Existing drug, Ulipristal acetate- could reduce breast cancer risk in pre-menopausal women

In continuation of my update on Ulipristat

NYU Langone Health researchers found that a type of cell death caused by a buildup of highly reactive molecules suppresses lung tumor growth.

The process, called ferroptosis, evolved to let the body signal for self-destruction of cells that are overly stressed for various reasons. This includes cancer cells, but they in turn evolved to have mechanisms that counter ferroptosis so they can continue their uncontrolled growth despite the stress it creates.

Published in Nature, the new study showed that an experimental treatment blocked the action in cancer cells of a protein called ferroptosis suppressor protein 1 (FSP1) to reduce by up to 80% tumor growth in mice with lung adenocarcinoma (LUAD).

Lung cancer is the leading cause of cancer death worldwide, with LUAD the most common lung cancer among nonsmokers, making up about 40% of cases.

"This first test of a drug that blocks ferroptosis suppression highlights the importance of the process to cancer cell survival and paves the way for a new treatment strategy," said senior study author Thales Papagiannakopoulos, Ph.D., an associate professor in the Department of Pathology at the NYU Grossman School of Medicine.

Harmful reactions

Ferroptosis kills cells by building up levels of iron, which generates highly reactive molecules formed from oxygen, water, and hydrogen peroxide called reactive oxygen species (ROS).

Important for normal cell signaling, ROS also often cause oxidative stress, a disease mechanism in which ROS oxidize (add oxygen molecules to) delicate proteins and DNA to pull them apart. ROS damage fats making up the outer layers of cells to cause cell death and tissue damage.

For the new study, the research team genetically engineered mice to delete the FSP1 gene in lung cancer cells, which led to increased cancer cell death and significantly smaller tumors.

The team also found that a potent, relatively new drug type, an FSP1 inhibitor called icFSP1, improved overall survival of lung tumor-bearing mice, nearly to the extent seen in mice with lung tumors genetically engineered to lack the FSP1 gene.

Their work also showed that Fsp1 is likely a better target for future drugs than another ferroptosis suppressor, glutathione peroxidase 4 (GPX4), which has been studied longer.

FSP1 was shown in the new study to play a greater role in blocking ferroptosis in lung cancer cells specifically, and a smaller role than GPX4 in normal cell functions (likely fewer side effects). Unlike with GPX4, increased FSP1 levels were also found to track with poorer survival in human LUAD patients.

"Our future research will focus on optimizing FSP1 inhibitors and investigating the potential of harnessing ferroptosis as a treatment strategy for other solid tumors, such as pancreatic cancer," said lead study author Katherine Wu, an MD/Ph.D. student working in the Papagiannakopoulos lab.

"We aim to translate these findings from the lab into novel clinical therapies for cancer patients."

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

Existing drug could reduce breast cancer risk in pre-menopausal women

FDA Issues Complete Response Letter for Biohaven's Vyglxia (troriluzole) New Drug Application for Spinocerebellar Ataxia

Biohaven Ltd. (NYSE: BHVN) ("Biohaven"), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases,  announced  it has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) seeking approval of Vyglxia (troriluzole) for the treatment of spinocerebellar ataxia (SCA).

 

Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven said, "We are extremely disappointed on behalf of patients by this action from the Office of Neuroscience at FDA. Beyond substantial evidence of safety and efficacy, patients with rare diseases also deserve an efficient, fair and flexible regulatory process that aligns with the urgency of their high unmet medical needs. Such an approach has been mandated by Congress to empower the FDA with maximum regulatory flexibility for rare disease. As a company, we are committed to advancing innovative treatments and remain dedicated to SCA patients despite all the challenges associated with pursuing therapies for rare diseases. Real-world evidence is an important research approach to assessing and delivering new therapies for complex rare diseases but, despite FDA policy initiatives supporting such tools, the front-line review divisions are not yet embracing FDA policy for the use of real-world evidence or the application of regulatory flexibility for rare disease."

