FDA Approves Gomekli (mirdametinib) for the Treatment of Adult and Pediatric Patients with NF1-PN

SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced  the U.S. Food and Drug Administration (FDA)   approval of  ™ (mirdametinib), SpringWorks’ MEK inhibitor, for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.1 With the approval, SpringWorks was granted a rare pediatric disease priority review voucher (PRV) by the FDA.

“The NF1-PN patient community has a great need for more treatment options. With today’s approval, we are honored to serve both adults and children with NF1-PN and provide them with a therapy that has the potential to shrink their tumors and offer meaningful symptomatic relief,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We are grateful to each clinical trial participant, their families, the investigators, and the patient advocacy groups involved in the journey towards making Gomekli available in the U.S. I am proud that we are delivering on our commitment to patients with devastating diseases with our company’s second FDA approval in less than 18 months.”

NF1 is a genetic disorder that currently affects approximately 100,000 children and adults in the United States.2,3 Patients with NF1 have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PNs, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment.2,4 There are approximately 40,000 people in the United States living with NF1-PN, the majority of whom are adults that have not had an approved medicine until Gomekli.5 Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, an aggressive and potentially fatal disease.6 Surgical removal can be challenging due to the infiltrative tumor growth pattern of plexiform neurofibromas along nerves, and up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.7,8,9

“Patients with NF1-PN often face significant challenges with their health and have had limited treatment options to manage this devastating condition,” said Christopher Moertel, M.D., Medical Director Pediatric Neuro-Oncology and Neurofibromatosis Programs and Kenneth and Betty Jayne Dahlberg Professor of Pediatrics, University of Minnesota, and lead investigator of the ReNeu trial. “It was very encouraging in the ReNeu trial to see that Gomekli provided deep and durable responses, with a manageable safety profile that enabled patients to stay on therapy. This approval represents an important advance, especially for adults who previously did not have an approved treatment.”

Gomekli was approved under Priority Review and SpringWorks received a rare pediatric disease priority review voucher from the FDA. Gomekli was previously granted Orphan Drug and Fast Track designations for the treatment of NF1-PN.

The FDA approval of Gomekli is based on results from the Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN ≥2 years of age (58 adults and 56 pediatric patients).10 Gomekli met the primary endpoint of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating a 41% ORR (N= 24/ 58) in adults and 52% in children (N=29/56).10 Tumor volume reductions were deep and durable; the median best percentage change in target PN volume was -41% (range: -90 to 13%) in adults and -42% (range: -91 to 48%) in children.10 Eighty-eight percent of adults and 90% of children with a confirmed response had a response of at least 12 months duration, and 50% and 48%, respectively, had a response of at least 24 months duration.10 Patients in both cohorts also experienced early and sustained significant improvements from baseline in pain, and quality of life, as assessed across multiple patient-reported outcome tools.10

Gomekli demonstrated a manageable safety and tolerability profile.1 The most common adverse events (>25%) reported in adults receiving Gomekli were rash, diarrhea, nausea, musculoskeletal pain, vomiting and fatigue.1 The most common adverse events (>25%) occurring in children were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.1 Please see additional Important Safety Information below, including Warnings & Precautions relating to ocular toxicity, left ventricular dysfunction, dermatologic adverse reactions, and embryo-fetal toxicity.1

“We are excited to celebrate the extraordinary milestone of our partners and long-term friends at SpringWorks for the NF1-PN community. This FDA approval shows the power of collaboration to advance innovative science for drugs that may otherwise not have been taken forward,” said Annette Bakker, Ph.D., Chief Executive Officer of the Children’s Tumor Foundation. "When industry, researchers, and organizations like ours driving treatment innovation join forces, scientific progress moves faster, and patients gain access to the therapies they need. Every treatment approval is hard-won, built on research, persistence, and partnership. Today, that work delivers a critical new option for NF patients of all ages.”

“NF1-PN is a complex, devastating disease that affects not only individual patients, but entire families. Treatment advances are crucial to achieving better outcomes for patients and this FDA approval offers hope for NF patients and their families,” said Kim Bischoff, Executive Director, NF Network.

