Cidara Therapeutics Announces FDA Acceptance for Priority Review of New Drug Application for Rezafungin for the Treatment of Candidemia and Invasive Candidiasis

Cidara Therapeutics, Inc.  , a biotechnology company developing long-acting therapeutics designed to improve the standard of care for patients facing serious diseases,  announced   the  FDA acceptance for filing and granted Priority Review to its New Drug Application (NDA) for rezafungin for the treatment of candidemia and invasive candidiasis. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 22, 2023 enabled by rezafungin’s designation as a Qualified Infectious Disease Product (QIDP) and has indicated that it is currently planning to hold an advisory committee meeting to discuss the application. QIDP designation is reserved for antibacterial and antifungal drug candidates intended to treat serious or life-threatening infections. Rezafungin is a novel, once-weekly echinocandin antifungal being developed for the treatment of candidemia and invasive candidiasis, as well as for the prophylaxis of invasive fungal infections in patients undergoing allogeneic blood and marrow transplant.

“Today’s announcement is an important step forward for patients fighting difficult-to-treat and often deadly candidemia and invasive candidiasis, and represents a critical milestone for Cidara’s rezafungin development program,” said Jeff Stein, President, and CEO of Cidara Therapeutics. “The data generated across our Phase 2 and Phase 3 trials demonstrated that rezafungin could transform the current standard of care for the treatment of invasive Candida infections, and we are excited that rezafungin could potentially be the first new drug approved for this indication in over a decade.”

The NDA submission for rezafungin was supported by positive clinical data from the global ReSTORE Phase 3 and STRIVE Phase 2 clinical trials. Rezafungin dosed once-weekly demonstrated statistical non-inferiority versus caspofungin, the current standard of care, dosed once-daily, meeting the primary endpoints for both the FDA and the European Medicines Agency (EMA).

Cidara retains the rights to rezafungin in Japan and has licensed the commercial rights to Melinta Therapeutics in the U.S. and Mundipharma Medical in all other geographies.

About Rezafungin

Rezafungin is a novel once-weekly echinocandin being developed for both the treatment and prevention of serious fungal infections, such as candidemia and invasive candidiasis. The structure and properties of rezafungin are specifically designed to improve upon a clinically validated mechanism intended to enhance its efficacy and safety potential for patients. Cidara has completed a Phase 3 clinical trial with rezafungin for the first-line treatment of candidemia and/or invasive candidiasis (ReSTORE trial) and is currently conducting a second Phase 3 clinical trial of rezafungin for the prevention of invasive fungal disease in patients undergoing allogeneic blood and marrow transplantation (ReSPECT trial). Rezafungin has been designated a QIDP with Fast Track status by the FDA, and has been granted Orphan Drug Designation for its use in the treatment of invasive candidiasis in both the U.S. and EU.

Acadia Pharmaceuticals Announces Trofinetide New Drug Application for the Treatment of Rett Syndrome has been Accepted for Filing and Review by U.S. FDA

About Rett Syndrome

Rett syndrome is a rare genetic neurodevelopmental disorder that occurs primarily in females following a near normal development in the first two years of life.  It is caused by mutations on the X chromosome on a gene called MECP2.  Occurring worldwide in approximately one of every 10,000 to 15,000 female births and in the United States impacts 6,000 to 9,000 patients.  Children with Rett syndrome experience a period of developmental regression between 18-30 months of age, which is typically followed by a plateau period lasting years to decades. Rett syndrome is diagnosed based on clinical evaluation, typically by about three years of age

A complex and multisystem disorder, Rett syndrome causes profound impairment to central nervous system (CNS) function, including loss of communication skills, purposeful hand use, gait abnormalities, and stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing and washing/rubbing automatisms.   People living with Rett syndrome may also experience a range of additional symptoms, such as gastrointestinal complications, skeletal abnormalities, neuroendocrine abnormalities, disruptive and anxiety-like behaviors, as well as mood dysregulation and sleep disturbances. Currently, there are no FDA-approved medicines for the treatment of Rett syndrome.

