FDA Approves Viltepso (viltolarsen) for the Treatment of Duchenne Muscular Dystrophy in Patients Amenable to Exon 53 Skipping Therapy

NS Pharma, Inc. announced  the U.S. Food & Drug Administration (FDA) has approved Viltepso (viltolarsen) injection for patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 53 skipping therapy. Viltepso received an Accelerated Approval by the FDA based on an increase in dystrophin, a key protein for supporting muscle health. Since a lack of dystrophin is the underlying cause of DMD, increasing dystrophin as much and as early as possible is a key goal in the treatment of DMD. Viltepso is the first and only exon 53 skipping therapy to demonstrate an increase in dystrophin in children as young as four years old. The continued approval of Viltepso may be contingent on confirmation of a clinical benefit in a Phase 3 confirmatory trial.

DMD is caused by genetic mutations that prevent dystrophin production. Patients with DMD experience progressive and irreversible muscle loss with symptoms appearing as early as two years of age. Cardiac and respiratory muscle problems begin in the teenage years and lead to serious, life-threatening complications.

The Viltepso New Drug Application (NDA) submission included results from a Phase 2, two-period study in patients aged four to less than 10 years of age conducted in North America (Study 1, N=16) and a multicenter, open-label study in boys five to less than 18 years of age conducted in Japan (Study 2, N=16).

In Study 1, of those patients who received the recommended dose of 80 mg/kg/wk (N=8), 100% of patients (8/8) showed an increase in dystrophin levels after treatment with Viltepso and 88% of patients (7/8) showed dystrophin levels of 3% or greater than normal. Overall, after 20-24 weeks of treatment a mean increase in dystrophin expression to nearly 6% of normal was observed with Viltepso (80 mg/kg/wk) versus 0.6% at baseline.

The most common side effects of Viltepso included upper respiratory tract infection, injection site reaction, cough and fever.

"For decades, neurologists who treat DMD have hoped for the discovery of therapies capable of significantly improving dystrophin production, and the magnitude of dystrophin increases observed with Viltepso are impressive," said study investigator Vamshi Rao, MD, Ann & Robert H. Lurie Children's Hospital of Chicago. "The approval of Viltepso is an exciting development for DMD patients amenable to exon 53 skipping therapy and may rapidly become a foundational treatment for these patients."

Patients receiving treatment with Viltepso have the option and flexibility to receive infusions at their home or at a hospital or treatment center. Viltepso is administered by a trained healthcare professional as an 80 mg per kg of body weight 60-minute weekly intravenous infusion.

NS Pharma will provide families, physicians and healthcare professionals dedicated and individualized resources every step of the way through the NS Support program. NS Pharma will be hosting a series of webinars on the comprehensive care coordination available through NS Support. Follow us on LinkedIn and Twitter for information and registration for upcoming webinars.

"On behalf of NS Pharma and Nippon Shinyaku, I would like to express our deepest gratitude to the families and physicians who participated in our clinical trials and made today's approval possible," said Tsugio Tanaka, President, NS Pharma, Inc. "We are proud to now offer an important new treatment option to help address the significant unmet needs caused by this devastating disease."

NS Pharma continues to study the safety and efficacy of Viltepso in the confirmatory Phase 3 RACER53 trial. This study was initiated in October 2019 and is currently enrolling. The purpose of this Phase 3 trial is to confirm the clinical findings that were submitted under the Accelerated Approval pathway.

https://www.rxlist.com/viltepso-drug.htm#description

FDA Approves Viltepso (viltolarsen) for the Treatment of Duchenne Muscular Dystrophy in Patients Amenable to Exon 53 Skipping Therapy

FDA Approves Evrysdi (risdiplam) for Treatment of Spinal Muscular Atrophy (SMA) in Adults and Children 2 Months and Older

Genentech, a member of the Roche Group, announced the U.S. Food and Drug Administration (FDA) approval of Evrysdi (risdiplam) for treatment of spinal muscular atrophy (SMA) in adults and children 2 months of age and older. Evrysdi showed clinically-meaningful improvements in motor function across two clinical trials in people with varying ages and levels of disease severity, including Types 1, 2, and 3 SMA. Infants achieved the ability to sit without support for at least 5 seconds, a key motor milestone not normally seen in the natural course of the disease. Evrysdi also improved survival without permanent ventilation at 12 and 23 months, compared to natural history. A liquid medicine, Evrysdi is administered daily at home by mouth or feeding tube.