SpringWorks is dedicated to helping patients with NF1-PN access Gomekli and to providing support throughout their treatment journey. The SpringWorks CareConnections™ program is a comprehensive patient support program that offers personalized support services and resources to eligible Gomekli patients, including insurance coverage information and access support, financial assistance and personalized educational and emotional support. Physicians and patients can contact 1-844-CARES-55 (1-844-227-3755) or visit www.springworkstxcares.com for more information.

Gomekli is expected to be available through a specialty pharmacy and specialty distributor network in the United States within two weeks.

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

FDA Approves Gomekli (mirdametinib) for the Treatment of Adult and Pediatric Patients with NF1-PN

FDA Approves Emblaveo (aztreonam and avibactam) for the Treatment of Adults With Complicated Intra-Abdominal Infections

In continuation of update on avibactam 

aztreonam

avibactam

AbbVie (NYSE: ABBV)   announced   the U.S. Food and Drug Administration (FDA)   approval of  Emblaveo™ (aztreonam and avibactam), as the first and only fixed-dose, intravenous, monobactam/β-lactamase inhibitor combination antibiotic. It is approved in combination with metronidazole, for patients 18 years and older who have limited or no alternative options for the treatment of complicated intra-abdominal infections (cIAI), including those caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens. Approval of this indication is based on limited clinical safety and efficacy data for Emblaveo. Gram-negative bacterial infections are among the most challenging for healthcare professionals to control due to high antimicrobial resistance (AMR).2 When AMR develops, medicines intended to treat these infections become ineffective, increasing the risk of morbidity and mortality.2

"The continued evolution of antimicrobial resistance among Gram-negative bacteria has left some patients with little to no treatment options, resulting in extended hospital stays, additional morbidity and death," said James A. McKinnell, M.D., infectious disease specialist, Milefchik-Rand Medical Group, Torrance Memorial Medical Center in Torrance, California. "The approval of Emblaveo provides physicians a much-needed therapeutic option to help address some of the most difficult antimicrobial-resistant pathogens and provides doctors an opportunity to treat patients with these challenging infections."

AMR is considered an urgent global public health threat and could lead to over 39 million deaths worldwide by 2050.1 An estimated 1.14 million deaths globally were attributed to bacterial AMR in 2021 alone.1 If AMR remains unaddressed, minor infections and routine surgical procedures could become life-threatening or fatal.2 The FDA has prioritized the research and development of new medicines to treat AMR and help prevent the spread of infection.3

"As bacteria evolve, industry, government, and clinical experts must work together to ensure that the infectious disease community has the tools to advance public health," said Roopal Thakkar, M.D., executive vice president, research & development, chief scientific officer, AbbVie. "We're proud to offer this important novel treatment option to urgently address the significant threat of antimicrobial resistance."

Emblaveo is a medication that combines two components: aztreonam, a monobactam antibiotic, and avibactam, a β-lactamase inhibitor that protects aztreonam from serine β-lactamase hydrolysis and restores its activity against bacteria that co-produce Metallo-β-lactamases (MBLs) and serine β-lactamases.4 MBLs are a type of enzyme produced by certain bacteria that can become resistant to antibiotics and are on the rise globally.5 The approval of Emblaveo was supported by prior findings regarding the efficacy and safety of aztreonam for the treatment of cIAI.6 It was also supported by clinical trial results from the Phase 3 REVISIT study, which evaluated the efficacy, safety, and tolerability of Emblaveo for the treatment of serious infections due to Gram-negative bacteria, including MBL-producing multidrug-resistant pathogens, for which there are limited or no treatment options.7

In 2019, the FDA granted Qualified Infectious Disease Product (QIDP) Designation and Fast Track Designation for Emblaveo.8 The QIDP Designation provides certain incentives for the development of new antibiotics, including priority review and eligibility for the FDA's Fast Track Designation, and a five-year regulatory exclusivity extension.8 The Fast Track Designation is designed to facilitate the development of and accelerate the review of drugs to treat serious conditions that do not have sufficient treatment options.8

Emblaveo will be available for commercial use in the U.S. in Q3 2025.

