New antipsychotic drugs! ALKS3831 (O nitrogenpin/samidorphan) was rejected by the FDA for treatment of schizophrenia/biphasia type I disorder

19, 2020 // -- Alkermes is a fully integrated Irish biopharmaceutical company dedicated to the development of innovative drugs for the treatment of central nervous system (CNS) diseases and tumors.
, the company announced that the U.S. Food and Drug Administration (FDA) has issued a full response letter (CRL) to the new drug application for the antipsychotic drug ALTDS3831 (olanzapine/samidorphan).
APKS3831 is a new, once-a-day atypical antipsychotic drug in study for the treatment of adult schizophrenia and adult biplex type 1 disorder.
a remote review of production records, the FDA said some issues related to the tablet garment process at the company's Wimington, Ohio, plant needed to be addressed before APKS3831 could be approved.
not found or raised any concerns about clinical or non-clinical data in the NDA in the CRL, and the FDA did not require Alkermes to complete any new clinical trials to support NDA approval.
the observations recorded in the CRL are specific to some development batches of APKS3831.
that the problem had been resolved and that there was enough data to handle the observations.
Alkermes is preparing to submit the data and plans to work closely with the FDA to resolve these issues in a timely manner and complete the labeling discussions for the application.
In accordance with fda industry guidelines for manufacturing inspections during the COVID-19 global pandemic in August 2020, during the review of the NDA, the agency did not conduct on-site pre-approval inspections (PAI) at Alkermes' manufacturing facility in Wimington, Ohio, but conducted a remote review of records under Section 704 (a) (4) of the Federal Food, Drug and Cosmetic Act.
FDA confirmed on September 11, 2020 that it had received the required records from Alkermes and that it had not provided Alkermes with a report or feedback on the records review prior to receipt of CRL as of that date. "We will continue to work closely with the FDA to support the approval of APKS3831 for the treatment of schizophrenia and bipolar disorder, and believe we have a clear solution," said Dr. Craig Hopkinson, chief medical officer and executive vice president of research and development at
Alkermes.
importantly, no clinical issues related to the efficacy or safety of APKS3831 have been found in the CRL and no new studies are required to support the application for approval.
, the FDA Advisory Committee on Psychoplytics and the Advisory Committee on Drug Safety and Risk Management met to discuss APKS3831.
committee voted that Samidorphan had meaningfully reduced the weight gain caused by olanzapine (16 votes in favour, 1 against) and that the safety characteristics of ALKS3831 were fully described (13 votes in favour, 3 against, 1 abstention).
, the committee voted jointly that drug labeling was sufficient to mitigate the risks associated with the effects of samidorphan opioid antagonists (11 votes in favor and 6 against).
Alkermes' proposed drug labeling bans the use of APKS3831 in patients who are dependent on or long-term opioid users, the company has also proposed a comprehensive education program that includes disseminating information to potential prescribers and pharmacists.
ALKD3831 is a double-layer tablet made from a novel new molecular entity, samidorphan (a new selective μ-opioid-agent antagonist), and a marketed antipsychotic drug, olanzapine.
and clinically related metabolic problems are common side effects of atypical anti-schizophrenic drugs.
is an effective antipsychotic drug, but clinical use is limited by its high-risk weight gain.
design of ALKD3831 seeks to improve the safety of treatment by reducing the side effects on weight and metabolism while providing strong antipsychotic effects.
APKS3831 is a new oral atypical antipsychotic drug developed once a day to treat schizophrenia and bisphonial type I disorders.
the drug is designed to provide the efficacy of olanzapine while reducing the weight gain caused by olysine.
, ALKS3831 is currently under review by the FDA with a target date of November 15, 2020.
ALKS3831 has 4 fixed dose combinations, consisting of 10 mg doses of samidorphan and different doses of oestration (5 mg, 10 mg, 15 mg, 20 mg).
ALKD3831 NDA includes data from ENLIGHTEN clinical development projects in patients with schizophrenia (including 2 key Phase III studies ENLIGHTEN-1.com, ENLIGHTEN-2) and comparison of ALK S3831 and the listed drug Zyprexa pharmacodynamics (PK) bridge research data to support the treatment of schizophrenia adaptation, as well as the treatment of bipolar disorder or mixed seizures associated with bipolar disorder as a single drug or as an ancillary therapy for lithium or sodium valproate.
ENLIGHTEN-1 is a 4-week randomized, double-blind Phase III study conducted in patients with schizophrenia who are experiencing acute exacerbation, comparing the antipsychotic efficacy, safety and tolerance of APKS3831 relative to placebo.
results showed that the study reached its primary endpoint: the positive and negative symptom scale (PANSS) scores of the ALKS3831 treatment group showed a significant statistically significant decrease compared to the placebo group.
the study also included a group of otoxyntherapy groups, but not to compare the efficacy or safety between APKS3831 and oxypine.
study data showed a similar improvement in the pansS score relative to baseline changes in the on-nitrogen treatment group compared to the placebo group.
ENLIGHTEN-2 is a six-month book, double-blind Phase III study that assessed the weight effects of APKS3831 and placebo in patients with stable schizophrenia.
results showed that the study reached a common primary endpoint, showing that the ALKS3831 treatment group had a lower average percentage of weight gain from baseline at the 6th month of treatment and a lower percentage of patients who gained ≥10% in the 6th month of treatment≥
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