FDA Approves Palsonify (paltusotine) for the Treatment of Acromegaly in Adults

Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced that the U.S. Food and Drug Administration (FDA) approved Palsonify (paltusotine) for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Palsonify, a selectively-targeted somatostatin receptor type 2 nonpeptide (SST2) agonist, is now the first once-daily, oral treatment approved for adults with acromegaly.

“With the FDA approval of our lead therapy Palsonify, today marks a new era for those living with acromegaly and also for Crinetics as a company,” said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. “We are very pleased to be fulfilling our commitment to transforming patient lives. This approval is the first to come from our deep pipeline of first-in-class, small molecule drugs. This would not be possible without the help and partnership of people living with acromegaly, their caretakers, our employees, and the clinical researchers and health care professionals who contributed to Palsonify’s successful development program. Thank you to all involved.”

The approval is based on data from the PATHFNDR-1 and PATHFNDR-2 Phase 3 pivotal trials, which evaluated Palsonify’s safety and efficacy in previously treated and medically untreated adults with acromegaly. Across both trials, Palsonify consistently demonstrated rapid onset, reliable biochemical control, and sustained efficacy.

Participants also reported significant reductions in signs and symptoms associated with acromegaly as measured by the Acromegaly Symptom Diary (ASD) — an FDA-aligned patient-reported outcome tool developed to capture the symptoms that matter to people living with acromegaly. Symptoms include headaches, joint pain, sweating, fatigue, weakness, swelling, and/or numbness/tingling. Palsonify was generally well-tolerated, with no serious adverse events reported in the randomized controlled portion of the trial.

Long-term results from the open-label extension (OLE) phases of both trials were presented at this year’s Endocrine Society’s annual meeting, ENDO 2025, providing further evidence of Palsonify’s ability to deliver durable IGF-1 control, sustained improvements in patient symptom burden, and a consistent safety profile. Ninety-one percent of patients from PATHFNDR-1 and 97 percent of completers from PATHFNDR-2 enrolled in the OLE.

“The PATHFNDR clinical development program set a new standard for acromegaly treatment by demonstrating the ability of Palsonify to drive both biochemical and symptom control, regardless of the degree of underlying disease severity,” said Dr. Shlomo Melmed, Executive Vice President of Medicine and Health Sciences and Dean of the Medical Faculty at Cedars-Sinai, “The approval of Palsonify is a significant advancement for our patients, as there is an unmet need for an easy-to-administer and safe therapeutic option with a rapid action and durable response that can consistently manage acromegaly.”

“For people living with acromegaly, treatment once meant burdensome injections, breakthrough symptoms, and lifestyle sacrifices just to stay on track,” said Jill Sisco, President of Acromegaly Community. “What matters most to our community – maintaining consistent control so the disease doesn’t control us – led us to partner with the FDA on Externally Led Patient-Focused Drug Development meetings. This new treatment reflects that our voices have been heard in shaping the next generation of acromegaly care.”

Palsonify is expected to be available in the U.S. in early October. Crinetics is ensuring broad access to Palsonify by working closely with payers, healthcare providers, and patient advocacy organizations to support those who may benefit from this treatment.

As part of this commitment, Crinetics has launched CrinetiCARE®, a comprehensive support program designed to assist people living with acromegaly throughout their treatment journey. CrinetiCARE provides disease and product education, benefit verification, financial assistance resources, and access to dedicated nurse educators who can offer support with treatment onboarding and ongoing adherence.

A Marketing Authorization Application (MAA) for paltusotine in acromegaly is currently under review for use in the European Union, and the current timeline for the Committee for Medicinal Products and Human Use (CHMP) opinion is the first half of 2026. Crinetics is in partnership with Sanwa Kagaku Kenkyuso (SKK) to develop and commercialize paltusotine for acromegaly in Japan.

Paltusotine is also being evaluated for the treatment of carcinoid syndrome in the pivotal Phase 3 CAREFNDR trial. Global enrollment for CAREFNDR is expected throughout 2025.

Palsonify (paltusotine) INDICATION:

Palsonify is a somatostatin receptor agonist indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS:

Cholelithiasis and Its Complications: Cholelithiasis, including related complications such as acute cholecystitis and pancreatitis, have been reported. Monitor patients periodically. Discontinue Palsonify if complications of cholelithiasis occur and treat appropriately.

Hyperglycemia and Hypoglycemia: Hyperglycemia, diabetes mellitus, or hypoglycemia, may occur. Monitor blood glucose levels when Palsonify treatment is initiated or when dosage is altered. Adjust antidiabetic treatment accordingly.

Cardiovascular Abnormalities: Cardiac conduction abnormalities and other ECG changes such as PR interval prolongation, bradycardia, sinus arrest, and atrioventricular block may occur in patients with acromegaly and were reported in Palsonify clinical trials. Dosage adjustments of concomitant drugs that have bradycardic effects may be necessary.

Thyroid Function Abnormalities: Somatostatin analogs may suppress the secretion of thyroid-stimulating hormone, which may result in hypothyroidism. Periodic assessment of thyroid function is recommended.

Steatorrhea and Malabsorption of Dietary Fats: Somatostatin analog treatment may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new or worsening symptoms are reported with Palsonify, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly.

Vitamin B12 Deficiency: Vitamin B12 deficiency may occur. Monitor vitamin B12 levels, if clinically indicated.

ADVERSE REACTIONS:

Most common adverse reactions (>5%) are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis.

FDA Approves Palsonify (paltusotine) for the Treatment of Acromegaly in Adults

FDA Approves Palsonify (paltusotine) for the Treatment of Acromegaly in Adults

Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced that the U.S. Food and Drug Administration (FDA) approved Palsonify (paltusotine) for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Palsonify, a selectively-targeted somatostatin receptor type 2 nonpeptide (SST2) agonist, is now the first once-daily, oral treatment approved for adults with acromegaly.

“With the FDA approval of our lead therapy Palsonify, today marks a new era for those living with acromegaly and also for Crinetics as a company,” said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. “We are very pleased to be fulfilling our commitment to transforming patient lives. This approval is the first to come from our deep pipeline of first-in-class, small molecule drugs. This would not be possible without the help and partnership of people living with acromegaly, their caretakers, our employees, and the clinical researchers and health care professionals who contributed to Palsonify’s successful development program. Thank you to all involved.”

The approval is based on data from the PATHFNDR-1 and PATHFNDR-2 Phase 3 pivotal trials, which evaluated Palsonify’s safety and efficacy in previously treated and medically untreated adults with acromegaly. Across both trials, Palsonify consistently demonstrated rapid onset, reliable biochemical control, and sustained efficacy.

