FDA Action Alert: Supernus, Adamis, Alkermes, Amgen, BMS and Eiger

November is promising to be a busy month for the U.S. Food and Drug Administration (FDA) in terms of PDUFA dates. Here’s a look at some of the upcoming target action dates on the FDA’s calendar. 

Supernus Pharmaceuticals’ SPN-812 for ADHD

Supernus Pharmaceuticals has a target action date of November 8, 2020 for SPN-812 for the treatment of attention deficit hyperactivity disorder (ADHD). SPN-812 is a serotonin norepinephrine modulating agent (SNMA). The active ingredient is violaxazine hydrochloride, which has an extensive safety record in Europe, where it was previously marketed as an antidepressant.

The New Drug Application (NDA) for the drug is based on data from four Phase III trials in pediatric patient populations from the age of 6 to 17 years, two Phase II trials, several Phase I trials, a long-term open label extension study, preclinical testing, and drug manufacturing data. The company is also still conducting a Phase III trial in the adult ADHD patient population.

Adamis Pharmaceuticals’ Zimhi for Opioid Overdose

Adamis Pharmaceuticals has a target action date of November 15 for its Zimhi (naloxone) for opioid overdose. The NDA was resubmitted on May 2020. The resubmission came after a meeting with the FDA in February 2020 and addresses issues raised by the agency’s Complete Response Letter (CRL) in November 2019.

“We have been encouraged by our interactions with the FDA following our CRL and are pleased to resubmit our Zimhi NDA,” said Dennis J. Carlo, president and chief executive officer of Adamis, in May 2020. “Based on the feedback from our Type A meeting in February, we conducted additional product testing with the goal of addressing the Chemistry, Manufacturing and Controls deficiencies discussed in the CRL.”

Alkermes’ ALKS 3831 for Schizophrenia and Bipolar I Disorder

Alkermes has a target action date of November 15 for ALKS 3831 (olanzapine/samidorphan) for the treatment of schizophrenia and for the treatment of bipolar I disorder. The drug is an investigational, novel, once-daily, oral atypical antipsychotic drug candidate designed to improve the efficacy of olanzapine while decreasing olanzapine-associated weight gain.

The submission includes data from the ENLIGHTEN clinical development program in schizophrenia, and pharmacokinetic (PK) bridging data comparing ALKS 3831 and Zyprexa (olanzapine), to support an indication for schizophrenia. There is also data supporting treatment of manic or mixed episodes linked with bipolar I disorder as a monotherapy or adjunct to lithium or valproate for maintenance of bipolar I disorder.

Amgen’s Kyprolis in R/R Multiple Myeloma

Amgen has a target action date of November 15 for the supplemental NDA (sNDA) for Kyprolis in combination with dexamethasone and Darzalex (daratumumab) for relapsed or refractory (R/R) multiple myeloma. The sNDA was built on data from the Phase III CANDOR trial.

In September 2019, the company announced the CANDOR trial met its primary endpoint of progression-free survival (PFS), showing a 37% decrease in the risk of progression or death in patients with r/r multiple myeloma treated with dexamethasone and Darzalex.

“The potential to combine Kyprolis and Darzalex, two powerful targeted agents, represents an additional therapeutic approach for patients with relapsed or refractory multiple myeloma,” said David M. Reese, executive vice president of Research and Development at Amgen. “The results from the CANDOR study confirm the potential for Kyprolis to be used in combination with an anti-CD38 monoclonal antibody.”

Bristol Myers Squibb’s Lisocabtagene Maraleucel (CAR-T) for R/R Large B-Cell Lymphoma

Bristol Myers Squibb has a target action date of November 16 for the biologics license application (BLA) for lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T cell therapy for adults with r/r large B-cell lymphoma after at least two previous therapies. Prior to the submission and acceptance of the SBA, ZBMS had submitted additional data, which the agency defined as a major amendment to the application and would require additional time for review.

Bristol Myers Squibb picked up liso-cel when it acquired Celgene. Celgene acquired it in 2018 from bluebird bio, who originally developed the therapy. When BMS was putting in its bid for Celgene, the two companies could not agree on the long-term value of Zeposia (ide-cel), which is approved for multiple sclerosis, and liso-cel. To close the deal, they agreed that if Zeposia and liso-cel were approved by December 31, 2020, and ide-cel by March 31, 2021, Bristol Myers Squibb would pay another $9 per share via a Contingent Value Right (CVR). This seemed likely until the FDA pushed back the ide-cel review.

Eiger BioPharmaceuticals’ Zokinvy for Progeria and Progeroid Laminopathies

Eiger BioPharmaceuticals has a target action date of November 20 for Zokinvy (lonafarnib) for Progeria and Progeroid Laminopathies. This is under Priority Review. The NDA included data from Phase III trial demonstrating a survival benefit with an 88% decrease in the risk of mortality in patients with Progeria treated with Ionafarnib monotherapy. Progeria, also called Hutchinson-Gilford Progeria Syndrome (HGPS), is an ultra-rare and fatal genetic disease of accelerated aging in children. It is caused by a point mutation in the LMNA gene, which codes for the lamin A protein, resulting in the farnesylated aberrant protein, progerin. Without Ionafarnib therapy, children with Progeria die of artheroschlerosis, but at an average age of 14.5 years. Progeroid Laminopathies are similar, caused by a number of mutations in the lamin A and/or Zmpste24 genes.

“The acceptance of our first NDA is a significant milestone for Eiger, and an important step toward bringing a treatment to children and young adults with Progeria and Progeroid Laminopathies,” said David Cory, president and chief executive officer of Eiger.