About Trofinetide

Trofinetide is an investigational drug. It is a novel synthetic analog of the amino‐terminal tripeptide of IGF-1 designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function. Trofinetide is thought to stimulate synaptic maturation and overcome the synaptic and neuronal immaturities that are characteristic of Rett syndrome pathophysiology. In the central nervous system, IGF-1 is produced by both of the major types of brain cells – neurons and glia. IGF-1 in the brain is critical for both normal development and for response to injury and disease. Trofinetide has been shown to inhibit the production of inflammatory cytokines, inhibit the overactivation of microglia and astrocytes, and increase the amount of available IGF-1 that can bind to IGF-1 receptors.

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

Acadia Pharmaceuticals Inc.  announced   the U.S. Food and Drug Administration (FDA)  acceptance  for filing its New Drug Application (NDA) of trofinetide for the treatment of Rett syndrome. The FDA has granted a priority review and assigned a PDUFA (Prescription Drug User Fee Act) action date of March 12, 2023. The FDA has also informed the company that at this time they are not planning to hold an Advisory Committee meeting.

“We’re pleased that the FDA has accepted our NDA filing and we will be working closely with them to facilitate completion of the review in a timely manner,” said Steve Davis, Acadia’s Chief Executive Officer. “If approved, trofinetide will be the first drug available for the treatment of Rett syndrome, a rare and devastating condition for patients and their families. This milestone reinforces Acadia’s ongoing commitment to advancing research into high unmet needs in disorders affecting the central nervous system.”

Rett syndrome is a complex, multisystem neurodevelopmental disorder that includes a period of normal development followed by significant developmental regression with loss of language and hand function skills, impaired gait and development of hand stereotypes.1,2 It occurs worldwide in approximately one of every 10,000 to 15,000 female births.3

“Rett is a complex disease that can present with a diverse array of symptoms. In clinical trials, trofinetide demonstrated a significant improvement in a range of Rett syndrome symptoms,” said Jeffrey L. Neul, M.D., Ph.D., Annette Schaffer Eskind Chair and Director, Vanderbilt Kennedy Center, Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Phase 3 Lavender™ study investigator. “We look forward to the FDA’s review of this submission and the prospect of having access to the first approved treatment for Rett syndrome.”

The NDA is supported by results from the pivotal Phase 3 Lavender study evaluating the efficacy and safety of trofinetide versus placebo in 187 girls and young women aged 5-20 years with Rett syndrome. The study demonstrated a statistically significant improvement over placebo on the co-primary endpoints, the Rett Syndrome Behaviour Questionnaire (RSBQ) total score change from baseline to 12 weeks (p=0.0175; effect size=0.37) and the Clinical Global Impression-Improvement (CGI-I) scale score (p=0.0030; effect size=0.47). The RSBQ is a caregiver assessment of the core symptoms of Rett syndrome, and the CGI-I is a global physician assessment of worsening or improving of Rett syndrome. In addition, the study also met its key secondary endpoint, the Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist–Social Composite Score (CSBS-DP-IT–Social) change from baseline to week 12 (p=0.0064; effect size=0.43), a caregiver assessment of ability to communicate.

In 2018, Acadia entered into an exclusive license agreement with Neuren Pharmaceuticals Limited (ASX: NEU) for the development and commercialization of trofinetide for the treatment of Rett syndrome and other indications in North America. In addition to receiving priority review by the FDA, trofinetide has been granted Fast Track Status and Orphan Drug Designation for the treatment of Rett syndrome in the U.S. and has been granted Rare Pediatric Disease (RPD) designation by the FDA. Upon FDA approval of a product with RPD designation, the sponsor can receive a Priority Review Voucher, which can be used to obtain priority review for a subsequent application.

Spectrum Pharmaceuticals Submits New Drug Application for Poziotinib

Spectrum Pharmaceuticals, a biopharmaceutical company focused on novel and targeted oncology therapies, announced the submission of  its New Drug Application (NDA) for poziotinib to the U.S. Food and Drug Administration (FDA) for use in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations. The NDA submission is based on the positive results of Cohort 2 from the ZENITH20 clinical trial, which assessed the safety and efficacy of poziotinib. The product has received Fast Track designation and there is currently no treatment specifically approved by the FDA for this indication.

“The NDA submission for poziotinib marks an important step in achieving a first treatment for patients with HER2 exon 20 insertion mutations in lung cancer,” said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. “I want to thank the patients, investigators and our internal staff who have passionately worked to achieve this important milestone in an area of high unmet medical need.”

ZENITH20 Cohort 2 Clinical Results Summary

Results for Cohort 2 of the ZENITH20 clinical trial have been published in the Journal of Clinical Oncology (November 29, 2021), and can be accessed by clicking here.

