Zevra Therapeutics Announces Resubmission of Arimoclomol New Drug Application to the U.S. Food and Drug Administration

Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) a rare disease therapeutics company, today announced it resubmitted its New Drug Application (NDA) for arimoclomol, an investigational therapeutic candidate for the treatment of Niemann-Pick disease type C (NPC) to the U.S. Food and Drug Administration (FDA) on December 22, 2023. Based on standard NDA resubmission review timelines, an acknowledgment letter from the FDA that the resubmission is complete and setting the PDUFA date is expected within 30 days. Zevra expects the NDA to be classified as a Class II submission which would be subject to a review period by the FDA within six months from the date of submission.

“The Zevra team has worked diligently to deliver a high quality and thorough resubmission of the NDA for arimoclomol following multiple interactions with the FDA and after incorporating direction from the agency,” said Neil McFarlane, President and Chief Executive Officer of Zevra. “We continue to accelerate our launch preparations in anticipation of FDA approval, and believe we are one step closer to getting arimoclomol into the hands of patients who are seeking a treatment.”

“Zevra has engaged with the advocacy community, elevating the patient voice throughout arimoclomol’s development process,” said Daniel Gallo, Ph.D., Zevra’s Senior Vice President of Medical Affairs and Advocacy. “The advocacy community’s input has been instrumental in building awareness of the need for approved treatments that address the unmet needs of individuals and their caregivers living with this debilitating condition.”

Zevra believes it has addressed the issues previously raised by the FDA in the complete response letter by providing additional evidence to support the use of the Niemann-Pick type C Clinical Severity Scale (NPCCSS) and, conducting additional studies used to support the potential mechanism of action. Additionally, new data included in the resubmission comes from multiple non-clinical studies, natural history comparisons, real-world data generated from the ongoing early access programs in the United States and the European Union, as well as data from the four-year open-label extension of the Phase 2/3 clinical trial (NCT02612129). Results from this open-label trial suggest that arimoclomol reduces the long-term progression of NPC.

Arimoclomol has been evaluated in a total of 21 studies across a range of Phase 1, 2 or 3 clinical trials evaluating its safety and efficacy across more than 600 subjects in NPC, other disease or healthy subjects. The primary efficacy trial evaluating arimoclomol for the treatment of NPC was a Phase 2/3 double-blind, placebo-controlled trial (CT-ORZY-NPC-002) of arimoclomol in 50 patients with NPC.

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

Zevra Therapeutics Announces Resubmission of Arimoclomol New Drug Application to the U.S. Food and Drug Administration

Zealand Pharma Submits New Drug Application to the US FDA for Glepaglutide in Short Bowel Syndrome

Zealand Pharma A/S  announced the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for glepaglutide, a long-acting GLP-2 analog, for the treatment of adult patients with short bowel syndrome (SBS) dependent on parenteral support.

“Short bowel syndrome with intestinal failure is a complex, chronic and severe condition in which individuals are dependent on receiving fluids and nutrition parenterally. While life-sustaining, parenteral support poses significant restrictions on daily life and carries a risk of serious and life-threatening complications. More effective and convenient treatments to further reduce parenteral support are needed, with the ultimate goal of discontinuing parenteral support and achieving enteral autonomy,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “We believe glepaglutide, once approved, can reduce both the burden of parenteral support and of daily dosing of existing GLP-2 treatment for people living with SBS and intestinal failure, and we are pleased to submit this treatment for regulatory review and potential approval in the US.”

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

Zealand Pharma Submits New Drug Application to the US FDA for Glepaglutide in Short Bowel Syndrome

Journey Medical Corporation Submits New Drug Application to FDA for DFD-29 to Treat Rosacea

Journey Medical Corporation,  announced that the Company has submitted,  a New Drug Application (“NDA”) to the FDA seeking approval for DFD-29 (Minocycline Hydrochloride Modified Release Capsules, 40 mg) for the treatment of inflammatory lesions and erythema of rosacea in adults. DFD-29 is being developed in collaboration with Dr. Reddy’s Laboratories Ltd.

“This NDA submission is a significant milestone for Journey Medical and we look forward to collaborating with the FDA during its review to bring DFD-29, a potentially differentiated, best-in-class oral rosacea treatment, one step closer to patients. Based on the data seen in our pivotal trials, DFD-29 could fundamentally improve the treatment paradigm for patients suffering from both inflammatory lesions and erythema (redness) from rosacea,” said Claude Maraoui, Co-Founder, President and Chief Executive Officer of Journey Medical.

