FDA Approves Auvelity (dextromethorphan and bupropion) for the Treatment of Major Depressive Disorder in Adults

 

        

dextromethorphan

 

Bupropion

In continuation of my updates on dextromethorphan and Bupropion, 

Axsome Therapeutics, Inc. , a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders,  announced  the U.S. Food and Drug Administration (FDA)  approval of  Auvelity (dextromethorphan HBr -bupropion HCl) extended-release tablets for the treatment of major depressive disorder (MDD) in adults.¹ Auvelity is the first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week.  The rapid antidepressant effects of Auvelity were sustained at all subsequent timepoints. Auvelity is the first and only oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of MDD.  Axsome anticipates Auvelity to be commercially available in the U.S. in the fourth quarter of 2022.

Maurizio Fava, MD, Psychiatrist-In-Chief, Department of Psychiatry, Massachusetts General Hospital, Executive Director, Clinical Trials Network & Institute, Associate Dean for Clinical & Translational Research, and Slater Family Professor of Psychiatry, Harvard Medical School said, “The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile. Auvelity, which was granted Breakthrough Therapy designation by the FDA, represents the first new oral non-monoamine-based mechanism of action approved to treat major depressive disorder in over sixty years. Nearly two thirds of patients treated with currently available antidepressants do not adequately respond, and those that do may not achieve clinically meaningful responses for up to six to eight weeks. Given the debilitating nature of depression, the efficacy of Auvelity observed at one week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition.”

Michael Pollock, Chief Executive Officer of the Depression and Bipolar Support Alliance (DBSA), a leading national patient advocacy organization focusing on depression and bipolar disorder said, “The mental health crisis in the United States is one of the most pressing health issues facing our country today. Over 20 million American adults experienced major depressive disorder each year prior to the COVID-19 pandemic. These numbers increased dramatically during the pandemic with approximately thirty percent of adults in the U.S. or more than 80 million Americans experiencing elevated symptoms of depression. The need for new treatment options, particularly those with new mechanisms of action, could not be clearer and more urgent for those living with, or impacted by, major depressive disorder.”

Dan V. Iosifescu, MD, Professor of Psychiatry at the New York University School of Medicine, and Director of the Clinical Research Division at the Nathan Kline Institute for Psychiatric Research said, “Major depressive disorder is disabling and potentially life-threatening, causes profound distress for patients and their families, and leads to substantial healthcare resource utilization. Auvelity’s oral NMDA receptor antagonist and sigma-1 receptor agonist activity, which targets glutamatergic neurotransmission, provides clinicians a long sought after new mechanistic approach which may benefit the millions of patients living with this serious condition. In clinical trials, Auvelity has demonstrated rapid and statistically significant improvement in depressive symptoms as early as Week 1, and increased rates of remission at Week 2 compared with placebo. This early benefit with Auvelity was maintained and increased with continued treatment, and was accompanied by a favorable safety and tolerability profile.”

Auvelity was studied in a comprehensive clinical program which included more than 1,100 patients with depression. The efficacy of Auvelity in the treatment of MDD was demonstrated in the GEMINI placebo-controlled study, and confirmatory evidence which included the ASCEND study comparing Auvelity to bupropion sustained-release tablets. In the GEMENI study, Auvelity was statistically significantly superior to placebo in improvement of depressive symptoms as measured by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6, the study’s primary endpoint. To evaluate speed of onset of action, the change in MADRS total score from baseline to Week 1 and from baseline to Week 2 were pre-specified secondary efficacy endpoints. The difference between Auvelity and placebo in change from baseline in MADRS total score was statistically significant at Week 1 and at Week 2.¹ In the ASCEND study, Auvelity was statistically significantly superior to bupropion sustained-release tablets 105 mg twice daily on the primary outcome measure.⁵ The primary outcome measure of the ASCEND study was calculated by assessing the change from baseline in MADRS total scores from Week 1 to Week 6 and then taking the average of those scores.¹ In the placebo-controlled clinical study, the most common (incidence ≥5% for Auvelity and more than twice as frequently as placebo) adverse reactions were dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.¹