Cohort 2 enrolled 90 patients who received an oral once daily dose of 16 mg of poziotinib. The intent-to-treat analysis demonstrated a confirmed objective response rate (ORR) of 27.8% (95% Confidence Interval (CI), 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The median duration of response was 5.1 months and the median progression free survival was 5.5 months. In this cohort, 87% of patients had drug interruptions with 11 patients (12%) permanently discontinuing due to adverse events. 13 patients (14%) had treatment-related serious adverse events. As previously announced, the company had a successful pre-NDA meeting with the FDA which resulted in an agreement to submit an NDA for poziotinib. During the meeting, Spectrum confirmed with the FDA that Cohort 2 data could serve as the basis of an NDA submission. The company will continue to work with the FDA as appropriate, while the agency conducts its review.

More : https://investor.sppirx.com/news-releases/news-release-details/spectrum-pharmaceuticals-submits-new-drug-application-poziotinib

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

New Drug Application for Tebipenem HBr for the Treatment of Complicated Urinary Tract Infections including Pyelonephritis

   

Spero Therapeutics, Inc. announced the submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA), seeking approval for tebipenem HBr tablets for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible microorganisms. If approved, tebipenem HBr would be the only oral carbapenem antibiotic available for use in cUTI.

“With the submission of this NDA, we have taken a major step towards potentially providing a substantial number of appropriate cUTI patients with an oral treatment option that could replace historical use of intravenous (IV) therapy,” said Ankit Mahadevia, M.D., Chief Executive Officer of Spero Therapeutics. “If approved, we believe tebipenem HBr could help patients significantly, and the avoidance of IV administration could lead to reduced healthcare resource utilization. We look forward to working with the FDA during the NDA review process as we prepare for tebipenem HBr’s anticipated launch in the second half of 2022.”

The NDA submission includes previously communicated positive data from the Phase 3 ADAPT-PO trial. This data showed that ADAPT-PO met its primary endpoint by demonstrating that oral tebipenem HBr was statistically non-inferior to IV ertapenem in the treatment of patients with cUTI and patients with acute pyelonephritis (AP).

https://pubchem.ncbi.nlm.nih.gov/compound/Tebipenem-pivoxil-hydrobromide

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

Spectrum Pharmaceuticals Submits New Drug Application for Poziotinib for metastatic NSCLC with HER2 exon 20 insertion mutations.

 

                  

Spectrum Pharmaceuticals, a biopharmaceutical company focused on novel and targeted oncology therapies,  announced that it has submitted its New Drug Application (NDA) for poziotinib to the U.S. Food and Drug Administration (FDA) for use in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations. The NDA submission is based on the positive results of Cohort 2 from the ZENITH20 clinical trial, which assessed the safety and efficacy of poziotinib. The product has received Fast Track designation and there is currently no treatment specifically approved by the FDA for this indication.

“The NDA submission for poziotinib marks an important step in achieving a first treatment for patients with HER2 exon 20 insertion mutations in lung cancer,” said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. “I want to thank the patients, investigators and our internal staff who have passionately worked to achieve this important milestone in an area of high unmet medical need.”

ZENITH20 Cohort 2 Clinical Results Summary

Results for Cohort 2 of the ZENITH20 clinical trial have been published in the Journal of Clinical Oncology (November 29, 2021), and can be accessed by clicking here.

Cohort 2 enrolled 90 patients who received an oral once daily dose of 16 mg of poziotinib. The intent-to-treat analysis demonstrated a confirmed objective response rate (ORR) of 27.8% (95% Confidence Interval (CI), 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The median duration of response was 5.1 months and the median progression free survival was 5.5 months. In this cohort, 87% of patients had drug interruptions with 11 patients (12%) permanently discontinuing due to adverse events. 13 patients (14%) had treatment-related serious adverse events. As previously announced, the company had a successful pre-NDA meeting with the FDA which resulted in an agreement to submit an NDA for poziotinib. During the meeting, Spectrum confirmed with the FDA that Cohort 2 data could serve as the basis of an NDA submission. The company will continue to work with the FDA as appropriate, while the agency conducts its review.

