FDA Acceptance of ALKS 3831 New Drug Application for Treatment of Schizophrenia and Bipolar Disorder

 Alkermes plc (Nasdaq: ALKS) announced that the U.S. Food and Drug Administration (FDA) has accepted for review the company's New Drug Application (NDA) seeking approval of ALKS 3831 (olanzapine/samidorphan) for the treatment of schizophrenia and for the treatment of bipolar I disorder. ALKS 3831 is an investigational, novel, once-daily, oral atypical antipsychotic drug candidate designed to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The NDA has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of Nov. 15, 2020. [(Olanzapine/samidorphan - developmental code name ALKS-3831) is a combination of the atypical antipsychotic olanzapine and the opioid modulator samidorphan

                             

                                                                                             Samidorphan

olanzapine

"The acceptance of the NDA for ALKS 3831 marks an important milestone toward our goal of offering a new treatment option to people living with schizophrenia or bipolar I disorder. The ALKS 3831 development program builds on Alkermes' commitment to developing new therapeutic options that seek to address unmet needs of patients in large therapeutic areas," said Craig Hopkinson, M.D., Chief Medical Officer at Alkermes. "We believe ALKS 3831 has the potential to be a meaningful new offering for patients with these serious and complex mental health disorders, and we look forward to engaging with the FDA throughout the NDA review process."

The ALKS 3831 NDA includes data from the ENLIGHTEN clinical development program in patients with schizophrenia, as well as pharmacokinetic (PK) bridging data comparing ALKS 3831 and ZYPREXA^® (olanzapine), to support an indication for the treatment of schizophrenia, and an indication for the treatment of manic or mixed episodes associated with bipolar I disorder as a monotherapy or adjunct to lithium or valproate and for maintenance treatment of bipolar I disorder. Alkermes is seeking approval of fixed dosage strengths of ALKS 3831 composed of 10 mg of samidorphan co-formulated with 5 mg, 10 mg, 15 mg or 20 mg of olanzapine.

About the ENLIGHTEN Clinical Development Program

The ENLIGHTEN clinical development program for ALKS 3831 includes two key studies in patients with schizophrenia: the ENLIGHTEN-1 study, which evaluated the antipsychotic efficacy of ALKS 3831 compared to placebo over four weeks, and the ENLIGHTEN-2 study, which assessed weight gain with ALKS 3831 compared to olanzapine over six months. The program also includes supportive studies to evaluate the pharmacokinetic and metabolic profile and long-term safety of ALKS 3831, and pharmacokinetic bridging studies comparing ALKS 3831 and ZYPREXA.

About ALKS 3831

ALKS 3831 is an investigational, novel, once-daily, oral atypical antipsychotic drug candidate for the treatment of schizophrenia and bipolar I disorder. ALKS 3831 is composed of samidorphan, a novel, new molecular entity, co-formulated with the established antipsychotic agent, olanzapine, in a single bilayer tablet.

About Schizophrenia 

Schizophrenia is a serious brain disorder marked by positive symptoms (hallucinations and delusions, disorganized speech and thoughts, and agitated or repeated movements) and negative symptoms (depression, blunted emotions and social withdrawal).An estimated 2.4 million American adults have schizophrenia, with men and women affected equally.

About Bipolar I Disorder

Bipolar disorder is a brain disorder that causes shifts in a person's mood, energy and ability to function. Patients with this brain disorder may experience debilitating mood shifts from extreme highs (mania) to extreme lows (depression). Bipolar I disorder is characterized by the occurrence of at least one manic episode, with or without the occurrence of a major depressive episode, and affects approximately one percent of the adult population in the United States in any given year.

About Alkermes plc

Alkermes plc is a fully integrated, global biopharmaceutical company developing innovative medicines for the treatment of central nervous system (CNS) diseases and oncology. The company has a diversified commercial product portfolio and a clinical pipeline of product candidates for diseases that include schizophrenia, depression, addiction, multiple sclerosis, and cancer. Headquartered in Dublin, Ireland, Alkermes plc has an R&D center in Waltham, Massachusetts; a research and manufacturing facility in Athlone, Ireland; and a manufacturing facility in Wilmington, Ohio. For more information, please visit Alkermes' website at www.alkermes.com.

https://en.wikipedia.org/wiki/Olanzapine

https://en.wikipedia.org/wiki/Samidorphan

Antipsychotic drug could help reduce nausea and vomiting caused by chemotherapy

In continuation of my update on Olanzapine

A drug that blocks neurotransmitters could reduce nausea and vomiting caused by chemotherapy, research co-authored by a Sanford Health physician and published in theNew England Journal of Medicine finds.

Sanford oncologist and cancer researcher Steven Powell, M.D., was among a team of researchers who discovered that the drug olanzapine, which is FDA approved for use as an antipsychotic agent, significantly improved nausea prevention in patients who were receiving chemotherapy for cancer treatment. The drug blocks neurotransmitters involved with nausea and vomiting.