The FDA granted Breakthrough Therapy designation for Auvelity for the treatment of MDD in March 2019. This designation is granted to candidate drugs that show potential for benefit above that of available therapies based on preliminary clinical data, and it provides the sponsor with added focus from and greater interactions with FDA staff during the development of the candidate drug.⁶ The Auvelity New Drug Application (NDA) was evaluated by the FDA under Priority Review, which is granted by the FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

 

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

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

 

FDA Approves Konvomep (omeprazole and sodium bicarbonate for oral suspension) for Gastric Ulcer and Reduction of Risk of Gastrointestinal Bleeding in Critically Ill Patients

 

 

 In continuation of my update on omeprazole

Azurity Pharmaceuticals, Inc., a pharmaceutical company focused on developing innovative dose-forms and formulations of products to serve the needs of overlooked patients, announced the U.S. Food and Drug Administration (FDA)   approval of  Konvomep (omeprazole and sodium bicarbonate for oral suspension). Konvomep is approved for the treatment of active benign gastric ulcer and reduction of risk of upper gastrointestinal bleeding in critically ill patients.

“We are very pleased that patients will soon have access to this FDA-approved oral liquid formulation option of a commonly prescribed proton pump inhibitor¹,” said Richard Blackburn, CEO of Azurity Pharmaceuticals. “Patients are our priority, and our purpose is to bring them new formulations that help them benefit from established medicines. Konvomep™ may give patients, particularly patients with difficulty swallowing pills or capsules, an option for treatment tailored to their needs.”

“Patients who struggle with taking solid oral dosage forms may be overlooked and have historically had limited FDA-approved treatment options available as liquid formulations,” said Olga Hilas, PharmD, MPH, BCPS, BCGP, Professor, Clinical Health Professions, St. John’s University College of Pharmacy & Health Sciences, Queens, New York.

 

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

 

FDA Approves Sotyktu (deucravacitinib) for the Treatment of Adults with Moderate-to-Severe Plaque Psoriasis

 

Bristol Myers Squibb (NYSE: BMY)   announced   the U.S. Food and Drug Administration (FDA) approval of  Sotyktu™(deucravacitinib), a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Sotyktu is not recommended for use in combination with other potent immunosuppressants.

 

 

The approval is based on results from the pivotal Phase 3 POETYK PSO-1 and POETYK PSO-2 clinical trials, which demonstrated superior efficacy of once-daily Sotyktu compared to placebo and twice-daily Otezla^® (apremilast) in 1,684 patients aged 18 years and older with moderate-to-severe plaque psoriasis.¹ The superior efficacy of Sotyktu compared to placebo and Otezla was demonstrated at both 16 and 24 weeks, and responses with Sotyktu persisted through 52 weeks. See below for more information.

“Sotyktu has the potential to become the new standard of care oral treatment for people with moderate-to-severe plaque psoriasis, given its profile in helping patients achieve clearer skin as demonstrated in the POETYK PSO clinical program,” said April Armstrong, MD, MPH, clinical investigator in the POETYK PSO-1 trial and Associate Dean and Professor of Dermatology at the University of Southern California. “People living with moderate-to-severe plaque psoriasis face significant burdens, and Sotyktu is a welcome first-line systemic treatment option.”

Psoriasis is a widely prevalent, chronic, systemic immune-mediated disease that affects approximately 7.5 million people in the U.S.³ Up to 90 percent of patients with psoriasis have plaque psoriasis, which is characterized by distinct, round or oval plaques typically covered by silvery white scales. Nearly one-quarter of people with psoriasis, or around two million in the U.S., have cases that are considered moderate-to-severe.

“The approval of Sotyktu represents an exciting day for patients suffering from moderate-to-severe plaque psoriasis who are not satisfied with topical and conventional treatments. This is another extraordinary achievement for Bristol Myers Squibb, as we bring forward a new mechanism of action, the first oral treatment approved in nearly 10 years, and the first orally dosed once-daily treatment for moderate-to-severe plaque psoriasis,” said Samit Hirawat, MD, Chief Medical Officer, Bristol Myers Squibb. “We believe Sotyktu is a breakthrough in the treatment of patients with this condition, and we’re excited about its potential in other immune-mediated diseases.”