About the ZENITH20 Clinical Trial

The ZENITH20 study consists of seven cohorts of NSCLC patients. Cohorts 1 (EGFR) and 2 (HER2) in previously treated NSCLC patients with exon 20 mutations and Cohort 3 (EGFR) in first-line patients have completed enrollment. Cohort 4 (HER2) in first-line NSCLC patients with exon 20 mutations is still enrolling patients. Cohorts 1- 4 are each independently powered for a pre-specified statistical hypothesis and the primary endpoint is objective response rate (ORR). Cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Cohort 6 includes NSCLC patients with classical EGFR mutations who progressed while on treatment with first-line osimertinib and developed an additional EGFR mutation. Cohort 7 includes NSCLC patients with a variety of less common mutations in EGFR or HER2 exons 18-21 or the extracellular or transmembrane domains

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

Stealth BioTherapeutics Submits Elamipretide New Drug Application to FDA for Treatment of Barth Syndrome

 

Stealth BioTherapeutics Corp, announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Adminstration (FDA) for elamipretide, the company's lead product candidate, for the treatment of Barth syndrome, an ultra-rare genetic condition with no FDA- or EMA-approved therapies.

 

"Children and young adults affected by Barth syndrome are suffering from life limiting, progressive cardiomyopathy, exercise intolerance, and debilitating fatigue for which there are no approved treatment options," said Chief Executive Officer Reenie McCarthy. "We initiated our Barth syndrome development efforts at the request of the Barth syndrome community. We respect the patient community's perspective regarding its tolerance for some uncertainty of benefit in considering therapies for this ultra rare disease, and with our NDA submission, have answered its petition that we submit our application. We know that the FDA has similarly heard the voice of these patients, and we look forward to continued dialogue with the FDA as it evaluates our submission for filing and review."

The NDA submission is based on results from the SPIBA-001 Phase 3 Retrospective Natural History Control Trial, which compared data from the open-label portion of the TAZPOWER Phase 2/3 clinical trial to matched natural history controls. SPIBA-001 met its primary and most secondary endpoints, demonstrating elamipretide-mediated improvements in assessments of exercise tolerance, strength and cardiac function that are unexpected in the natural course of this progressively debilitating disease. In addition, improvements were observed during the TAZPOWER Phase 2/3 clinical trial and open label extension in several surrogate and intermediate clinical endpoints that may be reasonably likely to predict clinical benefit for patients suffering from this serious disease, potentially supporting an accelerated approval pathway. Although the FDA has recommended that additional controlled data be generated to support NDA review, neither the FDA nor the Company has identified a feasible trial design due to the ultra-rare nature of this disease. In light of FDA's view that the existing clinical data are insufficient to demonstrate substantial evidence of effectiveness and would not support NDA review, there is no assurance that the FDA will file the NDA. Stealth believes, however, that the data could support an NDA review, and has accordingly submitted the NDA as requested by the Barth syndrome patient community.

Elamipretide was previously granted rare pediatric designation, fast track designation, and orphan drug designation by the FDA, and orphan drug designation by the EMA, for the treatment of Barth Syndrome.  

About Barth Syndrome

Barth syndrome is an ultra-rare genetic condition characterized by cardiac abnormalities often leading to heart failure and reduced life expectancy, recurrent infections, muscle weakness and delayed growth. Barth syndrome occurs almost exclusively in males and is estimated to affect one in 200,000 to 400,000 individuals worldwide. There are currently no FDA- or EMA-approved therapies for patients with Barth syndrome.

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

Axsome Therapeutics Announces FDA Acceptance of New Drug Application for AXS-07 (meloxicam-rizatriptan) for the Acute Treatment of Migraine

 

In continuation of my update on meloxicam, 

Axsome Therapeutics, Inc.   that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s New Drug Application (NDA) for AXS-07 for the acute treatment of migraine, and has set a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2022 for the NDA. AXS-07 (MoSEIC™ meloxicam-rizatriptan) is a novel, oral, rapidly absorbed, multi-mechanistic, investigational medicine for migraine.

  

meloxicam

 

Rizatriptan

  “The FDA’s acceptance of the NDA for AXS-07 is an important milestone for Axsome as it brings us closer to potentially making this multi-mechanistic treatment available to migraine patients in need,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “We look forward to continued interactions with the FDA during the review process.”

The NDA is supported by results from two Phase 3 randomized, double-blind, controlled trials of AXS-07 in the acute treatment of migraine, the MOMENTUM and INTERCEPT trials, which demonstrated statistically significant elimination of migraine pain with AXS-07 compared to placebo and active controls.

