FDA Approves Zycubo (copper histidinate) for Children With Menkes Disease

Sentynl Therapeutics Inc. (“Sentynl”), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences Limited (“Zydus Group”), announced that the U.S. Food and Drug Administration (“FDA”) has approved Zycubo® (copper histidinate) for the treatment of Menkes disease in pediatric patients. This is the first and only treatment approved for Menkes disease, a rare and fatal genetic condition, in the United States. Zycubo® is not indicated for the treatment of Occipital Horn Syndrome.

“Approval is a pivotal step towards achieving our goal of making a meaningful impact on patients, caregivers, and the rare disease community,” said Dr. Sharvil P. Patel, Managing Director, Zydus Lifesciences Limited. “This milestone marks a transformative moment for the Zydus Group and for families affected by Menkes disease. For the first time, patients have access to an approved therapy, offering hope where no options existed. We are proud to advance patient care and deliver innovative solutions to those who need them most.”

Menkes disease is a rare X-linked recessive pediatric disease caused by mutations of the copper transporter ATP7A encoded by the ATP7A gene. Patients with Menkes disease are born with the inability to absorb dietary copper and subsequently have impaired copper transport across the blood-brain barrier, and, until now, there has been no approved treatment in the United States. Zycubo® is a subcutaneous injectable formulation of copper histidinate that restores copper homeostasis and maintains copper levels in patients with Menkes disease.

“Menkes disease presents significant challenges for patients and their families. With no known cure, most untreated patients do not survive beyond three years of age,” said Matt Heck, CEO, Sentynl. “FDA’s approval serves as compelling affirmation that a safe and effective therapy is now available for patients living with this devastating disease.”

The approval is supported by positive topline clinical efficacy results for Zycubo, demonstrating statistically significant improvement in overall survival for Menkes disease subjects who received early treatment (“ET”) with Zycubo, compared to an untreated contemporaneous external control cohort, with a nearly 80% reduction in the risk of death. Median overall survival (“OS”) was 177.1 months for Zycubo ET cohort compared to 17.6 months for the untreated contemporaneous external control cohort.

The most common adverse reactions (incidence ≥7%) were pneumonia, viral infection, respiratory failure, seizure, bacterial infection, hemorrhage, hypotension, vomiting, tachycardia, pyrexia, volume depletion, fracture, dyspnea, transaminases elevation, diarrhea, fungal infection, anemia, and local administration reaction.

“This milestone represents the culmination of decades of research into better understanding and ultimately finding an effective treatment for Menkes disease,” said Dr. Stephen Kaler, a clinical genetics and genomics specialist at the Columbia University Medical Center. “Increased awareness of Menkes disease and rapid testing upon suspicion are critical, as beginning copper histidinate therapy in affected neonates has been shown to reduce symptoms and prolong life.”

Acquired from Cyprium Therapeutics in 2023, Sentynl has advanced Zycubo through the final stages of development with the FDA based on positive results from pivotal studies, receiving Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and the FDA Orphan Drug Designations. Copper histidinate has also been granted Orphan Designation by the European Medicines Agency.

ttps://upload.wikimedia.org/wikipedia/commons/thumb/a/ae/Copper_histidinate_v2.svg/250px-Copper_histidinate_v2.svg.png

FDA Approves Zycubo (copper histidinate) for Children With Menkes Disease

FDA Approves Zycubo (copper histidinate) for Children With Menkes Disease

Sentynl Therapeutics Inc. (“Sentynl”), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences Limited (“Zydus Group”), announced that the U.S. Food and Drug Administration (“FDA”) has approved Zycubo® (copper histidinate) for the treatment of Menkes disease in pediatric patients. This is the first and only treatment approved for Menkes disease, a rare and fatal genetic condition, in the United States. Zycubo® is not indicated for the treatment of Occipital Horn Syndrome.

“Approval is a pivotal step towards achieving our goal of making a meaningful impact on patients, caregivers, and the rare disease community,” said Dr. Sharvil P. Patel, Managing Director, Zydus Lifesciences Limited. “This milestone marks a transformative moment for the Zydus Group and for families affected by Menkes disease. For the first time, patients have access to an approved therapy, offering hope where no options existed. We are proud to advance patient care and deliver innovative solutions to those who need them most.”

Menkes disease is a rare X-linked recessive pediatric disease caused by mutations of the copper transporter ATP7A encoded by the ATP7A gene. Patients with Menkes disease are born with the inability to absorb dietary copper and subsequently have impaired copper transport across the blood-brain barrier, and, until now, there has been no approved treatment in the United States. Zycubo® is a subcutaneous injectable formulation of copper histidinate that restores copper homeostasis and maintains copper levels in patients with Menkes disease.