In the POETYK PSO trials, at Week 16, the most common adverse reactions (≥1 percent and higher than placebo) in patients on Sotyktu were upper respiratory infections (19.2 percent), blood creatine phosphokinase increase (2.7 percent), herpes simplex (2.0 percent), mouth ulcers (1.9 percent), folliculitis (1.7 percent) and acne (1.4 percent).¹ In addition, 2.4 percent of patients on Sotyktu, 3.8 percent of patients on placebo, and 5.2 percent of patients on Otezla experienced adverse reactions leading to discontinuation.

“Despite the availability of therapies, many people living with plaque psoriasis in the United States are untreated or undertreated,^5,6” said Leah M. Howard, JD, President and CEO of the National Psoriasis Foundation. “The FDA approval of a new oral treatment is exciting news for the psoriasis community. We welcome this new treatment option.”

 

 

 

 

 

 

FDA Approves Sotyktu (deucravacitinib) for the Treatment of Adults with Moderate-to-Severe Plaque Psoriasis

FDA Approves Terlivaz (terlipressin) for the Treatment of Hepatorenal Syndrome (HRS)

Mallinckrodt plc (OTCMKTS: MNKPF), a global specialty pharmaceutical company,   announced  the U.S. Food and Drug Administration (FDA) approval of  Terlivaz (terlipressin) for injection. Terlivaz is the first and only FDA-approved product indicated to improve kidney function in adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function, an acute and life-threatening condition requiring hospitalization.

 

 

Please see Limitation of Use and Important Safety Information, including Boxed Warning, below.

Siggi Olafsson, President and Chief Executive Officer, said, "The FDA approval of Terlivaz is a significant milestone for Mallinckrodt as it brings an important treatment option to these critically ill patients requiring hospitalization and to U.S. physicians who historically have had limited treatment interventions. We're excited to bring Terlivaz to U.S. patients and physicians and plan to launch the product in the coming weeks. This approval reflects Mallinckrodt's continued commitment to underserved patients and their caregivers through our demonstrated expertise and dedication to developing therapeutics for critical conditions."

Terlipressin is recommended by the American Association for the Study of Liver Diseases (AASLD) guidance and the American College of Gastroenterology (ACG) guidelines.*^, Terlipressin is one of the most studied pharmacological agents in HRS with more than 70 published manuscripts and presented abstracts on clinical data to date. It has been approved outside the U.S. for more than 30 years and is available on five continents for its indications in the countries where it is approved.

The FDA approval was based, in part, on results from the Phase 3 CONFIRM trial, the largest-ever prospective study (n=300) conducted to assess the safety and efficacy of terlipressin in patients with HRS type 1 (HRS-1) in the U.S. and Canada. The CONFIRM trial met its primary endpoint of Verified HRS Reversal, defined as renal function improvement, avoidance of dialysis and short-term survival (p=0.012).  To achieve Verified HRS Reversal, patients had to have two consecutive serum creatinine (SCr) values of ≤1.5 mg/dL, at least two hours apart by day 14 or hospital discharge. To be included in the primary efficacy endpoint analysis, patients had to be alive and without intervening renal replacement therapy (e.g., dialysis) at least 10 days after achieving Verified HRS Reversal. Initial results were presented in a late-breaking session at The Liver Meeting^® 2019, the annual meeting of AASLD. Results were also published in the New England Journal of Medicine in March of 2021. The CONFIRM trial was completed prior to the updated diagnostic criteria and terminology published in the 2021 AASLD guidance on hepatorenal syndrome.

Steven Romano, M.D., Executive Vice President and Chief Scientific Officer at Mallinckrodt said, "Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it. Terlivaz gives U.S. physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function¹ that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis."