About the Phase 3 REVISIT Study7

The Phase 3 REVISIT clinical trial is a randomized, active-controlled, central assessor-blinded, multicenter trial evaluating Emblaveo ± metronidazole versus the combination of meropenem ± colistin in patients with cIAI or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (not an approved indication for Emblaveo). The study enrolled 422 patients across 81 locations globally. The primary endpoint was clinical cure at the test-of-cure visit in the intent-to-treat (ITT) population. Secondary endpoints included 28-day mortality in the ITT population, and safety in patients in the ITT population who received the study drug. The REVISIT trial included 312 hospitalized patients with cIAI that were randomized 2:1 to receive treatment with Emblaveo with metronidazole or meropenem ± colistin for five to 14 days of therapy. The trial was not designed with any formal hypotheses for inferential testing against the active comparator.

FDA Approves Emblaveo (aztreonam and avibactam) for the Treatment of Adults With Complicated Intra-Abdominal Infections

FDA Approves Onapgo (apomorphine hydrochloride) for the Treatment of Motor Fluctuations in Adults with Advanced Parkinson’s Disease

Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, announced the U.S. Food and Drug Administration (FDA) approval of  Onapgo (apomorphine hydrochloride) injection, formerly known as SPN-830, as the first and only subcutaneous apomorphine infusion device for the treatment of motor fluctuations in adults with advanced Parkinson’s disease (PD). Supernus will make Onapgo available in the second quarter of 2025 with a support team of experts, including a robust nurse education program, and access support at launch.

“Continuous subcutaneous apomorphine infusion already has a proven and established 30-year history in Europe, where it has helped deliver more consistent control of motor fluctuations for thousands of patients,” said Rajesh Pahwa, M.D., Laverne and Joyce Rider Professor of Neurology at the University of Kansas School of Medicine, Director of the Movement Disorder Program at The University of Kansas Health System, and a clinical trial investigator for Onapgo. “In a clinical trial in Europe, patients treated with Onapgo experienced a significant reduction in daily OFF time and a similar significant increase in GOOD ON time. Today’s approval of Onapgo means patients in the U.S. who are not responding well to their current treatment regimen, including levodopa, will now have the option of using a small and lightweight wearable device to deliver a continuous infusion without the need for an invasive surgical procedure.”

The approval is based on results from a Phase 3, 12-week, multicenter, parallel-group, double-blind, randomized, placebo-controlled study (N=107) evaluating the efficacy and safety of Onapgo. The primary efficacy endpoint was the mean change in total daily OFF time assessed from baseline to the end of the 12-week treatment period based on patient diaries. The key secondary endpoints were the mean change in daily GOOD ON time, which was defined as ON time without troublesome dyskinesia, and Patient Global Impression of Change (PGIC).1

“Onapgo represents a novel approach for adults with Parkinson’s disease who are experiencing motor fluctuations,” said Jack Khattar, President and CEO of Supernus Pharmaceuticals. “Supernus’ significant experience in CNS has fueled the success of more than eight widely recognized products in CNS and other therapeutic categories. The addition of Onapgo demonstrates our continued commitment to developing novel alternatives to manage Parkinson’s disease and other neurological conditions.”

"As Parkinson’s disease progresses, levodopa treatment often becomes less effective at delivering consistent motor control in part due to GI dysmotility, variable absorption of oral medication, and the resulting pulsatile stimulation of dopamine pathways in the brain," said Stuart Isaacson, M.D., Director of Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida, and a clinical trial investigator for Onapgo. "With Onapgo, the continuous infusion of apomorphine directly stimulates postsynaptic dopamine receptors with no metabolic conversion needed. In addition, the subcutaneous delivery of apomorphine bypasses the GI tract and enters the brain, which can allow for more predictable symptom improvement."

