FDA Approval to Expand the Age Range for Ravicti (glycerol phenylbutyrate) Oral Liquid to Include Newborns

  In  continuation of my update on   glycerol phenyl butyrate   

        Horizon Pharma plc (NASDAQ: HZNP) announced the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) to expand the age range for Ravicti (glycerol phenylbutyrate) Oral Liquid to include infants younger than two months of age living with a urea cycle disorder (UCD).

Ravicti is now FDA-approved for use as a nitrogen-binding agent for chronic management of UCDs in adults and children of all ages who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Ravicti must be used with dietary protein restriction and, in some cases, dietary supplements. Ravicti is not indicated for treatment of acute hyperammonemia in patients with UCDs, and its safety and efficacy for the treatment of n-acetylglutamate synthase (NAGS) deficiency has not been established.

“The FDA approval of Ravicti for children younger than two months provides a new alternative for the management of patients with a UCD that is easy to dose and administer to infants given the liquid formulation,” said Nicola Longo, M.D., Ph.D., clinical geneticist at Primary Children’s Hospital and the University of Utah Hospital, and a lead investigator of a clinical study evaluating Ravicti for newborns. “UCDs are severe and can be life-threatening. We hope that the combination of early diagnosis – through newborn screening or by measurement of ammonia levels – and the availability of novel treatments, such as this one, can help to improve the outcome of affected patients.”

A study was conducted to assess safety, efficacy and pharmacokinetics in pediatric patients with UCDs two months of age and younger (n=16). In the study, 10 patients transitioned to Ravicti from sodium phenylbutyrate, three transitioned from intravenous sodium benzoate and sodium phenylacetate, and three were treatment naïve. Patients were treated with Ravicti for an average of 10.7 months. Results demonstrated safety and efficacy in children younger than two months, with Ravicti-treated patients maintaining stable ammonia levels relative to their pre-study enrollment. In addition, mean ammonia levels were lower during treatment with Ravicti compared to baseline values.

“As we increase our efforts to develop new investigational medicines for people living with rare and rheumatic diseases, Horizon continues to seek ways to better serve patients with our current medicines,” said Elizabeth Thompson, Ph.D., vice president, clinical development, rare diseases, Horizon Pharma. “The FDA approval of Ravicti for children under the age of two months is a milestone in our efforts to help people living with UCDs, and we are proud to be bringing a new treatment option to the vulnerable newborn patient population.”

A UCD is a rare genetic disorder that affects approximately 1 in 35,000 live births in the United States. It is caused by an enzyme deficiency in the urea cycle, a process that is responsible for converting excess ammonia from the bloodstream and ultimately removing it from the body. Because of this, people with a UCD experience hyperammonemia, or elevated ammonia levels in their blood, that can then reach the brain and cause irreversible brain damage, coma or death. UCD symptoms may first occur at any age depending on the severity of the disorder, with more severe defects presenting earlier in life. 

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Horizon Pharma plc Announces FDA Approval to Expand the Age Range for Ravicti (glycerol phenylbutyrate) Oral Liquid to Include Newborns

Phenylbutyrate for treating Alzheimer's Disease !...

We know that Phenylbutyrate is adrug, used to prescribe for patients suffering from alterations in the urea cycle. Now, Ana García-Osta and co-workers have come up with something interseting, sodium phenyl butyrate can be used to treat Alzheimer disease.

Alzheimer's disease is a neurodegenerative disorder associated with age and characterized by the progressive deterioration of cognitive and intellectual abilities. "Cognitive deficit is associated with a loss of neuron connections. For the memory to develop, it is necessary for a series of cellular and molecular mechanisms to be activated. The interruption of these processes affects the capacity to assimilate and store new memories. Since this a drug already established for its toxicity, if the results claimed by Dr. Ana are established and the mechanism of action are studied, hope this research will add one more drug as serendipity and also the much needed help for those sufferings...

FDA Approves Relyvrio (sodium phenylbutyrate/taurursodiol) for Patients with Amyotrophic Lateral Sclerosis (ALS)

In continuation of my update on phenyl butyrate and taurursodiol..

Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”)   announced  the U.S. Food and Drug Administration (FDA)   approval of Relyvrio (sodium phenylbutyrate and taurursodiol) for the treatment of adults with amyotrophic lateral sclerosis (ALS). Relyvrio (previously known as AMX0035 in the U.S.) significantly slowed the loss of physical function in people living with ALS in a randomized, placebo-controlled clinical trial. Relyvrio can be taken as a monotherapy or with existing approved treatments.

“Today’s FDA approval of Relyvrio is an exciting milestone for the ALS community and is a major step toward achieving our mission to one day end the suffering caused by neurodegenerative diseases,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx. “We want to give a heartfelt thank you to the broader ALS community, including healthcare professionals and those living with ALS, for their guidance, support of our clinical programs, and for sharing their experiences with us. Their stories inspired us and helped our team to better understand the ALS clock, instilling in us a deep sense of urgency that will continue to drive us forward. This is just the beginning and there is much more to be done.”
ALS is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis and eventually, death. More than 90% of people with ALS have sporadic disease, showing no clear family history. ALS affects approximately 29,000 people in the U.S.