Participants also reported significant reductions in signs and symptoms associated with acromegaly as measured by the Acromegaly Symptom Diary (ASD) — an FDA-aligned patient-reported outcome tool developed to capture the symptoms that matter to people living with acromegaly. Symptoms include headaches, joint pain, sweating, fatigue, weakness, swelling, and/or numbness/tingling. Palsonify was generally well-tolerated, with no serious adverse events reported in the randomized controlled portion of the trial.

Long-term results from the open-label extension (OLE) phases of both trials were presented at this year’s Endocrine Society’s annual meeting, ENDO 2025, providing further evidence of Palsonify’s ability to deliver durable IGF-1 control, sustained improvements in patient symptom burden, and a consistent safety profile. Ninety-one percent of patients from PATHFNDR-1 and 97 percent of completers from PATHFNDR-2 enrolled in the OLE.

“The PATHFNDR clinical development program set a new standard for acromegaly treatment by demonstrating the ability of Palsonify to drive both biochemical and symptom control, regardless of the degree of underlying disease severity,” said Dr. Shlomo Melmed, Executive Vice President of Medicine and Health Sciences and Dean of the Medical Faculty at Cedars-Sinai, “The approval of Palsonify is a significant advancement for our patients, as there is an unmet need for an easy-to-administer and safe therapeutic option with a rapid action and durable response that can consistently manage acromegaly.”

“For people living with acromegaly, treatment once meant burdensome injections, breakthrough symptoms, and lifestyle sacrifices just to stay on track,” said Jill Sisco, President of Acromegaly Community. “What matters most to our community – maintaining consistent control so the disease doesn’t control us – led us to partner with the FDA on Externally Led Patient-Focused Drug Development meetings. This new treatment reflects that our voices have been heard in shaping the next generation of acromegaly care.”

Palsonify is expected to be available in the U.S. in early October. Crinetics is ensuring broad access to Palsonify by working closely with payers, healthcare providers, and patient advocacy organizations to support those who may benefit from this treatment.

As part of this commitment, Crinetics has launched CrinetiCARE®, a comprehensive support program designed to assist people living with acromegaly throughout their treatment journey. CrinetiCARE provides disease and product education, benefit verification, financial assistance resources, and access to dedicated nurse educators who can offer support with treatment onboarding and ongoing adherence.

https://en.wikipedia.org/wiki/Paltusotine#:~:text=Madan%2C%20Ajay;%20Markison%2C%20Stacy,PMID%2036655128.

FDA Approves Palsonify (paltusotine) for the Treatment of Acromegaly in Adults

FDA Approves Bondlido (lidocaine topical system) for the Treatment of Post-Herpetic Neuralgia

MEDRx announced  the U.S. Food and Drug Administration (FDA)  approval of  Bondlido, a lidocaine patch MEDRx Group and D. Western Therapeutics Institute, Inc. has jointly developed, in adults for relief of pain associated with post-herpetic neuralgia (PHN). Going forward, preparations for the launch will be made, including the selection of sales partners, with sales planned to begin in the US in the first half of 2026.

Bondlido is a new type of lidocaine patch for the treatment of post-herpetic neuralgia that uses the ILTS (Ionic Liquid Transdermal System), an exclusive MEDRx technology incorporating the company’s ionic liquid*2 expertise. By developing this new patch, which targets the market for the Lidoderm® lidocaine patch, MEDRx plans to further enlarge this market. Results of clinical trials indicate that Bondlido has excellent prospects in the lidocaine patch market due to reduced skin irritation, firm adhesion to the skin and the strength to remain on the skin even during physical activity, compared with a targeted model Lidoderm®. In the United States, sales of lidocaine patches were USD 162 million in 2024*3 .

This Approval will have no effect on the forecast for the current fiscal year but are expected to make a medium to long-term contribution to results of operations. Note: This document has been translated from the Japanese original for reference purposes only. In the event of any discrepancy between this translated document and the Japanese original, the original shall prevail.

*1 Lidocaine Lidocaine is a type of local anesthetic that reduces pain by blocking the transmission of pain signals at the ends of nerves.

*2 Ionic liquid An ionic liquid is a salt with a melting point of not more than 100ºC and is also called a room temperature molten salt. Properties include a low melting point, high ion conductivity, high polarity, non-volatility and noncombustibility. Many applications are being examined for ionic liquids, including in solar cells and environmentally responsible reaction solvents. MEDRx was first in the world to discover that converting drugs into ionic liquids and dissolving drugs in ionic liquids can dramatically increase the transdermal permeability of these drugs. MEDRx has gained considerable knowledge involving ionic liquids. There is a library of ionic liquids that are believed to be safe by combining them with compounds that have already been used for human consumption. MEDRx has expertise in selecting ionic liquids that are best suited to increasing the transdermal permeability of targeted drugs. Furthermore, MEDRx has the know-how to produce drugs in a format that is easy to use (patches, ointments, etc.) while retaining the properties of ionic liquids that contain drugs. The exclusive technology for producing transdermal drugs incorporating this knowledge is called the Ionic Liquid Transdermal System (ILTS).

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

FDA Approves Bondlido (lidocaine topical system) for the Treatment of Post-Herpetic Neuralgia

FDA Approves Zusduri (mitomycin) for Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer

UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers,  announced the U.S. Food and Drug Administration (FDA) approval of  Zusduri, the first and only FDA-approved medication for adults with recurrent LG-IR-NMIBC. Zusduri consists of mitomycin and sterile hydrogel, using UroGen’s proprietary sustained release RTGel® technology. Zusduri has been designed for potent tumor ablation. This landmark approval is based on the positive results from the Phase 3 ENVISION trial that demonstrated Zusduri delivers 78% complete response (CR) for patients at 3 months, and of those patients 79% remained event-free 12 months later. 

“The approval of Zusduri represents a significant step forward for our company and for the treatment of recurrent LG-IR-NMIBC," said Liz Barrett, President and CEO of UroGen. "For the first time, the estimated 59,000 U.S. patients facing recurrent LG-IR-NMIBC each year have access to an FDA-approved medicine. This historic achievement is a bold leap forward in our mission to redefine uro-oncology and bring innovation to patients who need it most. We are deeply grateful to the FDA for their collaboration and to the investigators, patients, and caregivers whose commitment made this milestone possible. Their contributions have been essential in bringing meaningful innovation to the bladder cancer community.”

The existing standard of care for LG-IR-NMIBC is a surgical procedure typically performed under general anesthesia called transurethral resection of bladder tumor (TURBT). Due to high recurrence rates of LG-IR-NMIBC, repeat TURBTs may be necessary.