“As the motor symptoms of Parkinson’s disease worsen over time, patients report alternating states between ON when their medication is working, and OFF when it’s not working optimally,” said Andrea Merriam, CEO of the Parkinson & Movement Disorder Alliance. “These on-again, off-again changes are disruptive and can happen at any time, which is why consistent daily control of OFF time is key to improving how patients feel and move. For many, continuous treatment options like Onapgo can help to make days with Parkinson’s more predictable.”

About the Phase 3 Study

During the Phase 3 study, Onapgo significantly reduced the amount of daily OFF time at 12 weeks from baseline (p=0.0114), with Onapgo-treated patients (n=53) experiencing a 2.6-hour reduction compared to placebo (n=51) with 0.9 hours. The reduction in daily OFF time was accompanied by a similar significant increase in daily GOOD ON time (2.8 hours for Onapgo-treated patients compared to 1.1 hours for the placebo group; p=0.0188).1* In addition, numerically greater improvements in daily OFF time and daily GOOD ON time were seen as early as week 1 and were maintained throughout all measured timepoints. Additionally, Onapgo-treated patients more frequently reported improvement in their state of general health compared with placebo-treated patients (PGIC: 79% vs. 24%; p<0.0001). The most common adverse events (≥10% incidence) were infusion-site nodule, nausea, somnolence, infusion-site erythema, dyskinesia, headache, and insomnia.1

About Parkinson’s disease

Nearly one million people in the U.S. and more than 10 million people worldwide are living with Parkinson’s disease, a progressive and chronic neurodegenerative disorder that can cause tremors, muscle rigidity, and difficulty with movement and balance. Patients may also experience dyskinesia, involuntary movements that can significantly interfere with daily activities.2 The disease impacts the central nervous system (e.g., the brain and spinal cord) and the peripheral nervous system, the network of nerves that support the limbs and the organs of the body (e.g., GI system including digestion, respiration, heart function, and blood pressure).3 While there is no known cure for PD, there are treatments available to help reduce symptoms.4 Patients treated with mainstay regimens may experience periods of GOOD ON time when medication treatment is working well, or OFF time when oral levodopa no longer provides symptom benefit and motor symptoms return.5 PD is the second most common neurodegenerative disorder of aging and the most common movement disorder.6

USE

Onapgo is a prescription medicine used to treat motor fluctuations (OFF episodes) in adults with advanced Parkinson’s disease (PD). It is not known if Onapgo is safe and effective in children.

IMPORTANT SAFETY INFORMATION

Do not take Onapgo if you are:

taking certain medicines to treat nausea (ondansetron, granisetron, dolasetron, palonosetron) and alosetron. People taking ondansetron with apomorphine had very low blood pressure and lost consciousness (blacked out).

allergic to apomorphine or to any ingredients in Onapgo including sulfite. Sulfites can cause severe, life-threatening allergic reactions, especially in people with asthma.

Call your healthcare provider or get emergency help right away if you have any of the following symptoms of severe life-threatening allergic reaction:

hives • itching • rash • swelling (eyes, tongue, lips, or mouth) • chest pain • throat tightness • trouble breathing or swallowing.

Before you start using Onapgo, tell your healthcare provider about all of your medical conditions, including:

difficulty staying awake during the daytime • dizziness, fainting spells, or low blood pressure • asthma

allergies to any medicines containing sulfites • heart problems • a history of stroke or other brain problems

kidney problems • liver problems • a mental problem called a major psychotic disorder • drinking alcohol • if you are pregnant or plan to become pregnant, or breastfeeding or plan to breastfeed. It is not known if Onapgo will harm your unborn baby or pass into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription (over-the-counter) medicines, vitamins, and herbal supplements. Onapgo and certain other medicines may affect each other and cause serious side effects.

If you take nitroglycerin under your tongue (sublingual) while using Onapgo, your blood pressure may decrease and cause dizziness. If possible, lie down before taking it and then try to continue lying down for at least 45 minutes after.