The NDA submission is supported by positive data from Journey Medical’s two DFD-29 Phase 3 clinical trials for the treatment of rosacea. The Phase 3 clinical trials achieved all co-primary and secondary endpoints, and subjects completed the 16-week treatment with no significant safety issues. DFD-29 demonstrated statistical superiority over both the current standard-of-care treatment, Oracea® 40 mg capsules, and placebo for Investigator’s Global Assessment treatment success as well as the reduction in the total inflammatory lesion count in both studies. On a secondary endpoint related to erythema (redness) assessment, DFD-29 showed statistically significant reduction in Clinician’s Erythema Assessment (CEA) compared to placebo in both clinical trials.

Rosacea, which affects approximately 16 million people in the United States according to the National Rosacea Society, is a long-term, inflammatory skin condition that causes small, red, pus-filled bumps, redness and visible blood vessels in the face. DFD-29 has the potential to become the only oral, systemic therapy to address both inflammatory lesions and erythema (redness) from rosacea, as demonstrated in the clinical trials.

Ref : https://en.wikipedia.org/wiki/Minocycline

Journey Medical Corporation Submits New Drug Application to FDA for DFD-29 to Treat Rosacea

Amneal Announces Complete Response Resubmission for IPX203 New Drug Application

Amneal Pharmaceuticals, Inc. (NASDAQ: AMRX) (“Amneal” or the “Company”) today announced that it has provided a Complete Response resubmission to the U.S. Food and Drug Administration (FDA) for IPX203, a novel, oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules for the treatment of Parkinson’s disease (PD).

Carbidopa

levodopa 

The original NDA for IPX203 resulted in a Complete Response Letter (CRL) from FDA. The resubmission package included data from a healthy volunteer study which was conducted in the fourth quarter of 2023. The FDA did not request any other studies.

“We are pleased to provide our complete response resubmission for IPX203 as we look to expand our Parkinson’s franchise,” said Chirag and Chintu Patel, Co-Chief Executive Officers at Amneal. “We look forward to launching this much-needed treatment in the second half of 2024, subject to FDA approval.”

About IPX203 

IPX203 is a novel, oral formulation of CD/LD extended-release capsules designed for the treatment of Parkinson’s disease. IPX203 contains immediate-release granules and extended-release coated beads. The IR granules consist of CD and LD, with a disintegrant polymer to allow for rapid dissolution. The ER beads consist of LD, coated with a sustained release polymer to allow for slow release of the drug a mucoadhesive polymer to keep the granules adhered to the area of absorption longer, and an enteric coating to prevent the granules from disintegrating prematurely in the stomach. This formulation is distinct from RYTARY® (carbidopa/levodopa) extended-release capsules, Amneal’s extended-release CD/LD treatment for PD approved by the U.S. FDA in 2015.

About Parkinson’s Disease

Parkinson’s disease has become the fastest growing neurological disorder worldwide, with approximately 1 million patients diagnosed in the U.S. It is a progressive disorder of the central nervous system (CNS) that affects dopamine-producing neurons in the brain that affect movement.

PD is characterized by slowness of movement, stiffness, resting tremor and impaired balance.  While PD is not considered a fatal disease, it is associated with significant morbidity and disability.  The average age at diagnosis for patients with PD is 60; as people live longer, the number of patients living with PD is predicted to grow significantly over the coming decades. 

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

https://en.wikipedia.org/wiki/L-DOPA

Amneal Announces Complete Response Resubmission for IPX203 New Drug Application

Defender Pharmaceuticals Receives Complete Response Letter from the U.S. Food and Drug Administration for its Intranasal Scopolamine (DPI-386) New Drug Application for the Prevention of Nausea and Vomiting Induced by Motion in Adults

Defender Pharmaceuticals, Inc. (the “Company” or “Defender”), a privately held life sciences company based in St. Louis, today announced the issuing of a Complete Response Letter (CRL) , by the U.S. Food and Drug Administration (FDA) to the Company’s New Drug Application (NDA) for intranasal scopolamine (DPI-386) for the prevention of nausea and vomiting induced by motion in adults.

“Following our review of the CRL, we plan on scheduling a formal meeting with the FDA to fully understand the issues raised in the CRL so we can develop and implement a comprehensive action plan,” said Barry I. Feinberg, M.D., President & CEO of Defender Pharmaceuticals. “We remain confident that our intranasal scopolamine is a safe and effective therapy for the prevention of motion sickness, and we will work closely with the FDA to ensure that we can bring this innovative new product to the market.”

About intranasal scopolamine (DPI-386) Development Program

Defender has worked with the United States Naval Medical Research Unit (NAMRU-D) and the National Aeronautics and Space Administration (NASA) on its intranasal scopolamine development program that is focused on specific military personnel and astronauts.