“Menkes disease presents significant challenges for patients and their families. With no known cure, most untreated patients do not survive beyond three years of age,” said Matt Heck, CEO, Sentynl. “FDA’s approval serves as compelling affirmation that a safe and effective therapy is now available for patients living with this devastating disease.”

The approval is supported by positive topline clinical efficacy results for Zycubo, demonstrating statistically significant improvement in overall survival for Menkes disease subjects who received early treatment (“ET”) with Zycubo, compared to an untreated contemporaneous external control cohort, with a nearly 80% reduction in the risk of death. Median overall survival (“OS”) was 177.1 months for Zycubo ET cohort compared to 17.6 months for the untreated contemporaneous external control cohort.

The most common adverse reactions (incidence ≥7%) were pneumonia, viral infection, respiratory failure, seizure, bacterial infection, hemorrhage, hypotension, vomiting, tachycardia, pyrexia, volume depletion, fracture, dyspnea, transaminases elevation, diarrhea, fungal infection, anemia, and local administration reaction.

“This milestone represents the culmination of decades of research into better understanding and ultimately finding an effective treatment for Menkes disease,” said Dr. Stephen Kaler, a clinical genetics and genomics specialist at the Columbia University Medical Center. “Increased awareness of Menkes disease and rapid testing upon suspicion are critical, as beginning copper histidinate therapy in affected neonates has been shown to reduce symptoms and prolong life.”

Acquired from Cyprium Therapeutics in 2023, Sentynl has advanced Zycubo through the final stages of development with the FDA based on positive results from pivotal studies, receiving Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and the FDA Orphan Drug Designations. Copper histidinate has also been granted Orphan Designation by the European Medicines Agency.

FDA Approves Zycubo (copper histidinate) for Children With Menkes Disease

FDA Approves Linzess (linaclotide) for Children 7 Years and Older with Irritable Bowel Syndrome with Constipation

The U.S. Food and Drug Administration (FDA) has approved Linzess (linaclotide) capsules for pediatric patients 7 years and older with irritable bowel syndrome with constipation (IBS-C). Linzess is the first treatment approved for IBS-C in pediatric patients.

Disease or Conditions

IBS-C is a common condition affecting children and adolescents characterized by chronic constipation (which occurs when patients have infrequent bowel movements with hard stools that may be difficult or painful to pass), abdominal pain, and bloating. There is no known underlying organic cause and there are typically multiple contributing factors.

Efficacy

The effectiveness of Linzess to treat IBS-C was established in pediatric patients 7 years and older. Linzess for this indication was supported by extrapolation of efficacy from adequate and well-controlled studies in adults and a 12-week double-blind, randomized, parallel-group trial in pediatric patients 7 to 17 years who met modified Rome III criteria for child/adolescent IBS-C. The primary endpoint was the proportion of patients who achieved at least a 30% reduction in abdominal pain and an increase of at least two spontaneous (i.e., naturally occurring) bowel movements per week from baseline for at least 6 weeks of the 12-week treatment period. The efficacy results were consistent with results demonstrated in the adult IBS-C population.

Safety

The safety of Linzess in these clinical studies was similar in adult and pediatric patients. The most common side effect reported in pediatric patients 7 to 17 years with IBS-C was diarrhea. If severe diarrhea occurs, patients should discontinue Linzess and be rehydrated. Patients younger than 2 years can be at risk of serious dehydration and should not take Linzess for any indication, nor should patients with known or suspected mechanical gastrointestinal obstruction (bowel blockage). See the full prescribing information for additional information on risks associated with Linzess.

The recommended dosage for pediatric patients 7 years and older with IBS-C is 145 mcg orally once daily.

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

FDA Approves Linzess (linaclotide) for Children 7 Years and Older with Irritable Bowel Syndrome with Constipation

FDA Approves Lampit (nifurtimox) for the Treatment of Chagas Disease in Children

Bayer announced  that  the United States Food and Drug Administration (FDA) has approved Lampit (nifurtimox) for use in pediatric patients (from birth to less than 18 years of age and weighing at least 2.5 kg) for the treatment of Chagas disease (American Trypanosomiasis) caused by Trypanosoma cruzi (T. cruzi).1 Lampit, an antiprotozoal medication will be available in a new, dividable tablet that can be split on the scored lines by hand.1-3 According to prescribing instructions, the tablet is specially formulated to disperse in water, which can aid in the dosing and administration to pediatric patients who may have difficulty swallowing whole or half tablets. 

This indication is approved under accelerated approval based on the number of treated patients who became immunoglobulin G (IgG) antibody negative or who showed an at least 20% decrease in optical density on two different IgG antibody tests against antigens of T. cruzi. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Chagas is an infectious tropical disease that affects an estimated 300,000 people in the U.S.4 The disease is endemic throughout much of Latin America, though it is a growing health concern in the U.S.5,6 Approval of a treatment for pediatric patients is an important milestone.