"Zusduri marks a breakthrough in uro-oncology, offering a new alternative for recurrent LG-IR-NMIBC patients who can live for many years with the disease but often endure multiple resections, under general anesthesia,” said Dr. Sandip Prasad, MD, M.Phil., Director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System, NJ, and principal investigator of the ENVISION trial. “For decades, TURBT has been the standard approach for bladder cancer treatment. That’s why innovative treatments like Zusduri are essential, especially for those adult patients with recurrent low-grade, intermediate-risk NMIBC.”

The most common (≥ 10%) adverse reactions, including laboratory abnormalities, that occurred in patients were increased creatinine, increased potassium, dysuria, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, increased eosinophils, decreased lymphocytes, urinary tract infection, decreased neutrophils, and hematuria. Serious adverse reactions occurred in 12% of patients who received Zusduri, including, urinary retention (0.8%) and urethral stenosis (0.4%)

Approves Zusduri (mitomycin) for Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer

FDA Approves Arynta (lisdexamfetamine) Oral Solution for ADHD and Binge Eating Disorder

In continuation of my update on lisdexamfetamine

Food and Drug Administration (FDA) has approved Azurity Pharmaceuticals' Arynta™ (lisdexamfetamine) oral solution for the treatment of attention deficit hyperactivity disorder (ADHD) in adults and pediatric patients 6 years and older, and moderate to severe binge eating disorder (BED) in adults.

Arynta is the first oral solution formulation of lisdexamfetamine, providing a new treatment option for patients who have difficulty swallowing or have a preference for using a liquid dosage form.

Lisdexamfetamine is also available as oral capsules and chewable tablets under the brand name Vyvanse® and generic formulations.

Key Clinical Information

Efficacy: The effectiveness of Arynta has been established based on adequate and well-controlled studies of oral lisdexamfetamine dimesylate in treating adults and pediatric patients 6 years and older with ADHD, and adults with moderate to severe BED.

Dosing for ADHD: The recommended starting dosage is 30 mg once daily in the morning for both adults and pediatric patients 6 years and older. Dosage may be adjusted in increments of 10 mg or 20 mg at weekly intervals, up to a maximum dosage of 70 mg once daily.

Dosing for BED: The recommended starting dosage for adults is 30 mg once daily in the morning, titrated in increments of 20 mg at weekly intervals, up to a maximum dosage of 70 mg once daily. Treatment should be discontinued if binge eating does not improve.

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

FDA Approves Arynta (lisdexamfetamine) Oral Solution for ADHD and Binge Eating Disorder

FDA Approves Harliku (nitisinone) for the Treatment of Patients with Alkaptonuria

In continuation of my update on nitisinone

Cycle Pharmaceuticals has announced   the FDA approval of  Harliku (nitisinone) Tablets for the reduction of urine homogentisic acid (HGA) in adult patients with AKU.1

Launching in July 2025, Harliku will be the first and only FDA-approved treatment for AKU,1 an ultra-rare genetic metabolic disorder in which patients have a buildup of HGA that leads to osteoarthritis, ochronosis, and complications in the kidneys, and heart.2 Patients with AKU often develop pain, reduced joint mobility, and require large joint replacements; the symptoms impede their physical functionality, emotional well-being, and quality of life.2,3

The approval of Harliku is based on data from a randomized, no-treatment controlled study of 40 patients with AKU. As part of the intramural research program of the National Human Genome Research Institute at the National Institutes of Health (NIH), Dr. Wendy J. Introne, MD and her team showed that nitisinone helped patients improve pain, energy levels, and physical functioning after three years of treatment, assessed using the 36-Item Short-Form Survey.4

Steve Fuller, Chief Strategy Officer of Cycle Pharmaceuticals commented,

“We are deeply grateful for Cycle’s collaboration with Dr. Wendy Introne, Dr. Bill Gahl, and the broader team at the NIH, whose pioneering work laid the foundation for this FDA approval. We look forward to making Harliku available to U.S. AKU patients as soon as possible and remain committed to supporting the AKU community to the fullest extent of our capabilities.”

“The approval of Harliku is an important advance for the AKU community. Our scientific team has translated decades of research into launching nitisinone as a new treatment option, and we stand hopeful that it can ease the significant burden of AKU,” said Dr. Wendy J. Introne, MD, of NIH’s National Human Genome Research Institute (NHGRI).

Building on the company’s previous success in rare diseases, Harliku will be Cycle Pharmaceuticals’ eighth commercial product in the US.

Indications

Harliku™ is indicated for the reduction of urine homogentisic acid (HGA) in adult patients with alkaptonuria (AKU).

Important Safety Information

Do not prescribe Harliku to patients allergic to nitisinone or any other contained ingredients.

Warnings and Precautions:

Ocular Symptoms and Hyperkeratotic Plaques Due to Elevated Plasma Tyrosine Level:

Ocular signs and symptoms including keratitis, corneal opacities, corneal irritation, corneal ulcers, conjunctivitis, eye pain, and photophobia, have been reported in patients.

Perform slit-lamp examination prior to treatment and regularly thereafter. Reexamine patients if symptoms develop or tyrosine levels are > 500 micromole/L. Assess plasma tyrosine levels in patients with an abrupt change in neurological status.

Perform a clinical laboratory assessment, including plasma tyrosine levels, in patients with an abrupt change in neurological status.

Leukopenia and Severe Thrombocytopenia

In clinical trials, patients with hereditary tyrosinemia type 1 (HT-1) treated with another oral formulation of nitisinone and dietary restriction, developed reversible leukopenia, thrombocytopenia, or both. No patients developed infections or bleeding as a result of the episodes of leukopenia and thrombocytopenia. Monitor platelet and white blood cell counts during Harliku therapy.

Adverse Reactions:

The most common adverse reactions (≥1%) reported in patients with AKU taking nitisinone in clinical trials are elevated tyrosine levels, thrombocytopenia and keratitis.

Drug Interactions:

Nitisinone is a moderate CYP2C9 inhibitor and a weak CYP2E1 inducer. Potential clinical impact of Harliku administration with CYP2C9 substrates. Reduce the dosage of the co-administered drugs metabolized by CYP2C9 by half. Additional dosage adjustments may be needed.