"We've long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients," said Powell. "The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer."

Researchers noted that within the first day after treatment, 74 percent of study participants experienced no nausea or vomiting when their chemotherapy was paired with olanzapine. When a placebo was used instead of olanzapine, that figure dropped to 45 percent. This benefit continued for five days after chemotherapy treatment for many patients.

Ref : http://www.sanfordhealth.org/newsroom/2016/07/sanford-physician-assists-in-developing-new-treatment

Antipsychotic drug could help reduce nausea and vomiting caused by chemotherapy

FDA approves Olanzapine as Extended Release Injectable Suspension.....

In continuation of my update on drug development for schizophrenia , am sharing this info. The U.S. Food and Drug Administration (FDA) approved ZYPREXA RELPREVV (olanzapine) For Extended Release Injectable Suspension for the treatment of schizophrenia in adults. Different from both oral and injected short-acting formulations, long-acting formulations of antipsychotics allow for stable concentrations of the active drug to remain at a therapeutic range for an extended period of time.

The FDA approval is based on a broad clinical data package involving 2,054 patients, in which ZYPREXA RELPREVV was found to be effective in controlling symptoms of schizophrenia, including hallucinations, delusions, apathy and social withdrawal. Efficacy was shown without the need for oral supplementation. Clinical data showed that ZYPREXA RELPREVV dosages (150, 210, 300 and 405 mg) provide therapeutic olanzapine exposure for two or four weeks depending on the dose. More interesting outcome from these trials is that ZYPREXA RELPREVV was found to have a similar safety profile as oral olanzapine, with the exception of injection-related events, including post-injection delirium/sedation syndrome (PDSS).

PDSS events have occurred in < 0.1 percent of injections and approximately 2 percent of patients. The potential for onset of an event is greatest within the first hour after injection. The majority of cases have occurred within the first three hours after injection; however cases have occurred after three hours. All patients largely recovered within 72 hours.....

Ref : http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=429876

Olanzapine as long-acting injection (LAI) for acute and maintenance treatment of schizophrenia.?

Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine) is one of the most commonly used drugs for atypical antipsychotics. Olanzapine has been approved by the FDA for the treatment of schizophrenia, acute mania in bipolar disorder, agitation associated with schizophrenia and bipolar disorder, and as maintenance treatment in bipolar disorder and psychotic depression. Zyprexa is Lilly’s top-selling drug, with sales of $4.2 billion last year.

Olanzapine's antipsychotic activity is mediated primarily by antagonism (blocking or inhibition) at dopamine receptors.

FDA required the manufacturers of all atypical antipsychotics to include a warning about the risk of hyperglycemia and diabetes with atypical antipsychotics.

Lilly is continuing to work with the agency on the new drug application (NDA). I think Lilly, has a come with a smart move like NDA, becoz., the FDA does not require any additional clinical trials for the continued review of the NDA. Per the agency's request, Lilly is preparing a proposed Risk Evaluation and Mitigation Strategy (REMS), which will be submitted in the near future. Hope this drug will not have the said side effects. A ray of hope for schizophrenia patients ? time will tell the story, best of luck Lilly....

Antipsychotic drug, Olanzapine, may be helpful treatment for anorexia nervosa

In continuation of my update on Olanzapine..

Low doses of a commonly used atypical antipsychotic drug improved survival in a mouse model of anorexia nervosa, University of Chicago researchers report this month. The result offers promise for a common and occasionally fatal eating disorder that currently lacks approved drugs for treatment.

Antipsychotic drug may be helpful treatment for anorexia nervosa

Antipsychotic drug may be helpful treatment for anorexia nervosa

In continuation of my update on Olanzapine...

Antipsychotic drug may be helpful treatment for anorexia nervosa

INNOPHARMA Receives FDA Approval of Generic Levetiracetam Injection

In continuation of my update on Olanzapine......

INNOPHARMA Receives FDA Approval of Generic Levetiracetam Injection

FDA's approval of Iloperidone for schizophrenia....

Iloperidone

We did know about the "azepines" for treatment of schizophrenia, but this is a benzisoxazole derivative something interesting. Iloperidone, 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone. The advantage, the researcher claims is that, Iloperidone acts on both dopamine and serotonin receptors, making it a favorable choice against competing drugs clozapine and olanzapine. Clinical studies have shown that some patients treated with iloperidone show reduced extrapyramidal symptoms and weight gain. Phase II testing has shown that effectiveness in humans is possible with as low as 8mg per day, and is tolerable up to 32mg per day. The common side effects with this drug are dizziness, dry mouth, fatigue, nasal congestion, sudden fall in blood pressure causing light-headedness upon standing (orthostatic hypotension), drowsiness, rapid heart rate (tachycardia) and weight increase.

Ref :http://www.fda.gov/bbs/topics/NEWS/2009/NEW02009.html