“Chagas disease can strike at any age, and early detection and treatment are important. This is especially relevant for children,” said Aleksandra Vlajnic, MD, senior vice president and head of Medical Affairs for the Americas at Bayer. “The importance of treating children is a major reason behind Bayer’s collaboration with health authorities to enhance access to Lampit as a means to provide treatment for Chagas disease.”

The FDA approval is based on results from the Chagas disease in children treated with nifurtimoxstudy, the first part of the largest Phase III program ever conducted in pediatric patients for the treatment of Chagas disease.

“In the study, Lampit showed good antiprotozoal activity in patients from 0 to 17 years old,” said Jaime Altcheh, MD, head of the Department of Parasitology and Chagas disease at the Ricardo Gutierrez Children’s Hospital in Buenos Aires, Argentina, and coordinating investigator of the Phase III trial.

The Phase III Lampit study was the first part of a prospective, randomized (to dosing regimen), double-blind evaluation of the efficacy, safety, and pharmacokinetics of nifurtimox in 330 children with Chagas disease.1 The study was conducted at 25 investigational sites in Argentina, Bolivia, and Colombia between 2016 and 2018.7 In the study, 330 pediatric patients with serologic evidence of T. cruzi infection (without Chagas disease-related cardiovascular and/or gastrointestinal symptoms) were randomly assigned in a 2:1 fashion to receive either a 60-day (n=219) or a 30-day (n=111) Lampit treatment regimen, and were followed up for one year after end of treatment.1 The results showed superiority in favor of the nifurtimox 60-day arm compared to the nifurtimox 30-day arm (not an approved dosing regimen). For additional clinical trial information, go to clinicaltrials.gov NCT02625974 and see full prescribing information. 

The study will continue with a second part (Lampit SECURE) to follow patients for an additional three years to confirm efficacy and safety.

Now that Lampit is approved for pediatric use in the U.S., Bayer is working to ensure access to the drug for all patients through retail channels. Commercially insured patients may qualify for a $0 co-pay to help with their out-of-pocket costs. For uninsured patients who cannot afford Lampit, the Bayer U.S. Patient Assistance Foundation, a charitable organization, will help eligible patients obtain the prescription medication at no cost. Restrictions apply. See Program Details for full information. Lampit is not approved in the U.S. for use in adults 18 years of age or older.

https://www.rxlist.com/lampit-drug.htm

FDA Approves Lampit (nifurtimox) for the Treatment of Chagas Disease in Children

FDA Approves Ruzurgi (amifampridine) for Children with Lambert-Eaton Myasthenic Syndrome

In continuation of my update on amifampridine

The U.S. Food and Drug Administration approved Ruzurgi (amifampridine) tablets for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 years to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. The only other treatment approved for LEMS is only approved for use in adults.

“We continue to be committed to facilitating the development and approval of treatments for rare diseases, particularly those in children,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities.”

LEMS is a rare autoimmune disorder that affects the connection between nerves and muscles and causes weakness and other symptoms in affected patients. In people with LEMS, the body’s own immune system attacks the neuromuscular junction (the connection between nerves and muscles) and disrupts the ability of nerve cells to send signals to muscle cells. LEMS may be associated with other autoimmune diseases, but more commonly occurs in patients with cancer such as small cell lung cancer, where its onset precedes or coincides with the diagnosis of cancer. LEMS can occur at any age. The prevalence of LEMS specifically in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide.

Use of Ruzurgi in patients 6 to less than 17 years of age is supported by evidence from adequate and well-controlled studies of the drug in adults with LEMS, pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients and safety data from pediatric patients 6 to less than 17 years of age.

The effectiveness of Ruzurgi for the treatment of LEMS was established by a randomized, double-blind, placebo-controlled withdrawal study of 32 adult patients in which patients were taking Ruzurgi for at least three months prior to entering the study. The study compared patients continuing on Ruzurgi to patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients that continued on Ruzurgi experienced less impairment than those on placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness that evaluated the feeling of weakening or strengthening. The scores indicated greater perceived weakening in the patients switched to placebo.

The most common side effects experienced by pediatric and adult patients taking Ruzurgi were burning or prickling sensation (paresthesia), abdominal pain, indigestion, dizziness and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Patients should inform their health care professional immediately if they have signs of hypersensitivity reactions such as rash, hives, itching, fever, swelling or trouble breathing.

The FDA granted this application Priority Review and Fast Track designations. Ruzurgi also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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

FDA Approves Ruzurgi (amifampridine) for Children with Lambert-Eaton Myasthenic Syndrome