Nitisinone is an inhibitor of OAT1/OAT3. Potential clinical impact of administration with OAT1/OAT3 substrates. Patients should be monitored for p

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

FDA Approves Harliku (nitisinone) for the Treatment of Patients with Alkaptonuria

FDA Grants Accelerated Approval to Zegfrovy (sunvozertinib) for Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, announced  the U.S. Food and Drug Administration (FDA) approval of  Zegfrovy (sunvozertinib) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins), as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

Zegfrovy, which has received Priority Review and Breakthrough Therapy Designation from the FDA, is the only approved targeted oral treatment for NSCLC with EGFR exon20ins. This indication is approved under Accelerated Approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“We are proud to have developed Zegfrovy, a first-in-class oral therapy that offers a more effective treatment option with enhanced safety and ease of administration for NSCLC patients with EGFR exon20ins,” said Dr. Xiaolin Zhang, CEO of Dizal. “The accelerated approval of Zegfrovy marks a significant milestone that underscores our commitment to developing groundbreaking new medicines for patients with high unmet medical needs around the world.”

Zegfrovy is an oral, irreversible EGFR inhibitor with uniquely designed molecular structure targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. In August 2023, Zegfrovy received accelerated approval in China. Today’s FDA approval follows Breakthrough Therapy Designation and Priority Review granted by both the U.S. FDA and the Center for Drug Evaluation (CDE)of China’s National Medical Products Administration (NMPA).

The FDA approval is supported by data from the multinational pivotal study WU-KONG1 Part B (WU-KONG1B), aiming to investigate the efficacy and safety of Zegfrovy in relapsed or refractory NSCLC with EGFR exon20ins. The study results were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and were recently published in the Journal of Clinical Oncology.

“As the world's only approved targeted oral therapy for EGFR exon20ins NSCLC, Zegfrovy has expanded the treatment paradigm in this therapeutic area that has long lacked convenient and effective treatment options,” said Pasi A. Jänne, MD, PhD, Dana-Farber Cancer Institute of Harvard Medical School and lead principal investigator of WU-KONG1B. “Research findings from WU-KONG1B have demonstrated Zegfrovy’s significant therapeutic effects with consistent efficacy across both Asian and non-Asian patient populations. Its convenient once-daily oral dosing substantially improves administration convenience and patient adherence, which is an increasingly critical factor as lung cancer care shifts toward chronic disease management. The U.S. approval of Zegfrovy® marks a landmark in scientific advancement and represents a meaningful milestone in addressing the long-standing unmet medical needs of this underserved patient population."

“Zegfrovy has demonstrated breakthrough therapeutic value in the treatment of EGFR exon20ins NSCLC, as shown in a rigorous multinational clinical trial. Its potent antitumor activity, manageable safety profile, and convenient oral administration position it as an optimal treatment option in clinical practice,” said Prof. James Chih-Hsin Yang, MD, PhD, National Taiwan University Cancer Center Hospital and the Co-lead principal investigator of WU-KONG1B. “The approval of Zegfrovy in major global markets not only offers new hope for patients, but also reinforces our commitment to patient-centered research and the continued advancement of precision medicine in lung cancer."

“In NSCLC, EGFR exon20ins represent the third most common type of EGFR mutation. EGFR exon20ins are particularly challenging to treat due to their unique spatial conformation, diverse mutation subtypes, and high heterogeneity. As a result, patients face a poor prognosis and limited treatment options,” said Prof. Mengzhao Wang, MD, PhD, lead principal investigator of the China-based pivotal study WU-KONG6 of Zegfrovy and principal investigator of WU-KONG1B at Peking Union Medical College Hospital, “The results of the WU-KONG6 study demonstrated Zegfrovy’s clinical benefit superior to current options and lead to the drug’s approval in China. The U.S. approval of Zegfrovy will enable more patients around the world to benefit from this drug.”

The FDA simultaneously approved Thermo Fisher Scientific’s Oncomine™ Dx Express Test as a next-generation sequencing (NGS) companion diagnostic (CDx) for Zegfrovy to identify NSCLC patients with EGFR Exon20 insertions. NGS testing is recognized as a critical technology in cancer genomic profiling, facilitating the rapid and precise detection of DNA mutations in tumor cells. Combined with the Ion Torrent™ Genexus™ Dx System, the test delivers NGS results in as little as 24 hours to help inform more timely treatment decisions in patients with EGFR exon20ins NSCLC.

Additionally, Dizal has completed enrollment for its multinational phase III pivotal WU-KONG28 study, evaluating Zegfrovy versus platinum-based doublet chemotherapies in treatment naïve NSCLC patients with EGFR exon20ins across 16 countries and regions. At the 2023 European Society for Medical Oncology (ESMO) Annual Meeting, Dizal reported that Zegfrovy, as a single oral agent, achieved a confirmed objective response rate (ORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months in the first-line setting. With its potent antitumor activity and favorable safety profile, Zegfrovy demonstrated strong potential as an optimalfirst-line treatment for patients with EGFR exon20ins NSCLC.

Ref : https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=11672

FDA Grants Accelerated Approval to Zegfrovy (sunvozertinib) for Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

FDA Approves Ekterly (sebetralstat) the First and Only Oral On-demand Treatment for Hereditary Angioedema (HAE)

KalVista Pharmaceuticals, Inc.  announced  the U.S. Food and Drug Administration (FDA) approval of Ekterly (sebetralstat), a novel plasma kallikrein inhibitor, for the treatment of acute attacks of hereditary angioedema (HAE) in adult and pediatric patients aged 12 years and older. Ekterly is the first and only oral on-demand treatment for HAE.

“The FDA approval of Ekterly is a defining moment for people living with HAE,” said Ben Palleiko, CEO of KalVista. “Ekterly enables people to treat attacks the moment symptoms begin, wherever they are. This approval affirms the strength of our science and deep commitment to the HAE community. I am profoundly grateful to the KalVista team for their dedication and perseverance, and to the patients and healthcare providers, as well as the HAEA and HAEi, for making this possible. Ekterly has the potential to become the foundational treatment for HAE, and our focus now is on delivering it to the people who need it.”

“As the first orally administered on-demand therapy for HAE attacks, Ekterly provides patients and physicians with an important and welcome advance in HAE treatment options,” said Anthony J. Castaldo, chief executive officer of the U.S. Hereditary Angioedema Association.

Prior to Ekterly’s approval, all on-demand HAE treatment options approved in the U.S. required intravenous or subcutaneous administration, which carries a significant treatment burden.1 Even with the use of long-term prophylaxis as a preventative therapy, most people living with HAE continue to have unpredictable attacks and require ready access to on-demand medication.1

“This is an important moment for patients, giving people living with HAE a treatment option that could provide greater independence and control over managing their condition,” said Marc A. Riedl, MD, Professor of Medicine and Clinical Director, U.S. Hereditary Angioedema Association Center at the University of California, San Diego, and an investigator for the KONFIDENT phase 3 trial. "Until now, on-demand treatment relied on injectable subcutaneous or intravenous administration, often resulting in delayed intervention. Having an oral option empowers patients to treat attacks early, which aligns with treatment guidelines and advances our goal as physicians to reduce the overall burden of disease.”

