royalty Pharma and Vertex Pharmaceuticals have a target action date of June 8 for the supplemental New Drug Application (sNDA) for Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to include children ages 6 through 11 years of age who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data. It was granted Priority Review.

Trikafta is approved for CF patients 12 years and older with at least one copy of the F508del mutation in the CFTR gene or another mutation that is response to the drug. CF is caused by a defective and/or missing CFTR protein caused by mutations in the CFTR gene. Children must inherit two defective CFTR genes, one from each parent, to have CF. CF is a progressive, multi-system disorder affecting the lungs, liver, GI tract, sinuses, sweat glands, pancreas and reproductive tract. It results in poor flow of salt and water in and out of the cells in numerous organs. In the lungs, this causes an accumulation of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage that often leads to death.

On May 20, 2021, the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK validated the post marketing applications for the expanded indication (in those countries it is marketed as Kaftrio) in children ages six through 11. It was approved by the European Commission for children 12 years and older on April 28, 2021.

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