The most commonly observed adverse reactions in at least 4 percent of patients treated with Terlivaz compared to placebo were abdominal pain reported in 19.5 percent (n=39) of patients (vs. 6.1%; n=6), nausea reported in 16 percent (n=32) of patients (vs. 10.1%; n=10), respiratory failure reported in 15.5 percent (n=31) of patients (vs. 7.1%; n=7) diarrhea reported in 13 percent (n=26) of patients (vs. 7.1%; n=7) and dyspnea reported in 12.5 percent (n=25) of patients (vs. 5.1%; n=5).¹

 

FDA Approves Aponvie (aprepitant) for the Prevention of Postoperative Nausea and Vomiting (PONV)

In continuation of my update on aprepitant

 

 

 

Heron Therapeutics, Inc., a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs,  announced  the U.S. Food and Drug Administration (FDA)   approval of  Aponvie (aprepitant) injectable emulsion, for intravenous use for the prevention of postoperative nausea and vomiting (PONV) in adults. 

Aponvie is the first and only IV formulation of aprepitant for PONV prevention. Administered via a single 30-second IV injection, Aponvie reaches drug levels associated with ≥97% receptor occupancy in the brain within five minutes and maintains therapeutic plasma concentrations for at least 48 hours. Aponvie is provided in a single-dose vial that delivers the full 32 mg dose approved for PONV. This ready-to-use, easy to administer, innovative IV formulation ensures rapid and consistent exposure in patients undergoing surgery.

An important component of the FDA approval of Aponvie were results from two multicenter, randomized, double-blind clinical studies comparing oral aprepitant to current standard of care, IV ondansetron, for the prevention of PONV in patients during the 48 hours following open abdominal surgery demonstrating that aprepitant was more effective than ondansetron in preventing vomiting. Treatment with aprepitant resulted in approximately 50% fewer patients vomiting in the first 24 and 48 hours compared to ondansetron. In clinical studies, Aponvie was well-tolerated and presented a safety profile comparable to oral aprepitant.

In a 2020 Cochrane meta-analysis, aprepitant was ranked as the most effective drug approved for PONV prophylaxis, being the most effective for the prevention of vomiting in the first 24 hours post-surgery and the drug with the fewest adverse events.

"With the approval of Aponvie our acute care portfolio now addresses the two most common concerns of patients and clinicians after surgery, postoperative pain and postoperative nausea and vomiting. This marks an important milestone for our expanding acute care portfolio and is a testament to our ongoing commitment to developing innovative solutions to help improve the overall patient experience after surgery," said Barry Quart, Pharm.D., Chairman and Chief Executive Officer of Heron. "With approximately 36 million procedures in the U.S. each year in patients with high to moderate risk for PONV, the approval of Aponvie provides an easy to use, highly effective option for these patients that fits seamlessly into our acute care franchise."

PONV are common adverse effects of anesthesia and surgery, with an estimated 30 percent of patients receiving general anesthesia and up to 80 percent of high-risk patients experiencing these symptoms, necessitating more effective preventative agents. PONV is a major cause of patient dissatisfaction after surgery, with patients frequently ranking vomiting as the most undesirable outcome of anesthesia. Additionally, PONV presents a significant risk in outpatient surgeries as patients are often discharged within hours after surgery and no longer have access to highly effective antiemetics.

"PONV is commonly experienced after surgery and may result in increased hospital stays, prolonged recovery time, and decreased patient satisfaction" said Ashraf Habib, MBBCh, MSc, MHSc, FRCA, Chief, Division of Women's Anesthesia at Duke University Hospital. "Oral aprepitant has been used to prevent postoperative nausea and vomiting for more than 16 years and it is exciting to see that, with the approval of Aponvie, physicians can now offer patients a more convenient IV injection that delivers the same effective treatment, with a 48-hour duration of effect, in a rapid, consistent and reliable way, ensuring a better experience for patients postoperatively."
 
 

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.

FDA Approves Amvuttra (vutrisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the U.S. Food and Drug Administration (FDA) approved Amvuttra (vutrisiran), an RNAi therapeutic administered via subcutaneous injection once every three months (quarterly) for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. hATTR amyloidosis is a rare, inherited, rapidly progressive, and fatal disease with debilitating polyneuropathy manifestations, for which there are few treatment options. The FDA approval is based on positive 9-month results from the HELIOS-A Phase 3 study, where Amvuttra significantly improved the signs and symptoms of polyneuropathy, with more than 50 percent of patients experiencing halting or reversal of their disease manifestations.