AXS-07 is a novel, oral, rapidly absorbed, multi-mechanistic investigational medicine for the acute treatment of migraine, consisting of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug and rizatriptan is a 5-HT1B/1D agonist. AXS-07 is designed to provide rapid, enhanced and consistent relief of migraine, with reduced symptom recurrence. AXS-07 is covered by more than 80 issued U.S. and international patents which provide protection out to 2036. AXS-07 is not approved by the FDA.

https://pubchem.ncbi.nlm.nih.gov/compound/Rizatriptan

https://pubchem.ncbi.nlm.nih.gov/compound/Meloxicam#section=2D-Structure

Marinus Announces FDA Acceptance for New Drug Application for Ganaxolone in CDKL5 Deficiency Disorder

       

Marinus Pharmaceuticals, Inc.  announced  the U.S. FDA acceptance for filing the company’s New Drug Application (NDA) for the use of ganaxolone in the treatment of seizures associated with CDKL5 deficiency disorder (CDD), a rare, genetic epilepsy. The NDA was granted Priority Review designation and the FDA assigned a Prescription Drug User Fee Act (PDUFA) action date of March 20, 2022. Priority Review designation is given to an investigational medicine that, if approved, would be a significant improvement in the safety or effectiveness of the treatment of a serious condition and accelerates the timing of the FDA review of the application compared to a standard review.

“The FDA’s acceptance of our NDA submission is an important step toward potentially bringing the first approved therapy specifically for treatment of seizures associated with CDD—a devastating disorder with high unmet medical need—to families and healthcare providers,” said Scott Braunstein, M.D., Chief Executive Officer of Marinus Pharmaceuticals. “We believe that ganaxolone has the potential to provide meaningful clinical benefit for patients and we look forward to working closely with the FDA during the review process.”

Ganaxolone received orphan drug designation and Rare Pediatric Disease (RPD) designation for CDD in June 2017 and July 2020, respectively. If the NDA is approved, Marinus is eligible to receive a RPD Priority Review Voucher that may be sold or transferred.

In its acceptance letter, the FDA indicated that it is not currently planning to hold an advisory committee meeting to discuss the application.

The acceptance of the NDA for filing enables the company to draw $30 million of additional cash under its May 11, 2021 credit financing agreement with Oaktree Capital Management, L.P., subject to the satisfaction of certain customary conditions described in the credit agreement. If the NDA is approved by December 31, 2022, the company may draw an additional $30 million under the agreement, subject to the satisfaction of certain customary conditions described in the credit agreement.

The NDA is supported by data from the Marigold study, a Phase 3, double-blind placebo-controlled trial in 101 patients. Patients treated with ganaxolone showed a 30.7% median reduction in 28-day major motor seizure frequency, compared to a 6.9% reduction for those receiving placebo, achieving the trial’s primary endpoint (p=0.0036). Patients in the open-label extension study treated with ganaxolone for at least 12 months (n=48) experienced a median 49.6% reduction in major motor seizure frequency. In the Marigold trial, ganaxolone was generally well-tolerated and showed a safety profile consistent with previous clinical trials, with the most frequent adverse event being somnolence. 

Marinus has established an Expanded Access Program (EAP) (NCT04678479) for patients in the U.S. who may be eligible to receive access to ganaxolone during the review of the NDA. Additional information about Marinus’ EAP is available here.

More...

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

 

Spero Therapeutics Submits New Drug Application for Tebipenem HBr for the Treatment of Complicated Urinary Tract Infections including Pyelonephritis

   

Spero Therapeutics, Inc. announced the submission of a new drug application (NDA) to the U.S. Food and Drug Administration (FDA), seeking approval for tebipenem HBr tablets for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible microorganisms. If approved, tebipenem HBr would be the only oral carbapenem antibiotic available for use in cUTI.

“With the submission of this NDA, we have taken a major step towards potentially providing a substantial number of appropriate cUTI patients with an oral treatment option that could replace historical use of intravenous (IV) therapy,” said Ankit Mahadevia, M.D., Chief Executive Officer of Spero Therapeutics. “If approved, we believe tebipenem HBr could help patients significantly, and the avoidance of IV administration could lead to reduced healthcare resource utilization. We look forward to working with the FDA during the NDA review process as we prepare for tebipenem HBr’s anticipated launch in the second half of 2022.”