What should I avoid while using Onapgo?

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

https://go.drugbank.com/drugs/DB00714

FDA Approves Onapgo (apomorphine hydrochloride) for the Treatment of Motor Fluctuations in Adults with Advanced Parkinson’s Disease

FDA Approves Journavx (suzetrigine), a First-in-Class Treatment for Adults With Moderate-to-Severe Acute Pain

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX)   announced   U.S. Food and Drug Administration (FDA)   approval of  Journavx (suzetrigine), an oral, non-opioid, highly selective NaV1.8 pain signal inhibitor for the treatment of adults with moderate-to-severe acute pain. Journavx is an effective, well-tolerated medicine without evidence of addictive potential indicated for use across all types of moderate-to-severe acute pain.

“Today’s approval is a historic milestone for the 80 million people in America who are prescribed a medicine for moderate-to-severe acute pain each year,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. “With the approval of Journavx, a non-opioid, pain signal inhibitor and the first new class of pain medicine approved in more than 20 years, we have the opportunity to change the paradigm of acute pain management and establish a new standard of care.”

“This is an incredible day for patients and physicians alike who now have an approved non-opioid treatment that delivers effective acute pain relief and a favorable safety profile without addictive potential,” said Jessica Oswald, M.D., M.P.H., Associate Physician in Emergency Medicine and Pain Medicine in San Diego and Vertex Acute Pain Steering Committee Member. “I believe Journavx could redefine the management of pain and become a foundational treatment option for people with all types of moderate-to-severe acute pain, where options aside from opioids have been so desperately needed.”

As part of Vertex’s ongoing commitment to patients, the company has established patient support programs to help ensure that qualified patients can access Journavx. For more information visit Journavx.com.

About Acute Pain

Acute pain is a serious and potentially disabling condition often caused by surgery, accident or injury. Over 80 million Americans are prescribed medicine to treat their moderate-to-severe acute pain every year. Of these, about 40 million are prescribed an opioid. Nearly 10% of acute pain patients treated initially with an opioid will go on to have prolonged opioid use, and about 85,000 patients will develop opioid use disorder annually. Poorly controlled acute pain can lead to reduced quality of life, development of chronic pain, and increased burden on the health care system and society.

About Journavx (suzetrigine)

Journavx (suzetrigine) is a first-in-class, oral, non-opioid, highly selective pain signal inhibitor that is selective for NaV1.8 relative to other NaV channels. NaV1.8 is a voltage-gated sodium channel that is selectively expressed in peripheral pain-sensing neurons (nociceptors), where its role is to transmit pain signals (action potentials). Because Journavx blocks pain signals only found in the periphery, not in the brain, Journavx provides effective relief of pain without the limitations of currently available therapies, including the addictive potential of opioids.

The U.S. Food and Drug Administration approved twice-daily Journavx for the treatment of adults with moderate-to-severe acute pain. Vertex has established a wholesale acquisition cost for Journavx in the United States of $15.50 per 50mg pill.

Vertex is also evaluating suzetrigine in peripheral neuropathic pain (PNP). The company’s Phase 3 pivotal program for suzetrigine in patients with painful diabetic peripheral neuropathy is ongoing, and Vertex plans to advance its pivotal program evaluating suzetrigine in patients with painful lumbosacral radiculopathy pending discussions with regulators.

INDICATION and IMPORTANT SAFETY INFORMATION

INDICATION AND USAGE

Journavx is a prescription medicine used to treat adults with moderate-to-severe short term (acute) pain.

It is not known if Journavx is safe and effective in children.

IMPORTANT SAFETY INFORMATION

Patients should not take Journavx if they take certain medicines that are strong inhibitors of an enzyme called CYP3A. Patients should ask their healthcare providers if they are not sure.

Before taking Journavx, patients should tell their healthcare provider about all of their medical conditions, including if they: have liver problems. People with liver problems may have an increased risk of getting side effects from taking Journavx; are pregnant or plan to become pregnant as it is not known if Journavx will harm an unborn baby. Patients and their healthcare providers should decide if they will take Journavx while they are pregnant, are breastfeeding, or are planning to breastfeed, as it is not known if Journavx passes into breast milk. Patients and their healthcare providers should decide if they will take Journavx while they are breastfeeding.