To date, more than 1,300 patients have participated in Defender clinical studies, including over 500 participants in the DPI-386-MS-33 study. Given the successful outcome of DPI-386-MS-33, Defender has submitted a New Drug Application (NDA) to the Food and Drug Administration (FDA) for DPI-386 Nasal Gel for the prevention of nausea and vomiting induced by motion in adults.

Defender is also developing intranasal formulations designed to treat a wide variety of indications. We believe these new products have the potential to help safeguard health across civilian and military populations.

About Motion-Related Discomfort
Certain motions cause discomfort in individuals while engaged in various leisure or travel-related activities. Most forms of travel, whether on land, in the air, or on the water, can trigger symptoms such as nausea and vomiting (example: flying, boating/fishing, car, bus, and train). Symptoms induced by motion can also have a detrimental impact on the ability of various military personnel and astronauts to perform assigned duties, potentially impacting readiness and negatively impacting resources. Motion-related discomfort is a common and transient response to unfamiliar or unnatural motion or contradictory spatial sensory information, resulting in decrements to performance of tasks, pallor, cold sweating, nausea and vomiting. Prolonged exposure to certain motions may induce sopite-related symptoms such as loss of drive and concentration, drowsiness, sleepiness, apathy, depression, and a feeling of impending doom.

Ref : https://en.wikipedia.org/wiki/Scopolamine

Defender Pharmaceuticals Receives Complete Response Letter from the U.S. Food and Drug Administration for its Intranasal Scopolamine (DPI-386) New Drug Application for the Prevention of Nausea and Vomiting Induced by Motion in Adults

Lykos Therapeutics Announces FDA Acceptance and Priority Review of New Drug Application for MDMA-Assisted Therapy for PTSD

Lykos Therapeutics (formerly MAPS Public Benefit Corporation) ("Lykos"), a company dedicated to transforming mental healthcare, announced that the U.S. Food and Drug Administration ("FDA") has accepted its new drug application ("NDA") for midomafetamine capsules ("MDMA") used in combination with psychological intervention, which includes psychotherapy (talk therapy) and other supportive services provided by a qualified healthcare provider for individuals with post-traumatic stress disorder ("PTSD"). The FDA has granted the application priority review and has assigned a Prescription Drug User Fee Act ("PDUFA") target action date of August 11, 2024. If approved, this would be the first MDMA-assisted therapy and psychedelic-assisted therapy.

"Securing priority review for our investigational MDMA-assisted therapy is a significant accomplishment and underscores the urgent unmet need for new innovation in the treatment of PTSD," said Amy Emerson, chief executive officer of Lykos Therapeutics. "We remain focused on working with the FDA through the review process and preparing for a controlled launch with an emphasis on quality should this potential treatment be approved."

The NDA submission included results from numerous studies including two randomized, double-blind, placebo-controlled Phase 3 studies (MAPP1 and MAPP2) evaluating the efficacy and safety of MDMA used in combination with psychological intervention versus placebo with therapy in participants diagnosed with severe or moderate to severe PTSD, respectively. Both MAPP1 and MAPP2 studies met their primary and secondary endpoints and were published in Nature Medicine. 1, 2 The primary endpoint for both studies was to assess changes in PTSD symptom severity as measured by the change from baseline in Clinician-Administered PTSD Scale for DSM-5 ("CAPS-5"). The key secondary endpoint of both studies was to assess improvement in functional impairment associated with PTSD as measured by the change from baseline in the Sheehan Disability Scale ("SDS"). No serious adverse events were reported in the MDMA group in either study.

The FDA grants priority review for drugs that, if approved, would represent significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. 

MDMA-assisted therapy has not been approved by any regulatory agency. The safety and efficacy of MDMA-assisted therapy has not been established for the treatment of PTSD. Investigational MDMA-assisted therapy is also being studied in other indications.

About MDMA-Assisted Therapy

MDMA (3,4-methylenedioxymethamphetamine) is not new to mental health professionals. MDMA is an entactogen— a class of psychoactive compounds that are differentiated from classic psychedelics (i.e., psilocybin, mescaline and LSD) and are defined based on their mechanism and known effects of increasing self-awareness leading to introspection and personal reflection.27,,28 In the 1970's and early 1980's MDMA was used in conjunction with talk therapy by mental health providers to enhance patients' access, processing, and communication of difficult emotions and experiences.29 In 1985, the U.S. Drug Enforcement Administration ("DEA") made MDMA a Schedule I drug under the Controlled Substances Act preventing it from being used for recreational or medical use. 30 Since then, research has shown the unique properties of MDMA allow it to act as a powerful catalyst to support psychotherapy by helping diminish the brain's fear response allowing people to access and process painful memories without being overwhelmed. 31 However, additional clinical trials would be needed to secure regulatory review and potential approval.