“Twenty years ago, Alnylam was founded with the bold vision for RNA interference to make a meaningful impact on the lives of people around the world in need of new approaches to address serious diseases with significant unmet medical needs, such as hATTR amyloidosis. Today, Amvuttra has the potential to change the standard of care for people living with the polyneuropathy of this devastating disease,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam Pharmaceuticals. “We are so thankful to the patients, families and investigators involved in making Amvuttra a reality for the hATTR amyloidosis community. As the fifth RNAi therapeutic developed by Alnylam to receive regulatory approval in less than four years, we believe Amvuttra represents an important milestone that brings us one step closer to achieving our P5x25 goals aimed at Alnylam’s transition to a leading biotech company.”

The FDA approval of Amvuttra is based on positive 9-month results from HELIOS-A, a global, randomized, open-label, multicenter, Phase 3 study that evaluated the efficacy and safety of Amvuttra across a diverse group of patients with hATTR amyloidosis with polyneuropathy. 164 patients with hATTR amyloidosis were randomized 3:1 to receive either 25 mg of vutrisiran (N=122) via subcutaneous injection once every three months or 0.3 mg/kg of patisiran (N=42) via intravenous infusion once every three weeks (reference group) for 18 months. The efficacy of Amvuttra was assessed by comparing the Amvuttra group in HELIOS-A with the placebo group (n=77) from the landmark APOLLO Phase 3 study of patisiran, a randomized controlled study in a comparable patient population.

Amvuttra met the primary endpoint of the study, the change from baseline in the modified Neuropathy Impairment Score + 7 (mNIS+7) at 9 months. Treatment with Amvuttra (N=114) resulted in a 2.2 point mean decrease (improvement) in mNIS+7 from baseline as compared to a 14.8 point mean increase (worsening) reported for the external placebo group (N=67), resulting in a 17.0 point mean difference relative to placebo (p<0.0001); by 9 months, 50 percent of patients treated with Amvuttra experienced improvement in neuropathy impairment relative to baseline.

Amvuttra also met all secondary endpoints in the study at 9 months, with significant improvement in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) score and timed 10-meter walk test (10-MWT), and improvements were observed in exploratory endpoints, including change from baseline in modified body mass index (mBMI), all relative to external placebo. Efficacy results at 18 months were consistent with 9-month data, with Amvuttra achieving statistically significant improvements compared to external placebo for all secondary endpoints including mNIS+7, Norfolk QoL-DN, 10-MWT and mBMI, and non-inferiority in serum TTR reduction relative to the within-study patisiran reference group.

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FDA Approves Amvuttra (vutrisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults

FDA Approves Mounjaro (tirzepatide) Injection for the Treatment of Adults with Type 2 Diabetes

The U.S. Food and Drug Administration (FDA) has approved Mounjaro (tirzepatide) injection, Eli Lilly and Company's (NYSE: LLY) new once-weekly GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Mounjaro has not been studied in patients with a history of pancreatitis and is not indicated for use in patients with type 1 diabetes mellitus.

As the first and only FDA-approved GIP and GLP-1 receptor agonist, Mounjaro is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones.1

"Mounjaro delivered superior and consistent A1C reductions against all of the comparators throughout the SURPASS program, which was designed to assess Mounjaro's efficacy and safety in a broad range of adults with type 2 diabetes who could be treated in clinical practice. The approval of Mounjaro is an exciting step forward for people living with type 2 diabetes given the results seen in these clinical trials," said Juan Pablo Frías, M.D., Medical Director, National Research Institute and Investigator in the SURPASS program.

Mounjaro will be available in six doses (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg) and will come in Lilly's well-established auto-injector pen with a pre-attached, hidden needle that patients do not need to handle or see.