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking Journavx with certain other medicines may affect the way Journavx and the other medicines work and may increase patients’ risk of side effects. Patients should ask their healthcare provider or pharmacist for a list of these medicines if they are not sure.

Patients should especially tell their healthcare provider if they take hormonal birth control medicine (contraceptives) containing progestins other than levonorgestrel or norethindrone. If they take one of these contraceptives (progestins other than levonorgestrel or norethindrone), they may not work as well during treatment with Journavx. Patients should also use nonhormonal contraceptives such as condoms or use other forms of hormonal birth control during treatment with Journavx and for 28 days after they stop taking Journavx. Medicines that are substrates of the CYP3A enzyme may become less effective during treatment with Journavx. Their healthcare provider may need to adjust the dose of patients’ medicine when starting or stopping Journavx. Patients should know the medicines they take and keep a list of them to show their healthcare provider and pharmacist when they get a new medicine. Patients should not take food or drink containing grapefruit while taking Journavx.

Journavx can cause side effects: The most common side effects for patients treated with Journavx include itching, muscle spasms, increased blood level of creatine phosphokinase, and rash. Journavx may temporarily reduce the chance of females becoming pregnant while on treatment. Patients should talk to their healthcare provider if they have concerns about becoming pregnant. If patients are using contraceptives, continue to use contraceptives during treatment with Journavx. Patients should tell their healthcare provider if they have any side effect that bothers them or that does not go away. These are not all of the possible side effects of Journavx. Patients should call their healthcare provider for medical advice about side effects. Patients may report side effects to the FDA at 1-800-FDA-1088.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple serious diseases and conditions — cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain — and continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1.

https://en.wikipedia.org/wiki/Suzetrigine#:~:text=Concomitant%20use%20of%20suzetrigine%20with%20strong%20CYP3A4%20inhibitors%20is%20contraindicated.

FDA Approves Subvenite (lamotrigine) Oral Suspension for Epilepsy and Bipolar Disorder

OWP Pharmaceuticals announced the U.S. Food and Drug Administration (FDA)  approval of  Subvenite Oral Suspension, the first and only lamotrigine oral suspension in the United States. This innovative formulation will offer treatment options for patients and healthcare providers by offering a flexible, patient-friendly alternative to tablets.

Lamotrigine is widely prescribed, but until now only solid oral dosage forms have been available. Subvenite Oral Suspension is designed for patients who have difficulty swallowing tablets, those who require individualized dosing, or prefer liquid medication formulations.

“The FDA approval of Subvenite Oral Suspension — the first and only lamotrigine oral suspension — represents a significant advancement in patient care,” said Scott Boyer, Founder and President, OWP Pharmaceuticals. “We are proud to bring this much needed treatment option to patients and clinicians, with availability anticipated later in 2025.”

Key Features and Benefits of Subvenite Oral Suspension:

- First and only FDA-approved lamotrigine oral suspension in the U.S.

- Improved accessibility: Suitable for patients with swallowing challenges, those requiring individualized dosing, or those who prefer liquid medication formulations.

- Precision dosing: Liquid formulation allows for dose titration and flexibility.

- Therapeutic reliability: Developed to deliver the expected safety and efficacy profile as lamotrigine tablets (1).

Availability

Subvenite Oral Suspension has been FDA-approved and is expected to be available in the United States later in 2025 through leading distribution channels. Full prescribing information is available at www.owppharma.com.

Indications

Subvenite is indicated for (2):

Epilepsy - adjunctive therapy in patients aged 2 years and older:

• partial-onset seizures

• primary generalized tonic-clonic (PGTC) seizures

• generalized seizures of Lennox-Gastaut syndrome.

Epilepsy - monotherapy in patients aged 16 years and older:

• Conversion to monotherapy in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug.