Lykos, with longstanding roots in advocacy for psychedelic medicine, pioneered the first randomized, double-blind, placebo controlled clinical trials evaluating the efficacy and safety of MDMA-assisted therapy as an investigational modality using midomafetamine (MDMA) in combination with psychological intervention to treat PTSD.

With a growing body of evidence supporting the potential medical use of MDMA, in 2017 the FDA granted the company's investigational MDMA-assisted therapy Breakthrough Therapy designation, a process designed to expedite the development and review of drugs intended to treat serious conditions for which preliminary scientific evidence indicates that it may demonstrate a substantial improvement over available therapies. If approved by the FDA, the U.S. Drug Enforcement Administration ("DEA") would be required to reschedule MDMA making it available for prescription medical use.

Ref: https://en.wikipedia.org/wiki/MDMA

Lykos Therapeutics Announces FDA Acceptance and Priority Review of New Drug Application for MDMA-Assisted Therapy for PTSD

Liquidia Corporation Provides Update on New Drug Application for Yutrepia (treprostinil) inhalation powder

Liquidia Corporation (the Company) (NASDAQ: LQDA) announced  the U.S. Food and Drug Administration (FDA) providing  an update on its review of the New Drug Application (NDA) for Yutrepia™ (treprostinil) inhalation powder to treat pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). The FDA informed the Company that it is confirming the process for adding the PH-ILD indication as an amendment to the NDA for Yutrepia. Accordingly, the FDA is not able to issue an action letter in time to meet the previously issued Prescription Drug User Fee Act (PDUFA) goal date of January 24, 2024, and their review remains ongoing. The FDA did not request any additional clinical data to support the NDA and did not issue a new PDUFA goal date.

Dr. Roger Jeffs, Chief Executive Officer, said: “We are in active communication with the FDA regarding the process we followed to amend our NDA to add PH-ILD to the labeled indication. Whether the NDA is amended or supplemented, we will continue to prepare for the final FDA approval of Yutrepia to treat both PAH and PH-ILD patients following the expiration of regulatory exclusivity for Tyvaso® on March 31, 2024. As communicated by the tentative approval to treat PAH, Yutrepia has already met the regulatory standards for quality, safety and efficacy. We remain committed to addressing the unmet needs across all patients whose lives may be improved by the unique benefits of Yutrepia.”

On November 5, 2021, the FDA issued a tentative approval for Yutrepia for the treatment of PAH to improve exercise ability in adult patients with New York Heart Association (NYHA) Functional Class II-III symptoms. In July 2023, Liquidia filed an amendment to its New Drug Application for Yutrepia, seeking to add PH-ILD to the label. The FDA previously confirmed that Yutrepia may include the treatment of PH-ILD to the proposed label for Yutrepia without additional clinical studies.

Yutrepia also remains subject to ongoing litigation. Liquidia filed a request for Judge Andrews of the U.S. District Court for the District of Delaware (District Court) to set aside the injunction that was instituted in August 2022 tied to litigation filed by United Therapeutics (UTHR) alleging patent infringement of U.S. Patent No. 10,716,793 (the ‘793 Patent) in Case No. 1:20-cv-00755-RGA (the Original Hatch-Waxman Litigation). On December 20, 2023, the United States Court of Appeals for the Federal Circuit (CAFC) affirmed the earlier decision by the Patent Trial and Appeal Board (PTAB), which found all claims of the ‘793 Patent to be unpatentable due to the existence of prior art cited by Liquidia in inter partes review proceedings.

Additionally, in September 2023, UTHR filed a second complaint for patent infringement in District Court in Case No. 1:23-cv-00975-RGA (the New Hatch-Waxman Litigation). As of January 22, 2024, the only patent at issue is U.S. Patent No. 11,826,327 (the ‘327 Patent) which issued November 30, 2023. UTHR has stipulated to the dismissal of the ‘793 Patent from the New Hatch-Waxman Litigation as a result of the CAFC decision affirming invalidity of the '793 Patent. The ’327 Patent, the sole remaining patent at issue in the New Hatch-Waxman Litigation, was not issued before Liquidia submitted the NDA for Yutrepia in January 2020 to treat PAH. Therefore, the Company believes that final FDA approval for Yutrepia will not be subject to any statutory 30-month stay arising from the New Hatch-Waxman Litigation per Section 505(c)(3)(C) of the Federal Food, Drug and Cosmetic Act.

Ref: https://en.wikipedia.org/wiki/Treprostinil

Read https://www.drugs.com/nda/yutrepia_240125.html

Liquidia Corporation Provides Update on New Drug Application for Yutrepia (treprostinil) inhalation powder

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