FDA Action Alert: Celgene, Amgen and Avadel
As we begin the final month of 2019, the U.S. Food and Drug Administration (FDA) has several PDUFA dates to approve drug applications. Here’s a look at those scheduled for the first two weeks of the month.
Celgene’s Luspatercept for Beta-thalassemia-associated Anemia
Celgene had a target action date of December 4, 2019 for its Biologics License Application (BLA) for luspatercept. Luspatercept is an investigational erythroid maturation agent for adults with very low to intermediate-risk myelodysplastic syndromes (MDS)-associated anemia who have ring sideroblasts and require red blood cell (RBC) transfusions, and for the treatment of adults with beta-thalassemia-associated anemia who require RBC transfusions—it is this second indication for which the company had the December 4 PDUFA date.
Luspatercept is also being reviewed by the European Medicines Agency (EMA). It is a first-in-class erythroid maturation agent (EMA) that regulates late-stage red blood cell maturation. The therapy was jointly developed by Celgene and Acceleron. The application was built on the results from the Phase III COMMANDS trial in ESA-naïve, lower-risk MDS patients and the Phase II BEYOND trial in non-transfusion-dependent beta-thalassemia.
The FDA approved luspatercept-aamt under the brand name of Reblozyl on November 8 for anemia in adults with beta-thalassemia. Beta-thalassemia is a rare, inherited blood disorder caused by a genetic defect in hemoglobin. The target action date for luspatercept for erythroid maturation agent for adults with very low to intermediate-risk myelodysplastic syndromes (MDS)-associated anemia who have ring sideroblasts and require red blood cell (RBC) transfusions is April 4, 2020.
Amgen’s Biosimilar to Janssen’s Remicade
Amgen has a target action date of December 14 for its BLA of ABP 710, a biosimilar candidate to Janssen Pharmaceutical’s Remicade (infliximab), a drug for various inflammatory diseases such as Crohn’s disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and plaque psoriasis.
ABP 710 (and infliximab) are anti-tumor necrosis factor alpha (anti-TNF) monoclonal antibodies. The BLA submission includes analytical, pharmacokinetic and clinical data in addition to pharmacology and toxicology data. A Phase III study comparing efficacy, safety and immunogenicity was run in patients with moderate-to-severe rheumatoid arthritis and confirmed no clinically meaningful differences between ABP 710 and infliximab.
Avadel’s FT218 for Narcolepsy
Avadel Pharma has a target action date of December 15 for AV001. The New Drug Application (NDA) was originally accepted in May 2019 under the FDA’s Priority Review program, which gives it a statutory six-month review. It was then extended by three months as the result of FDA requests for additional analytical information and Avadel’s resultant additional submissions.
FT218 is an investigational drug designed to be administered in one single dose, before bedtime, to treat excessive daytime sleepiness (EDS) and cataplexy in patients suffering from narcolepsy. It was granted orphan-drug designation by the FDA on January 8, 2018 on the theory that is may be clinically superior to the currently marketed, twice-nightly sodium oxybate product.
On November 25, 2019, Avadel announced it had completed patient enrollment of 205 patients in the REST-ON Phase III clinical trial for FT218. The enrollment target was 205 patients. Additional patients may be enrolled if they meet eligibility criteria. Topline data is expected in the second quarter of 2020.
The company says that if the drug is approved, it has the potential to capture a significant share of the twice-nightly sodium oxybate market, which is currently valued at $1.7 billion per year.
The REST-ON trial is a double-blind, randomized, placebo-controlled Phase III study to evaluate the efficacy and safety of once-nightly FT218. It is under a Special Protocol Assessment agreement with FDA.