The efficacy and safety of Ekterly was established by the results from KalVista’s phase 3 KONFIDENT clinical trial, which was the largest clinical trial program ever conducted in HAE. Data from KONFIDENT was published in the New England Journal of Medicine in May 2024, showing that Ekterly achieved significantly faster symptom relief, reduction in attack severity, and attack resolution than placebo, and was well-tolerated with a safety profile similar to placebo.2 The trial randomized 136 HAE patients from 66 clinical sites across 20 countries. These results were further supported by the more real-world KONFIDENT-S open-label extension trial, which as of September 2024, showed that EKTERLY enabled patients to treat attacks in a median of 10 minutes following onset. The most recent data from KONFIDENT-S shows that beginning of symptom relief occurred in a median of 1.3 hours among attacks involving the larynx, the abdomen, and for breakthrough attacks among patients receiving long-term prophylaxis. The safety profile of EKTERLY 600 mg in KONFIDENT-S, in a much larger number of attacks (>1700), was consistent with that observed in KONFIDENT.

KalVista will launch Ekterly in the U.S. immediately, and physicians can begin writing prescriptions today. As part of the Company’s commitment to supporting patients, KalVista has established KalVista Cares™, a comprehensive patient support program that offers personalized services and resources for eligible individuals. This includes assistance with navigating insurance coverage, access support, and ongoing help throughout the treatment journey.

REF: https://en.wikipedia.org/wiki/Sebetralstat

FDA Approves Ekterly (sebetralstat) the First and Only Oral On-demand Treatment for Hereditary Angioedema (HAE)

FDA Approves Anzupgo (delgocitinib) Cream for the Treatment of Chronic Hand Eczema

LEO Pharma, a global leader in medical dermatology, announced   the U.S. Food and Drug Administration (FDA) approval of  Anzupgo® (delgocitinib) cream (20 mg/g) for the topical treatment of moderate-to-severe chronic hand eczema (CHE) in adults who have had an inadequate response to, or for whom topical corticosteroids are not advisable.1

Anzupgo is an innovative steroid-free, topical pan-Janus kinase (JAK) inhibitor for adults with CHE.1 Anzupgo inhibits the JAK-STAT pathway, specifically blocking the activity of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2), and suppresses the various inflammatory responses that play a key role in the onset and subsequent flares of CHE.1,2,4

The FDA approval of Anzupgo marks a significant milestone in LEO Pharma’s strategy to expand its presence in the U.S. market and deliver purposeful innovation in skin health. In preparation for bringing Anzupgo to the U.S. patients, LEO Pharma has significantly upscaled its operations across key functions – including a 50% increase in the sales force.

“Anzupgo is a good example of how we transform a real need in the market into medicines that can help make a difference for people living with serious skin diseases such as CHE,” said Christophe Bourdon, CEO, LEO Pharma. “After successfully launching Anzupgo in several countries, we’re proud to now bring this innovation to adult patients with moderate-to-severe CHE in the United States. The approval of Anzupgo reinforces our commitment to investing in difficult-to-treat skin conditions to deliver new treatments to patients where the need is greatest. We’re truly grateful to the patients and physicians who participated in our studies and helped make this approval possible.”

CHE is a highly debilitating inflammatory skin disease that affects approximately one in ten adults worldwide, causing itchy, painful, blistered, or swollen skin that can interfere with daily activities.2,3,5,6 The FDA approval of Anzupgo provides adults in the U.S. living with moderate-to-severe CHE with the first and only treatment option specifically approved for this skin disease, just as it will be the first and only topical pan-JAK-inhibitor on the U.S. market.

“Chronic hand eczema can be a very difficult disease for adults to manage, especially given the lack of treatment options in the U.S. until now,” said Robert Spurr, EVP and President, North America, LEO Pharma. “As the first and only FDA-approved treatment specifically for CHE in the U.S., Anzupgo further establishes our company's real commitment to bringing treatments to market that address unmet needs in medical dermatology.”

The FDA approval is the latest regulatory milestone for Anzupgo, following the European Commission (EC) approval in 2024 and several launches internationally, including Germany, Switzerland, the United Kingdom and the United Arab Emirates.

About Anzupgo (delgocitinib) Cream

Anzupgo® (delgocitinib) cream is currently FDA approved in the U.S. as the first and only treatment for chronic hand eczema (CHE). Anzupgo is also approved in the European Union, United Kingdom, Switzerland and the United Arab Emirates for the treatment of moderate-to-severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or not advisable. Anzupgo cream is also under investigation in other markets. Use of Anzupgo in combination with other JAK inhibitors or potent immunosuppressants is not recommended by the U.S. FDA.1

Anzupgo cream is a topical pan-Janus kinase (JAK) inhibitor for the treatment of moderate-to-severe CHE in adults. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE.7

In 2014, LEO Pharma A/S and Japan Tobacco Inc. (JT) entered into a license agreement in which LEO Pharma gained exclusive rights to develop and commercialize delgocitinib for topical use in dermatological indications worldwide, excluding Japan, where JT retains rights.

About Chronic Hand Eczema

Chronic hand eczema (CHE) is defined as hand eczema (HE) that lasts for three or more months or relapses twice or more within a year.5,8 HE is one of the most common skin disorders of the hands and in a substantial number of patients, it can develop into a chronic condition.9 CHE affects approximately one in ten adults worldwide.2,3 It is a fluctuating disorder characterized by itch and pain, and patients may experience signs such as erythema, scaling, lichenification, hyperkeratosis, vesicles, edema, and fissures on hands and wrists.6 The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome.2

CHE has been shown to cause psychological and functional burdens that impact patient quality of life,10,11 with approximately 70% of individuals who live with severe CHE admitting to problems in performing everyday activities.12 Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE

REF: https://en.wikipedia.org/wiki/Delgocitinib

FDA Approves Anzupgo (delgocitinib) Cream for the Treatment of Chronic Hand Eczema

GLP-1 diabetes drugs likely trump metformin for curbing dementia risk in type 2 diabetes, study finds

In continuation of my update  "Metformin"

GLP-1 receptor agonists, a class of drug used to treat type 2 diabetes, likely trump the widely prescribed metformin for curbing dementia risk in people with the condition, finds the largest study of its kind, published in the open access journal BMJ Open Diabetes Research & Care.

The findings suggest that future clinical guidelines for the treatment of type 2 diabetes would do well to consider prioritizing drugs with both blood glucose and neuroprotective effects, say the researchers.