The approval was based on results from the phase 3 SURPASS program, which included active comparators of injectable semaglutide 1 mg, insulin glargine and insulin degludec. Efficacy was evaluated for Mounjaro 5 mg, 10 mg and 15 mg used alone or in combination with commonly prescribed diabetes medications, including metformin, SGLT2 inhibitors, sulfonylureas and insulin glargine. Participants in the SURPASS program achieved average A1C reductions between 1.8% and 2.1% for Mounjaro 5 mg and between 1.7% and 2.4% for both Mounjaro 10 mg and Mounjaro 15 mg. While not indicated for weight loss, mean change in body weight was a key secondary endpoint in all SURPASS studies. Participants treated with Mounjaro lost between 12 lb. (5 mg) and 25 lb. (15 mg) on average.1

Side effects reported in at least 5% of patients treated with Mounjaro include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion (dyspepsia), and stomach (abdominal) pain. The labeling for Mounjaro contains a Boxed Warning regarding thyroid C-cell tumors. Mounjaro is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2.1

"Lilly has a nearly 100-year heritage of advancing care for people living with diabetes – never settling for current outcomes. We're not satisfied knowing that half of the more than 30 million Americans living with type 2 diabetes are not reaching their target blood glucose levels," said Mike Mason, president, Lilly Diabetes. "We are thrilled to introduce Mounjaro, which represents the first new class of type 2 diabetes medication introduced in almost a decade and embodies our mission to bring innovative new therapies to the diabetes community."

More at 

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

FDA Approves Radicava ORS (edaravone) for the Treatment of Amyotrophic Lateral Sclerosis (ALS)

Mitsubishi Tanabe Pharma Corporation (MTPA)   announced the U.S. Food and Drug Administration (FDA)   approval of Radicava ORS (edaravone), the oral form of edaravone, for the treatment of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that currently has no cure and can progress rapidly.  Radicava ORS offers the same efficacy as Radicava (edaravone), an FDA-approved intravenous (IV) treatment shown in a pivotal trial to help slow the loss of physical function in ALS. 

"At MTPA, patients have been the driving force behind our work as we strive to develop meaningful treatment options for ALS and continue to tackle unmet needs," said Atsushi Fujimoto, President, MTPA. "Five years ago, we proudly launched Radicava as a treatment option for patients with ALS in the U.S. Now, we continue to push the boundaries of innovation with Radicava ORS, an orally administered option allowing patients flexibility in how they take their medicine."

Radicava ORS is specifically formulated for patients with ALS and provides a flexible administration option (taken orally or via feeding tube) with a small, 5 mL dose, a portable bottle, an oral dosing syringe and no need for patients to refrigerate or reconstitute before taking.1 With appropriate instruction from a healthcare provider (HCP), Radicava ORS may take only a few minutes to administer on treatment days.1 Radicava ORS should be taken in the morning after overnight fasting.1 To learn more about Radicava ORS, visit Radicava.com/update.

"ALS is a progressive disease that, due to its heterogenous nature, impacts patients at different rates with varying symptoms," said Tulio Bertorini, M.D., Professor of Neurology, The University of Tennessee Health Science Center. "Therefore, it is crucial that patients have treatment and formulation options that accommodate their own unique needs, and Radicava ORS provides HCPs who have prescribed their ALS patients edaravone with an alternate delivery option."

The comprehensive clinical development program for edaravone in ALS has spanned over a decade and included multiple clinical trials for the IV and oral formulations. The FDA approval of Radicava ORS is supported by several studies, including data from the pivotal Phase 3 clinical trial (MCI186-19) evaluating 137 ALS patients that showed treatment with Radicava slowed the loss of physical function by 33 percent (approximately one-third) compared to placebo at 24 weeks, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), a validated rating instrument for monitoring disease progression in patients.1Additionally, seven Phase 1 clinical pharmacology studies were conducted to examine the pharmacokinetics, safety, drug-to-drug interactions, dosing, bioavailability and bioequivalence of Radicava ORS in healthy individuals and ALS patients with and without a percutaneous endoscopic gastrostomy (PEG) tube/nasogastric (NG) tube, as well as a global Phase 3, 24-week trial demonstrating the safety and tolerability profile of the treatment in 185 patients with ALS. Lastly, there is an ongoing Phase 3 study evaluating the long-term safety and tolerability of Radicava ORS for up to 96 weeks.

The most common adverse events that occurred in greater than 10 percent of patients treated with Radicava were bruising (contusion), problems walking (gait disturbance) and headache. Fatigue was observed in 7.6 percent of patients taking Radicava ORS.  Radicava and Radicava ORS are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product.1 Hypersensitivity reactions and anaphylactic reactions have been reported in patients treated with Radicava.

More at..

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