The NDA submission includes previously communicated positive data from the Phase 3 ADAPT-PO trial. This data showed that ADAPT-PO met its primary endpoint by demonstrating that oral tebipenem HBr was statistically non-inferior to IV ertapenem in the treatment of patients with cUTI and patients with acute pyelonephritis (AP).

More...

https://pubchem.ncbi.nlm.nih.gov/compound/Tebipenem-pivoxil-hydrobromide

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

Epizyme Announces FDA Filing Acceptance of New Drug Application and Priority Review for Tazemetostat for the Treatment of Epithelioid Sarcoma

Epizyme, Inc. (Nasdaq: EPZM), a late-stage biopharmaceutical company developing novel epigenetic therapies, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the company’s New Drug Application (NDA) for accelerated approval of tazemetostat, its lead investigational agent. Epizyme has proposed an indication of metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery. The FDA granted Priority Review for the NDA and has set a Prescription Drug User Fee Act (PDUFA) target action date of January 23, 2020. Priority Review is granted to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention or diagnosis of a serious condition.

“We are thrilled with FDA’s acceptance of this first tazemetostat NDA submission for priority review, and to be an important step closer to achieving our mission of rewriting treatment for patients with cancer and other serious diseases,” said Robert Bazemore, president and chief executive officer of Epizyme. “This is a significant achievement in the development of this potentially first-in-class EZH2 inhibitor, and we look forward to working with FDA during the review. If approved, we believe tazemetostat could become an important new option in the treating physicians’ arsenal. We would like to extend our sincerest gratitude to those patients, families and medical teams who have participated in our clinical studies and helped bring tazemetostat to this stage.”

Epizyme’s NDA submission is based primarily on data from the 62 patient epithelioid sarcoma cohort of its ongoing Phase 2 study of tazemetostat. These data, recently reported at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that tazemetostat treatment resulted in clinically meaningful and durable responses, and was generally well-tolerated.

To support full approval of tazemetostat for epithelioid sarcoma, Epizyme will initiate a global confirmatory trial. The company plans to conduct a 1:1 randomized, controlled clinical trial in the front-line treatment setting comparing tazemetostat in combination with doxorubicin versus placebo plus doxorubicin in approximately 150 patients. The primary efficacy endpoint will be progression-free survival, and secondary efficacy endpoints will include overall survival, disease control rate, overall response rate and duration of response. The confirmatory study will include a safety run-in that is expected to begin in the second half of 2019.

About the Tazemetostat Clinical Trial Program 

Tazemetostat, an oral, potent, first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing clinical programs in patients with certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors, and in patients with follicular lymphoma, both with and without EZH2 activating mutations. Multiple clinical studies are underway through collaborations assessing tazemetostat as a combination treatment for patients with diffuse large B-cell lymphoma. Epizyme also plans to conduct multiple additional clinical trials designed to evaluate the potential benefit of tazemetostat in earlier lines of therapy for follicular lymphoma, as well as new combinations and cancer indications.

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

Sunovion Announces Acceptance by the U.S. FDA of the New Drug Application for Dasotraline for the Treatment of Adults with Moderate-to-Severe Binge Eating Disorder

In continuation of my update on dasotraline,

Sunovion Pharmaceuticals Inc.(Sunovion) today announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for dasotraline, a novel dopamine and norepinephrine reuptake inhibitor (DNRI), for the treatment of patients with moderate-to-severe binge eating disorder (BED). Dasotraline’s pharmacokinetic profile, characterized by an extended half-life, supports its potential for sustained control of moderate-to-severe BED symptoms.

The action date by the FDA under the Prescription Drug User Fee Act (PDUFA) is May 14, 2020.

Dasotraline is an investigational, once-daily medication that demonstrated significant efficacy for the treatment of moderate-to-severe BED in two 12-week, randomized, placebo-controlled studies, SEP360-221 and SEP360-321. Dasotraline was found to be generally well tolerated in clinical studies, including a long-term safety study, SEP360-322, that assessed patients with moderate-to-severe BED for up to one year.