Published research suggests that both GLP-1 receptor agonists and metformin, which are widely used to treat type 2 diabetes, protect the brains of people with the disease. But as yet there have been no direct real-world comparisons of the potential impact of these drugs on dementia risk—a risk that is around 70% higher in people with type 2 diabetes.

To explore this further, the researchers drew on anonymized electronic health records from a global health research network (Trinetx) spanning the period 2004 to 2024 to track the development of dementia in patients with type 2 diabetes, treated with either GLP-1 receptor agonists or metformin (87,229 patients in each group; average age 58) for at least six consecutive months.

There was no significant difference in vascular dementia risk between the two types of drug when used as first line therapy.

But GLP-1 receptor agonist use was associated with a significantly lower cumulative (10%) risk of developing dementia, overall, with an incidence of almost 2.5% (2,130 people) compared with an incidence of nearly 5% (4,215 people) for metformin.

And specifically, taking this type of drug was associated with a 12% lower risk of developing Alzheimer's disease, and a 25% lower risk of developing non-vascular dementias than metformin use.

Further in-depth analyses showed that these positive effects were evident across all age groups, but with the strongest effect among the over 60s, women, and those of white ethnicity.

Risk of death from any cause was also lower: nearly 5% of those treated with GLP-1 receptor agonists died compared with nearly 9% of those treated with metformin.

"Both medications demonstrate neuroprotective properties, such as reducing neuroinflammation and oxidative stress, improving insulin sensitivity, and enhancing cerebrovascular health, which likely contribute to their benefits in overall dementia," explain the researchers.

But unlike metformin, whose benefits primarily derive from systemic metabolic effects, GLP-1 receptor agonists exert direct central nervous system effects by crossing the blood-brain barrier, they add.

"However, the multifactorial nature of [vascular dementia], driven by cerebrovascular damage, such as small vessel disease and white matter lesions, poses significant challenges for pharmacological interventions targeting metabolic or neurodegenerative pathways," they continue.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers point out that the tracking period, while sufficient for observing dementia outcomes, may not fully capture long-term cognitive effects, especially given the progressive nature of Alzheimer's disease.

But they nevertheless conclude, "Given the severe societal, familial, and economic burden of diabetes-related dementia, these findings raise important considerations about the role of GLP-1 [receptor agonists] as first-line therapies in [type 2 diabetes] management.

"While further long-term studies are warranted to validate these results, integrating GLP-1 [receptor agonists] as primary therapeutic agents may represent a paradigm shift in preventing the cognitive complications of diabetes."

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

FDA Approves Ibtrozi (taletrectinib) for Advanced ROS1-Positive Non-Small Cell Lung Cancer

Nuvation Bio Inc. announced the U.S. Food and Drug Administration (FDA)  approval of  Ibtrozi (taletrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC). Ibtrozi is a highly selective, next-generation oral ROS1 tyrosine kinase inhibitor (TKI) designed to address some of the outstanding challenges of treating ROS1+ NSCLC. It has demonstrated high response rates with durable benefit and intracranial activity and is generally well tolerated, providing a new treatment option for patients with advanced ROS1+ NSCLC.

“The FDA approval of Ibtrozi marks a major milestone in the evolution of targeted therapy for advanced ROS1-positive NSCLC,” said David Hung, M.D., Founder, President and Chief Executive Officer of Nuvation Bio. “We believe one of the greatest threats to ROS1-positive lung cancer patients is disease progression, especially in the first-line setting. In pivotal trials, Ibtrozi delivered high response rates with sustained durability—truly meaningful benefits for patients. With its clinically proven efficacy and safety profile, we believe Ibtrozi has the potential to become a new standard for what targeted therapies can achieve in this type of lung cancer. With approvals for Ibtrozi now in the U.S. and China, and additional global filings underway, we remain committed to delivering innovative therapies that help patients stay ahead of their disease.”

ROS1+ NSCLC is a rare and aggressive form of lung cancer, accounting for approximately 2% of new NSCLC cases, or about 3,000 new diagnoses of advanced disease annually in the U.S. The median age at diagnosis for patients with this type of lung cancer is approximately 50 years old, and the disease is more likely to occur in people who have never smoked. Brain metastases are common and a leading cause of disease progression and mortality in this population.

“For people living with advanced ROS1-positive lung cancer, who tend to be diagnosed at a younger age, having another treatment option can make a real difference for them and their loved ones,” said Janet Freeman-Daily, Co-Founder and President of The ROS1ders. “The approval of this new targeted therapy is a meaningful step forward for the advanced ROS1+ lung cancer community and offers hope for patients facing the added challenge of cancer spreading to the brain.”

The FDA approval of Ibtrozi is supported by one of the largest global clinical trial programs in ROS1+ NSCLC to date, with over 300 patients enrolled in the pivotal TRUST-I and TRUST-II studies.

In TRUST-I, Ibtrozi achieved a confirmed overall response rate (cORR) of 90% in TKI-naïve patients. These findings were reinforced by the TRUST-II results, with a cORR of 85% in TKI-naïve patients. The median duration of response (DOR) was not yet reached for either trial, based on a cutoff date that is nearly five months later than that of the pooled TRUST-I and TRUST-II analysis published in April in the Journal of Clinical Oncology. For TRUST-I, with a median follow-up for responses of 40 months, the longest DOR was observed at 46.9 months and ongoing. For TRUST-II, with a median follow-up for responses of 19 months, the longest DOR was observed at 30.4 months and ongoing as of October 2024. Given the single-arm nature of the TRUST clinical studies, median progression-free survival (PFS) is not provided in the label.

Across the pivotal studies, consistent results were also observed among patients who were previously treated with a ROS1 TKI (TKI-pretreated). In TRUST-I, treatment with Ibtrozi achieved a cORR of 52% and median DOR of 13.2 months for TKI-pretreated patients, with median follow-up for responses of 33 months. In TRUST-II, treatment with Ibtrozi achieved a cORR of 62%, and as of October 2024 the median DOR was 19.4 months in these patients, with a median follow-up for responses of 19 months.

Brain metastases are among the most common and devastating complications in advanced ROS1+ NSCLC. Ibtrozi was designed to penetrate the central nervous system (CNS) and has demonstrated consistent intracranial responses in patients with measurable brain metastases at baseline. An intracranial response was achieved in 73% of TKI-naive patients (11/15) and 63% of TKI-pretreated patients (15/24).