Bipolar disorder:

• Maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy.

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

FDA Approves Subvenite (lamotrigine) Oral Suspension for Epilepsy and Bipolar Disorder

FDA Approves Inluriyo (imlunestrant) for Adults with ER+, HER2-, ESR1-Mutated Advanced or Metastatic Breast Cancer

Eli Lilly and Company (NYSE: LLY) announced  the U.S. Food and Drug Administration (FDA)  approval of  Inluriyo (imlunestrant, 200 mg tablets), an oral estrogen receptor antagonist, for the treatment of adults with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2–), ESR1-mutated advanced or metastatic breast cancer (MBC) whose disease progressed after at least one line of endocrine therapy (ET). In the Phase 3 EMBER-3 trial, Inluriyo reduced the risk of progression or death by 38% versus ET. Among patients with ESR1-mutated MBC, Inluriyo significantly improved progression-free survival (PFS) versus fulvestrant or exemestane, with a median PFS of 5.5 months vs 3.8 months (HR=0.62 [95% CI: 0.46-0.82]); p-value=0.0008.

Inluriyo is a treatment for ER+, HER2–, ESR1-mutated MBC. Some breast cancers develop ESR1 mutations that can cause estrogen receptors to become overactive and drive cancer growth. Inluriyo binds, blocks, and facilitates the degradation of these receptors, helping to slow disease progression. Its once-daily dosing provides patients with an oral treatment option.

"This therapy reflects our commitment to developing treatments that improve outcomes for people with breast cancer and represents an important step toward advancing innovative, all-oral treatment approaches," said Jacob Van Naarden, executive vice president and president of Lilly Oncology. "We are deeply grateful to the patients, investigators, Lilly team members and clinical care teams who made this advancement possible. This therapy has the potential to make the treatment journey more manageable for those living with breast cancer."

The Inluriyo label contains a warning and precaution for embryo-fetal toxicity.

The FDA approval is based on the results of the EMBER-3 trial in the patient population harboring ESR1-mutated MBC (n=256). Patients received Inluriyo or ET as first-line treatment for MBC following recurrence on adjuvant aromatase inhibitor (AI), +/- prior CDK4/6 inhibitor (21%), or as second-line treatment for MBC following progression on AI, +/- prior CDK4/6 inhibitor (79%).

"This represents an important advancement for patients with ESR1-mutated MBC, a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance," said Komal Jhaveri, M.D., FACP, FASCO, section head of Endocrine Therapy Research and clinical director of Early Drug Development at Memorial Sloan Kettering Cancer Center, and a principal investigator of EMBER-3. "With its demonstrated efficacy, tolerability profile and oral administration, this therapy provides a meaningful alternative treatment option for this patient population."

In EMBER-3, the majority of adverse events (AEs) with Inluriyo were low grade (Grade 1-2) and the most common adverse reactions (≥10%), including laboratory abnormalities, were hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain. In the study, 4.6% of patients permanently discontinued treatment due to AEs. Dose reductions and dose interruptions occurred in 2.4% and 10% of patients, respectively.

"The approval of Inluriyo expands the metastatic breast cancer treatment landscape for patients who test positive for the ESR1 mutation," said Jean Sachs, CEO, Living Beyond Breast Cancer. "Eligible patients will now have access to an additional treatment option, offering them the potential for flexibility in their daily lives and disease management, and—above all—renewed hope for the future."

Inluriyo is also being studied in the ongoing Phase 3 EMBER-4 trial in the adjuvant setting for people with ER+, HER2– early breast cancer (EBC) at increased risk of recurrence, which is enrolling approximately 8,000 patients worldwide.

https://en.wikipedia.org/wiki/Imlunestrant#:~:text=Society%20and%20culture-,Legal%20status,under%20the%20brand%20name%20Inluriyo.

FDA Approves Inluriyo (imlunestrant) for Adults with ER+, HER2-, ESR1-Mutated Advanced or Metastatic Breast Cancer

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