“Given the majority of people with SMA in the U.S. remain untreated, we believe Evrysdi, with its favorable clinical profile and oral administration, may offer meaningful benefits for many living with this rare neurological disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “The strength and resolve of the SMA community has continually inspired us as we developed this first-of-its-kind medicine for SMA, so today we celebrate our collective accomplishment together with them.”

Evrysdi is being studied in more than 450 people as part of a large and robust clinical trial program in SMA. The program includes infants aged 2 months to adults aged 60 with varying symptoms and motor function, such as people with scoliosis or joint contractures, and those previously treated for SMA with another medication. The approval is based on data from two clinical studies designed to represent a broad spectrum of people living with SMA: FIREFISH in symptomatic infants aged 2 to 7 months; and SUNFISH in children and adults aged 2 to 25 years. SUNFISH is the first and only placebo-controlled trial to include adults with Types 2 and 3 SMA.

In FIREFISH, 41% (7/17) of infants treated with the therapeutic dose achieved the ability to sit without support for at least 5 seconds as measured by the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). Additionally, 90% (19/21) of infants were alive without permanent ventilation at 12 months of treatment and reached 15 months of age or older. As described in the natural history of untreated infantile-onset SMA, infants would not be expected to be able to sit independently, and only 25% would be expected to survive without permanent ventilation beyond 14 months of age. In SUNFISH, children and adults treated with Evrysdi experienced a clinically-meaningful and statistical-significant improvement in motor function at 12 months (1.55 point mean difference; p=0.0156) compared to placebo (1.36 points [95% CI: 0.61, 2.11]; -0.19 points [95% CI: -1.22, 0.84], respectively), as measured by a change from baseline in the Motor Function Measure-32 (MFM-32) total score.

Evrysdi demonstrated a favorable efficacy and safety profile, with the safety profile established across the FIREFISH and SUNFISH trials. The most common adverse reactions were fever, diarrhea, and rash in later-onset SMA. In infantile-onset SMA, the most common adverse events were similar and also included upper respiratory tract infection, pneumonia, constipation, and vomiting. There were no treatment-related safety findings leading to withdrawal from either study.

“Throughout their lives, many people with SMA may lose their ability to perform critical movements, which can impact the ability to independently participate in aspects of daily life and even be life altering,” said Kenneth Hobby, president of Cure SMA. “The approval of Evrysdi is an eagerly awaited milestone for our community. We appreciate Genentech’s commitment to reflecting the full scope of the real-world SMA population in their clinical trial program and developing a treatment that can be administered at home.”

Evrysdi is designed to treat SMA by increasing production of the survival of motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement. Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Evrysdi will be available in the United States within two weeks for direct delivery to patients’ homes through Accredo Health Group Inc., an Express Scripts specialty pharmacy.

Genentech is committed to helping patients access the medicines prescribed by their physician. For people with SMA, the MySMA Support program team is available to answer questions, provide product education and help families understand insurance coverage and navigate appropriate financial assistance options to start and stay on Evrysdi. Patients can call 1-833-EVRYSDI or visit http://www.Evrysdi.com or https://www.Genentech-Access.com to learn more.

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

FDA Approves Evrysdi (risdiplam) for Treatment of Spinal Muscular Atrophy (SMA) in Adults and Children 2 Months and Older

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

Fluvoxamine may prevent serious illness in COVID-19 patients, study suggests: Antidepressant drug repurposed for patients with coronavirus infection

In a preliminary study of COVID-19 patients with mild-to-moderate disease who were attempting to recover in their homes, researchers at Washington University School of Medicine in St. Louis have found that the drug fluvoxamine seems to prevent some of the most serious complications of the illness and make hospitalization and the need for supplemental oxygen less likely.