“Patients living with advanced ROS1+ non-small cell lung cancer and their healthcare providers are in need of new treatment options,” added Nathan Pennell, M.D., Ph.D., TRUST study investigator and Professor of Medicine at the Cleveland Clinic. “Ibtrozi’s durability of response and ability to effectively penetrate the brain, coupled with a well-characterized and manageable safety profile, further addresses these critical needs for patients. I believe this now-approved therapy offers providers and patients a promising new option for the treatment of advanced ROS1+ non-small cell lung cancer.” Dr. Pennell is a compensated member of Nuvation Bio’s advisory committee.

Ibtrozi was generally well-tolerated, with most adverse events being low grade, transient and manageable. Patients infrequently (7%) discontinued treatment due to treatment-emergent adverse events (TEAEs). The most common adverse reactions (≥20%) included diarrhea (64%), nausea (47%), vomiting (43%), dizziness (22%), rash (22%), constipation (21%), and fatigue (20%). Overall, the majority of CNS events were mild to moderate (~90%) and resolved within days, and dose modifications due to these events were low (~5%). Approximately 90% of reported cases of dizziness were Grade 1 (mild) and transient. Liver enzyme elevations (AST 87%/ALT 85%) and QT prolongation (19%) were manageable with standard monitoring and dose modifications. Ibtrozi is approved as a 600 mg once-daily oral dose, supported by a half-life of approximately 66 hours and broad tissue distribution, including the brain, enabling sustained systemic and CNS exposure.

FDA Approves Ibtrozi (taletrectinib) for Advanced ROS1-Positive Non-Small Cell Lung Cancer

FDA Approves Zusduri (mitomycin) for Recurrent Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer

UroGen Pharma Ltd. announced the U.S. Food and Drug Administration (FDA) approval of  Zusduri, the first and only FDA-approved medication for adults with recurrent LG-IR-NMIBC. Zusduri consists of mitomycin and sterile hydrogel, using UroGen’s proprietary sustained release RTGel® technology. Zusduri has been designed for potent tumor ablation. This landmark approval is based on the positive results from the Phase 3 ENVISION trial that demonstrated Zusduri delivers 78% complete response (CR) for patients at 3 months, and of those patients 79% remained event-free 12 months later.

“The approval of Zusduri represents a significant step forward for our company and for the treatment of recurrent LG-IR-NMIBC," said Liz Barrett, President and CEO of UroGen. "For the first time, the estimated 59,000 U.S. patients facing recurrent LG-IR-NMIBC each year have access to an FDA-approved medicine. This historic achievement is a bold leap forward in our mission to redefine uro-oncology and bring innovation to patients who need it most. We are deeply grateful to the FDA for their collaboration and to the investigators, patients, and caregivers whose commitment made this milestone possible. Their contributions have been essential in bringing meaningful innovation to the bladder cancer community.”

The existing standard of care for LG-IR-NMIBC is a surgical procedure typically performed under general anesthesia called transurethral resection of bladder tumor (TURBT). Due to high recurrence rates of LG-IR-NMIBC, repeat TURBTs may be necessary.

"Zusduri marks a breakthrough in uro-oncology, offering a new alternative for recurrent LG-IR-NMIBC patients who can live for many years with the disease but often endure multiple resections, under general anesthesia,” said Dr. Sandip Prasad, MD, M.Phil., Director of Genitourinary Surgical Oncology at Morristown Medical Center/Atlantic Health System, NJ, and principal investigator of the ENVISION trial. “For decades, TURBT has been the standard approach for bladder cancer treatment. That’s why innovative treatments like Zusduri are essential, especially for those adult patients with recurrent low-grade, intermediate-risk NMIBC.”

The most common (≥ 10%) adverse reactions, including laboratory abnormalities, that occurred in patients were increased creatinine, increased potassium, dysuria, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, increased eosinophils, decreased lymphocytes, urinary tract infection, decreased neutrophils, and hematuria. Serious adverse reactions occurred in 12% of patients who received Zusduri, including, urinary retention (0.8%) and urethral stenosis (0.4%).

REF ;https://en.wikipedia.org/wiki/Mitomycins

FDA Approves Symbravo (meloxicam and rizatriptan) for the Acute Treatment of Migraine with or without Aura in Adults

Axsome Therapeutics, Inc.  announced that the U.S. Food and Drug Administration (FDA) has approval of  Symbravo (meloxicam and rizatriptan) for the acute treatment of migraine with or without aura in adults. Symbravo represents a novel multi-mechanistic approach to treating migraine that targets multiple pathways underlying a migraine attack. Symbravo can rapidly eliminate migraine pain and return patients to normal functioning, with efficacy sustained through 24 and 48 hours in some patients after a single dose. The efficacy of Symbravo was demonstrated across a broad range of settings including at the earliest onset of migraine when the pain was mild, in patients with moderate and severe migraine pain, and in those with a history of various responses to prior acute treatments. The Company expects Symbravo to be commercially available in the U.S. in approximately four months.

Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center, Albert Einstein College of Medicine, commented, “A significant proportion of migraine patients experience inadequate efficacy with currently available acute treatments, leading to even greater suffering, and an increased risk of worsening of migraine pain and attack frequency. Results of multiple clinical trials demonstrate that Symbravo can provide rapid and long-lasting freedom from migraine pain, whether treatment is taken early in the attack while the pain is mild, or later in the attack when the pain may be severe. The approval of Symbravo is a long awaited and much welcomed advancement for clinicians and our patients, providing a new, meaningful treatment option.”

Rizatriptan

meloxicam

Stewart Tepper, MD, Clinical Professor of Neurology at the Geisel School of Medicine at Dartmouth and Vice President of the New England Institute for Neurology and Headache, said, “Migraine is a debilitating condition that affects millions of Americans. Unfortunately, many patients still struggle to find an option that effectively treats their attacks and is both safe and well tolerated, which creates a great need for new migraine medicines. Symbravo’s approval by the FDA provides a new medicine for physicians and patients that was designed to target key unmet needs in the migraine treatment space. The clinical data supporting its approval validates the additive benefit of Symbravo’s multi-mechanistic design and demonstrates its potential to make a meaningful difference for the migraine community.”

Susan Doughty, Executive Director of the Coalition for Headache and Migraine Patients (CHAMP), added, “Migraine is one of the most misunderstood and stigmatized neurological diseases, despite the fact that one in four households in the U.S. includes someone living with it. This widespread lack of understanding creates unnecessary barriers for individuals seeking proper diagnosis, care, and treatment. CHAMP, alongside our 20 plus dedicated coalition organizations and patient advocates, is committed to empowering the migraine community by providing education, reducing stigma, and advocating for fair and equitable access to treatment options. The approval of Symbravo as a new acute treatment for migraine is an important step forward, offering a new option for people seeking relief. We also see this moment as an opportunity to continue to shine a bright light on migraine, fostering greater awareness and helping to dismantle the stigma that so often surrounds this disease.”

