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