The study, a collaboration between the university's Department of Psychiatry and Division of Infectious Diseases, involved 152 patients infected with SARS-CoV-2, the virus that causes COVID-19. Researchers compared the outcomes of those treated with fluvoxamine to the outcomes of those given an inactive placebo. After 15 days, none of the 80 patients who had received the drug experienced serious clinical deterioration. Meanwhile, six of the 72 patients given placebo (8.3%) became seriously ill, with four requiring hospitalization.

The study is published online Nov. 12 in the Journal of the American Medical Association.

"The patients who took fluvoxamine did not develop serious breathing difficulties or require hospitalization for problems with lung function," said the paper's first author, Eric J. Lenze, MD, the Wallace and Lucille Renard Professor of Psychiatry. "Most investigational treatments for COVID-19 have been aimed at the very sickest patients, but it's also important to find therapies that prevent patients from getting sick enough to require supplemental oxygen or to have to go to the hospital. Our study suggests fluvoxamine may help fill that niche."

Fluvoxamine is used commonly to treat obsessive-compulsive disorder (OCD), social anxiety disorder and depression. It is in a class of drugs known as selective serotonin-reuptake inhibitors (SSRIs), but unlike other SSRIs, fluvoxamine interacts strongly with a protein called the sigma-1 receptor. That receptor also helps regulate the body's inflammatory response.

"There are several ways this drug might work to help COVID-19 patients, but we think it most likely may be interacting with the sigma-1 receptor to reduce the production of inflammatory molecules," said senior author Angela M Reiersen, MD, an associate professor of psychiatry. "Past research has demonstrated that fluvoxamine can reduce inflammation in animal models of sepsis, and it may be doing something similar in our patients."

Reiersen said the drug's effects on inflammation could prevent the immune system from mounting an overwhelming response, which is thought to occur in some COVID-19 patients who seem to improve after a few days of illness and then worsen. Many of those patients end up hospitalized, and some die.

In an innovative twist to research during the pandemic, the study was conducted remotely. When a symptomatic patient tested positive and enrolled in the study, research staff delivered the medication or inactive placebo to them, along with thermometers, automatic blood pressure monitors and fingertip oxygen sensors.

"Our goal is to help patients who are initially well enough to be at home and to prevent them from getting sick enough to be hospitalized," said Caline Mattar, MD, an assistant professor of medicine in the Division of Infectious Diseases. "What we've seen so far suggests that fluvoxamine may be an important tool in achieving that goal."

For two weeks, subjects took either the antidepressant drug or placebo sugar pills while having daily interactions with members of the research team -- via phone or computer. That allowed patients to report on their symptoms, oxygen levels and other vital signs. If patients suffered shortness of breath or were hospitalized for pneumonia, or their oxygen saturation levels fell below 92%, their conditions were considered to have deteriorated.

"The good news is that not a single person taking the active medication experienced deterioration," Reiersen said. "We believe this drug may be the reason, but we need to study more patients to make sure."

The researchers will begin a larger study in the next few weeks. Lenze, the director of the Healthy Mind Lab at the School of Medicine, is an expert in using mobile and internet technology to conduct clinical trials. He said that although this initial study involved patients in the St. Louis region, the next phase of the research will involve patients from throughout the country.

"We bring the study to the patients, giving them tools to monitor their health at home," Lenze said. "Our hope is that we can keep these patients healthy enough to avoid hospitalization."

This work was supported by the Taylor Family Institute for Innovative Psychiatric Research, the Bantly Foundation, the Center for Brain Research in Mood Disorders at Washington University and the COVID-19 Early Treatment Fund. Additional support from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH). Grant number UL1 TR002345.

Fluvoxamine may prevent serious illness in COVID-19 patients, study suggests: Antidepressant drug repurposed for patients with coronavirus infection