The FDA approval of Symbravo is based on the results of the Phase 3 MOMENTUM trial that treated migraine of moderate and severe pain intensity, the Phase 3 INTERCEPT trial that treated migraine when the initial pain was mild, and the Phase 3 MOVEMENT long-term open label safety trial. In this comprehensive clinical program, over 21,000 migraine attacks were treated with Symbravo.

In the MOMENTUM trial, Symbravo demonstrated a statistically significantly greater percentage of patients achieving pain freedom and freedom from their most bothersome symptom (photophobia, phonophobia, nausea) 2 hours after dosing compared to placebo. Symbravo also demonstrated statistical superiority for pain relief (reduction of moderate or severe pain to no pain or mild pain) and the ability to perform normal daily activities. The benefits of pain freedom at 2 hours were sustained through 24 and 48 hours for many patients. In a head-to-head comparison, Symbravo demonstrated statistically significant superiority compared to rizatriptan on sustained pain freedom from 2 to 24 hours. Notably, these benefits were seen with only a single dose of Symbravo. In the MOMENTUM trial, 77% of patients treated with Symbravo did not require rescue medication within 24 hours post dose.

In the INTERCEPT trial, Symbravo demonstrated a statistically significantly greater percentage of patients achieving pain freedom and freedom from their most bothersome symptom (photophobia, phonophobia, nausea) 2 hours after dosing compared to placebo. The benefits of pain freedom at 2 hours were sustained through 24 and 48 hours for many patients. Notably, these benefits were seen with only a single dose of Symbravo. In the INTERCEPT trial, 85% of patients treated with Symbravo did not require rescue medication within 24 hours post dose.

The most common adverse reactions (≥1% and greater than placebo) in the controlled studies were somnolence and dizziness, being reported each in 2% and 1% of patients in the Symbravo and placebo arms, respectively. The long-term safety of Symbravo was demonstrated in the MOVEMENT trial, which assessed 706 patients dosing intermittently for up to 12 months and treating at least 2 migraines per month with Symbravo.

Symbravo is engineered with Axsome’s patented MoSEICTM (Molecular Solubility Enhanced Inclusion Complex) rapid absorption technology. MoSEIC results in a five times faster median time to maximum plasma concentration for meloxicam while maintaining a long plasma half-life, enabling meloxicam’s use as a new molecular entity for the acute treatment of migraine. Symbravo is protected by a robust patent estate extending out to at least 2040.

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

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

FDA Approves Grafapex (treosulfan) Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation

Medexus was informed that the FDA approved Grafapex, an alkylating agent, with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and paediatric patients one year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Grafapex holds Orphan Drug Designation under the Orphan Drug Act, meaning that the product will benefit from up to seven-and-a-half years of regulatory exclusivity in the FDA-approved indication. Medexus holds exclusive commercial rights to Grafapex in the United States under a February 2021 exclusive license agreement with medac GmbH.

"We are pleased to report this positive development, which marks a strategically important step forward for our business and, importantly, will now benefit eligible patients across the United States," commented Ken d'Entremont, Medexus's Chief Executive Officer. "Not only will Grafapex make a substantial contribution to alloHSCT in the United States, but it also solidifies Medexus's leadership position in this therapeutic field."

"We are targeting a commercial launch in the first half of calendar year 2025, and given our recent experience in Canada we are very optimistic about the potential of Grafapex in the US market," added Richard Labelle, Medexus's Chief Operating Officer. "We anticipate that Grafapex will have a meaningful impact on Medexus's total revenue and believe that annual product-level revenue in the United States has the potential to exceed US$100 million within five years after commercial launch."

"This FDA approval provides a useful option for adult and pediatric patients, with the potential to enhance overall survival while minimizing side effects," said Dr Filippo Milano, a stem cell transplant physician-scientist and principal investigator in clinical trials using treosulfan as part of a conditioning regimen.

About Grafapex (treosulfan) for injection

Grafapex (treosulfan) for injection, an alkylating agent, is indicated in combination with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult and pediatric patients one year of age and older with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Grafapex holds Orphan Drug Designation under the Orphan Drug Act, meaning that the product will benefit from a seven-year period of regulatory exclusivity in the FDA-approved indication.

Full prescribing information for Grafapex will be available on the Drugs@FDA drug database at www.fda.gov.

Efficacy was evaluated in MC-FludT.14/L Trial II (NCT00822393), a randomized active-controlled trial comparing treosulfan to busulfan with fludarabine as a preparative regimen for allogeneic transplantation. Eligible patients included adults 18 to 70 years old with AML or MDS, Karnofsky performance status ≥60%, and age ≥50 years or hematopoietic cell transplantation comorbidity index [HCTCI] score >2. There were 570 patients randomized to treosulfan (n=280) or busulfan (n=290).

The major efficacy outcome measure was overall survival (OS), defined as the time from randomization until death from any cause. The hazard ratio for OS (stratified by donor type and risk group) compared to busulfan was 0.67 (95% CI: 0.51, 0.90) in the randomized population, 0.73 (95% CI: 0.51, 1.06) in patients with AML, and 0.64 (95% CI: 0.40, 1.02) in patients with MDS.

The most common adverse reactions (≥20%) were musculoskeletal pain, stomatitis, pyrexia, nausea, edema, infection, and vomiting. Selected Grade 3 or 4 nonhematological laboratory abnormalities were increased GGT (gamma-glutamyl transferase), increased bilirubin, increased ALT (alanine aminotransferase), increased AST (aspartate aminotransferase), and increased creatinine.

The recommended treosulfan dose is 10 g/m2 daily on days -4, -3, and -2 in combination with fludarabine 30 mg/m2 daily on days -6, -5, -4, -3, and -2, and allogeneic hematopoietic stem cell infusion on day 0.

For more information about Grafapex, including important safety information, see the full prescribing information, which will be available on the Drugs@FDA drug database at www.fda.gov. For more information about the pivotal phase 3 clinical trial of treosulfan conducted by medac GmbH, including its methods, results, and conclusions, and about the publication of the study in the American Journal of Hematology, including a link to the full publication, see Medexus's June 6, 2022 press release, including the section entitled "About the study", available on the Investors-News & Events section of Medexus's corporate website.

Grafapex (treosulfan) for injection is approved by the FDA for sale and use in the United States only and is not intended for export outside the United States. Medexus makes no representation that Grafapex (treosulfan) for injection is appropriate for, or authorized for sale to or use by, persons who are not located in the United States.

REF: https://en.wikipedia.org/wiki/Treosulfan