“Binge eating disorder is a serious mental health condition for which limited treatment options exist. The disorder is often seen in association with other behavioral conditions such as depression, substance abuse and post-traumatic stress disorder, and it is often under-diagnosed and under-treated,” said Antony Loebel, M.D., President and Chief Executive Officer at Sunovion. “We are confident in the value dasotraline has shown in clinical trials to people living with BED and look forward to working with the FDA to advance this novel treatment option.”

According to the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5),2,3 BED is characterized by recurrent and persistent episodes of binge eating, defined as consuming large quantities of food in a short period of time, perception of loss of control during the episode, and intense feelings of shame, guilt and embarrassment afterwards. Many individuals also suffer from depressive and anxiety symptoms, as well as a number of medical complications, leading to impaired functioning and quality of life.

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

Blueprint Medicines Announces FDA Acceptance of New Drug Application for Avapritinib for the Treatment of PDGFRA Exon 18 Mutant GIST and Fourth-Line GIST

Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced that the U.S. Food and Drug Administration (FDA) has accepted the company's New Drug Application (NDA) for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant gastrointestinal stromal tumors (GIST), regardless of prior therapy, and fourth-line GIST. The FDA granted Priority Review and set an action date of February 14, 2020 under the Prescription Drug User Fee Act (PDUFA). At this time, the FDA is not planning to hold an advisory committee meeting to discuss this application. Avapritinib, an investigational therapy, is a potent and highly selective KIT and PDGFRA inhibitor for patients with advanced GIST.

"Patients with PDGFRA Exon 18 mutant GIST and fourth-line GIST are in need of new treatment options that address the underlying drivers of the disease," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "The FDA's acceptance of our application for Priority Review brings us closer to our goal of delivering avapritinib to patients with GIST, and we look forward to working closely with the FDAduring the review process."

The FDA's acceptance of the NDA indicates the application is sufficiently complete to permit a substantive review. A Priority Review designation accelerates the FDA's review time from 12 months to a goal of eight months from the NDA submission date, and is granted to drugs that may offer a significant improvement in the safety or effectiveness of the treatment, prevention or diagnosis of a serious condition. Previously, the FDA granted avapritinib Breakthrough Therapy Designation for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation.

In July 2019, the European Medicines Agency validated Blueprint Medicines' Marketing Authorization Application for avapritinib in adult patients with PDGFRα D842V mutant GIST, regardless of prior therapy, and fourth-line GIST.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. Because currently available therapies primarily bind to the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.

In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. Mutational testing is critical to tailor therapy to the underlying disease driver and is recommended in expert guidelines. Currently, there are no approved therapies for patients with KIT-driven GIST whose disease progresses beyond imatinib, sunitinib and regorafenib. In patients with metastatic PDGFRα D842V-driven GIST, progression occurs in a median of approximately three to four months with available therapy.

https://pubchem.ncbi.nlm.nih.gov/compound/Avapritinib#section=2D-Structure

Eisai and Imbrium Therapeutics Announce U.S. FDA Filing Acceptance of New Drug Application for Lemborexant for the Treatment of Insomnia

In continuation of my update on lemborexant

Eisai Co., Ltd. (CEO: Haruo Naito, “Eisai”) and Imbrium Therapeutics L.P. (Imbrium Therapeutics), a clinical-stage biopharmaceutical company and operating subsidiary of Purdue Pharma, L.P. (President and CEO: Craig Landau, MD),  announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for lemborexant, an investigational agent being studied for the treatment of insomnia, a sleep-wake disorder. A Prescription Drug User Fee Act (PDUFA) date is set for December 27, 2019.

The NDA submission was based on data from the clinical development program including two pivotal Phase 3 studies of lemborexant – SUNRISE 1 (Study 304) and SUNRISE 2 (Study 303).

• SUNRISE 1: a one-month Phase 3 clinical study to evaluate the efficacy and safety of lemborexant versus placebo and versus an active comparator (zolpidem tartrate extended release, “zolpidem ER”) in 1,006 patients 55 years and older (45 percent of all patients were aged 65 years and older) with insomnia disorder. This study assessed sleep latency (using latency to persistent sleep; primary objective); sleep efficiency and wake after sleep onset (effect on maintaining sleep; key secondary objectives) objectively using polysomnography, and achieved its primary and key secondary objectives. The most common adverse events (AEs) reported in the lemborexant arms were headache and somnolence.1
• SUNRISE 2: a 12-month placebo-controlled (first six months) Phase 3 clinical study to evaluate the long-term efficacy and safety of lemborexant in 949 adult patients (18 to 88 years of age) with insomnia disorder. This study evaluated subjective (patient-reported) sleep onset latency (primary objective), sleep efficiency, and wake after sleep onset (key secondary objectives) using sleep diaries, and achieved its pre-specified primary and key secondary efficacy objectives. The most common AEs reported in the lemborexant arms were somnolence, nasopharyngitis, headache, and influenza.2