Leading U.S. ALS advocacy organizations including The ALS Association, Answer ALS Foundation, I AM ALS, Les Turner ALS Foundation and Team Gleason said in a statement, “Our organizations have been on a mission to create a world free of ALS. With today’s approval, we are encouraged that Relyvrio can offer people living with ALS and their families the potential of more time with functional independence. This is especially important for a rapidly progressive disease with a median survival time from diagnosis of just two to three years. This is significant for people living with ALS, their loved ones, caregivers, clinicians, researchers, and advocacy, as we now have a new treatment option that could be a big step forward for the future of ALS care.”

The approval of Relyvrio is based on data from CENTAUR, a multicenter Phase 2 clinical trial in 137 participants with ALS encompassing a 6-month randomized, placebo-controlled phase and an open-label extension (OLE) long-term follow-up phase. Detailed data from CENTAUR were published in the New England Journal of Medicine, Muscle & Nerve, and the Journal of Neurology, Neurosurgery, and Psychiatry.

The most common adverse events occurring with Relyvrio (at least 15% and at least 5% greater than placebo) were diarrhea, abdominal pain, nausea, and upper respiratory tract infection. Gastrointestinal-related adverse reactions occurred throughout the study but were more frequent during the first three weeks of treatment.

“Any time we have a new tool to slow the progression of this disease represents an important milestone in how we battle ALS. The published data on both function and survival in a randomized trial – and what this means for people living with ALS – are a step forward for the ALS community,” said Sabrina Paganoni, M.D., Ph.D., principal investigator of the CENTAUR trial, investigator at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, and Associate Professor of Physical Medicine and Rehabilitation at Harvard Medical School and Spaulding Rehabilitation Hospital.

FDA Approves Relyvrio (sodium phenylbutyrate/taurursodiol) for Patients with Amyotrophic Lateral Sclerosis (ALS)

FDA Approves Olpruva (sodium phenylbutyrate) for Patients with Urea Cycle Disorders

In continuation of my update on Phenyl butyrate 

Acer Therapeutics Inc. and its collaboration partner, RELIEF THERAPEUTICS Holding SA (“Relief”),  announced the U.S. Food and Drug Administration (FDA)  approval Olpruva™ (sodium phenylbutyrate) of  oral suspension in the U.S. for the treatment of certain patients living with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS).

“The FDA’s approval of Olpruva, an innovative formulation of sodium phenylbutyrate packaged for the first time in single-dose envelopes, marks the culmination of our ongoing dedication to develop new and differentiated treatment options for those affected by rare diseases,” said Chris Schelling, chief executive officer and founder of Acer. “Patients who are living with UCDs now have an alternative treatment option with Olpruva™, to address some of the challenges they may have with existing therapy. We are pleased to be able to provide a new, approved treatment choice for those living with this challenging disease.”

Mr. Schelling continued, “This approval represents the first FDA-approved product for Acer, validating our ability to identify and develop treatments where science can be applied in novel ways and make them available to patients as quickly and efficiently as possible. In addition, this approval unlocks our Marathon debt funding option and provides us with resources to advance our pipeline of investigational product candidates.”

“The daily challenges of living with a UCD can be overwhelming and emotionally draining for patients and their families,” said Tresa Warner, president of the National Urea Cycle Disorders Foundation. “We welcome new treatment options that can help patients, caregivers and their healthcare teams manage UCDs.”

Olpruva’s™ approval triggers the availability of a $42.5 million term loan to Acer under the previously announced March 2022 loan agreement the Company entered into with affiliates of Marathon Asset Management L.P. If Acer requests and receives the loan proceeds, management believes it will have sufficient resources to fund current operations into H2 2023.

Olpruva™ has been approved as an oral suspension by the FDA for the treatment of patients with UCDs. UCDs are a group of rare, genetic disorders that can cause harmful ammonia to build up in the blood, potentially resulting in brain damage and neurocognitive impairments, if ammonia levels are not controlled.1 Any increase in ammonia over time is serious. Therefore, it is important to adhere to any dietary protein restrictions and have alternative medication options to help control ammonia levels.

“This FDA approval is a significant milestone for patients with UCDs in the U.S., offering an additional choice to manage their condition,” added Jack Weinstein, chief executive officer of Relief. “We look forward to building on Olpruva™’s approval in the U.S. and expanding its availability into other territories outside of the U.S.”

Olpruva™ received FDA approval under section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (FDCA), a regulatory pathway that allows applicants to rely, at least in part, on third party data for approval. In its New Drug Application (NDA), Acer cited preclinical and clinical safety and efficacy data from the reference listed drug (RLD), BUPHENYL® powder, which is approved as adjunctive therapy in the chronic management of patients with UCDs involving deficiencies of CPS, OTC or AS. In its NDA, Acer also provided additional data including studies that evaluated the bioavailability and bioequivalence of Olpruva™ compared to BUPHENYL® powder. The data from these studies, presented at the Society for Inherited Metabolic Disorders (SIMD) Annual Meeting in April 2022 and the Genetic Metabolic Dieticians International (GMDI) Conference in May 2022, showed that Olpruva™ was bioequivalent to BUPHENYL® powder.

Commitment to Patient Access

Acer intends to offer Navigator by Acer Therapeutics, a suite of integrated patient support services designed to facilitate access to therapy. Navigator by Acer Therapeutics is designed to assist UCD patients with support, access, education, and adherence.

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