Jeremy Schmahmann, M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Unit at Massachusetts General Hospital (MGH), added, "Patients with SCA and clinicians who treat them deserve to be heard on this important NDA filing. There is too much at stake for patients. The FDA decision not to listen to disease experts and respect the patient perspective before taking action represents a misstep in the due process, and a failure to deploy regulatory flexibility to evaluate benefit:risk of a medication that has proven to be safe and effective for this rare, debilitating neurodegenerative disease that has no current treatment."

Dr. Coric added, "The development of Vyglxia® (troriluzole) by Biohaven embodies a strong scientific process and deep commitment that is critical to bringing safe and effective treatments to patients with rare diseases like SCA. Our efforts over eight years, included developing the f-SARA scale in collaboration with the FDA and a real-world evidence study in SCA that showed Vyglxia achieved highly consistent, sustained, robust and clinically meaningful treatment effects with a safe, once-daily oral pill that slowed disease progression by 50-70%. The NDA also included data showing Vyglxia reduced the risk of falls and delayed time to becoming wheelchair bound. The leading SCA experts in the United States directly communicated their support of the troriluzole data to the FDA but unfortunately the Office of Neuroscience's inability to collaboratively engage with Biohaven, the patient community and leading experts leave us with concerns about the lack of regulatory flexibility that is being applied for rare, life-threatening conditions. There are a number of common sense solutions and regulatory tools that the Office of Neuroscience could have applied including a fair hearing of the drug's efficacy and safety risks at an Advisory Committee of experts and patients, post-marketing studies, labelling limitations or an accelerated approval pathway. Patients are waiting and the certainty of disease progression for SCA patients far outweighs any residual uncertainty regarding potential design bias or interpretation of study data, especially when the primary outcome measure was achieved in a study protocol and statistical analysis plan that was reviewed by the FDA prior to data analysis. SCA patients deserved approval of Vyglxia and certainly a more balanced interpretation of benefit:risks."

Biohaven remains committed to working with the FDA to find a path forward for its NDA for Vyglxia and plans to meet with the FDA to discuss potential next steps.

Prioritizing Clinical-Stage, Innovative Assets

Biohaven will prioritize resources to focus all its R&D resources on other key programs from its diversified portfolio. Consistent with Biohaven's enduring commitment as a patient-first drug developer, the company's pipeline is focused on a range of disease indications which have limited or no treatment options and are long overdue for therapeutic innovation.

Bruce Car Ph.D., Chief Scientific Officer at Biohaven, commented, "As drug developers we expect setbacks and our diversified portfolio affords us the opportunity to pivot to other key programs. We remain as resilient as ever in following science in order to make a difference in the lives of people with debilitating diseases. Much important work remains, and we are energized and focused on achieving the critical milestones that lie ahead, mindful that days matter and patients are waiting."

Biohaven is initiating strategic portfolio and cost optimization across multiple programs and will focus forward-looking spend on restructuring of business priorities to achieve an approximately 60% reduction in annual direct R&D spend (which excludes personnel and SBC). This may include pausing or delaying non-priority programs to maintain its cash runway to focus on the priority clinical-stage programs over the next year.

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

https://www.drugs.com/nda/vyglxia_251105.html

Combination treatment may help cut lifelong ibrutinib for chronic lymphocytic leukemia patients

In continuation of my update on ibrutinib

Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the Western Hemisphere, affecting approximately 200,000 people in the United States.

A study appearing in Clinical Cancer Research found that adding the investigational antibody ianalumab (VAY736) to ibrutinib (Imbruvica) allowed some patients with CLL to discontinue daily therapy and potentially improve their quality of life.

Ianalumab targets the B-cell activating factor receptor (BAFR) and ibrutinib belongs to a class of therapeutics called Bruton's tyrosine kinase inhibitors (BTKi).

"BTKis have revolutionized CLL treatment, but patients typically stay on them indefinitely and the therapy can cause long-term toxicity," said John C. Byrd, MD, senior author of the study, who was chair of the Department of Internal Medicine at the University of Cincinnati College of Medicine.

Taking ibrutinib serves as a daily reminder of illness, which many patients find psychologically burdensome, added Byrd, who is currently director of the UPMC Hillman Cancer Center and associate vice chancellor for cancer affairs at the University of Pittsburgh School of Medicine.