“Our ultimate goal for the development of a sleep-wake treatment is to bring to patients living with insomnia a new option that has the potential to improve their ability to fall asleep, stay asleep and wake the next morning without impairment,” said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. “This milestone for lemborexant brings us one step closer to addressing unmet needs for millions of patients who experience insomnia.”

“Insomnia, a disorder of sleep quality and quantity, causes significant impairment in daily functioning and has long-term consequences for health and well-being,”3 said John Renger, PhD, Vice President, Head of Research & Development and Regulatory Affairs, Imbrium Therapeutics. “We are committed to working with our partner Eisai to make this investigational treatment available to patients, pending regulatory approval.”

Lemborexant is being jointly developed by Eisai and Imbrium Therapeutics for the treatment of multiple sleep-wake disorders, including insomnia disorder. Information about ongoing clinical studies is available at clinicaltrials.gov.

Eisai and Imbrium Therapeutics are striving to address new unmet medical needs and to improve the lives of patients and their families.

This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.

About Lemborexant

Lemborexant is a novel investigational small molecule compound, discovered and developed by Eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2). In individuals with normal daily sleep-wake rhythms, orexin signaling is believed to promote periods of wakefulness. In individuals with sleep-wake disorders, it is possible that orexin signaling that regulates wakefulness is not functioning normally, suggesting that inhibiting inappropriate orexin signaling may enable initiation and maintenance of sleep. Eisai and Imbrium Therapeutics are investigating lemborexant as a potential treatment option for multiple sleep-wake disorders, such as insomnia. Additionally, a Phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder (ISWRD) and mild to moderate Alzheimer's dementia is underway.

About SUNRISE 1 (Study 304)

SUNRISE 1 was a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group study evaluating the efficacy and safety of lemborexant in 1,006 male or female adult patients 55 years and older (45 percent of patients were 65 years and older) with insomnia disorder conducted in North America and Europe. SUNRISE 1 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a 30-day treatment period and a minimum two-week period without treatment prior to the end-of-study visit. In this study, patients were randomized to receive placebo or one of three treatment regimens (lemborexant 5 mg, lemborexant 10 mg, zolpidem ER 6.25 mg).

The primary objective for SUNRISE 1 was to demonstrate using polysomnography that lemborexant at either the 5 mg or 10 mg dose is superior to placebo on objective sleep onset, as measured by latency to persistent sleep after the last two nights of one month of treatment. Key secondary objectives included change from baseline in sleep efficiency and wake after sleep onset (WASO) for both lemborexant doses compared to placebo, and WASO in the second half of the night (WASO2H) for both lemborexant doses compared to zolpidem ER, each after the last two nights of one month of treatment.

About SUNRISE 2 (Study 303)

SUNRISE 2 was a 12-month multicenter, global, randomized, controlled, double-blind, parallel-group study of the efficacy and safety of lemborexant in 949 male or female adult participants 18 to 88 years of age with insomnia disorder. SUNRISE 2 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a six-month placebo-controlled treatment period, a six-month period of active-only treatment and a two-week period without treatment prior to the end-of-study visit. In this study, during the placebo-controlled treatment period, patients were randomized to receive placebo or one of two treatment regimens (lemborexant 5 mg or 10 mg). During the active-only treatment period, patients who received placebo during the first period were re-randomized to receive lemborexant 5 mg or 10 mg. Patients who received active treatment during the first period continued on the treatment to which they were originally randomized.

The primary objective was change from baseline in subjective sleep onset latency after six months of placebo-controlled treatment using patient reported (subjective) sleep diaries. Key secondary endpoints were change from baseline in subjective sleep efficiency and subjective wake after sleep onset (sWASO) by using patient reported (subjective) sleep diaries for both lemborexant doses after six months of placebo-controlled treatment.

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

Eisai and Imbrium Therapeutics Announce U.S. FDA Filing Acceptance of New Drug Application for Lemborexant for the Treatment of Insomnia