Byrd, Kerry A. Rogers, MD, associate professor from The Ohio State University, and other investigators tested this treatment approach that could potentially help patients with CLL avoid long-term therapy.

They selected ianalumab because preclinical studies from Byrd's lab demonstrated superior activity in combination with BTKi drugs when tested against CLL.

Ianalumab blocks signals from the BAFR, preventing cancerous B cells from surviving and maturing, and also marks the cells so the natural killer (NK) cells in the immune system can destroy them.

"We tested whether this antibody could eliminate residual disease and even resistant clones, offering patients a chance to come off therapy," Byrd explained.

Byrd and colleagues conducted a Phase I, open-label, multicenter trial enrolling 39 patients who did not have complete remission on ibrutinib or had developed resistance mutations. Participants received intravenous ianalumab every two weeks alongside a standard dose of ibrutinib for up to eight cycles.

The study evaluated safety, tolerability, and antitumor activity, as well as whether the combination could deepen responses enough to discontinue BTKi therapy.

The combination therapy had no dose-limiting toxicities, according to Byrd. Grade 3 or greater adverse events occurred in 41% of patients, primarily low levels of neutrophils. Overall response was nearly 60%, and 43.6% had undetectable measurable residual disease (uMRD) in blood or bone marrow.

Byrd noted that 17 patients were able to stop ibrutinib and remain off therapy for 12 to 24 months. Biomarker analyses indicated that ianalumab enhanced NK and T-cell activation, supporting its proposed mechanism of action.

Thirteen patients had uMRD in both blood and bone, while four patients had uMRD solely in bone, which Byrd noted as deep responses. "Patients who experience deep responses can stop daily medication, a powerful shift that removes the constant reminder of cancer," said Byrd.

"Taking a medicine every day can be a reminder of sickness for patients, so it is very symbolic for patients with blood cancers to be able to go off therapy," Byrd noted.

The findings have important implications for patients living with CLL, Byrd added. Data showed that this approach could help patients avoid the cumulative toxicity associated with lifelong BTKi therapy.

The infection rates in the patients in this trial were lower than those historically reported with single-agent BTKi therapy, suggesting that adding ianalumab did not increase infection risk.

"These results point to potentially using fixed-duration combination therapy to achieve remission and reduce the burden of continuous treatment," Byrd said.

The limitation of this study is the small sample size and lack of long-term follow-up. "A larger trial is needed to confirm whether this approach can become a standard strategy for reducing BTKi treatment duration," said Byrd.

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

Combination treatment may help cut lifelong ibrutinib for chronic lymphocytic leukemia patients

FDA Approves Kygevvi (doxecitine and doxribtimine) for the Treatment of Thymidine Kinase 2 Deficiency

UCB (Euronext Brussels: UCB), a global biopharmaceutical company, today announced that Kygevvi has been granted approval by the U.S. Food and Drug Administration (FDA) for the treatment of adults and pediatric patients living with thymidine kinase 2 deficiency (TK2d), with an age of symptom onset on or before 12 years.1 It is the first and only approved treatment for these patients living with TK2d.

TK2d is an ultra

Doxecitine/doxribtimine

-rare, life-threatening, genetic mitochondrial disease characterized by progressive (worsening over time) and severe muscle weakness (myopathy) with no approved treatment options beyond supportive care until now.2,3,4,5 It is often fatal, with those experiencing initial symptoms on or before the age of 12 years facing a high risk of premature death (often occurring within 3 years after symptom onset).6 It is estimated that the worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people.7

“The approval of doxecitine and doxribtimine represents a pivotal moment for the TK2d community who previously had no FDA-approved treatment options for this rare genetic mitochondrial disease beyond supportive [palliative] care,” said Donatello Crocetta, Chief Medical Officer at UCB. “We extend heartfelt thanks to the patients, families and friends, advocates, healthcare providers and dedicated clinical trial teams who have partnered with us on this important journey.”

“It’s hard to overstate the importance of this FDA approval for those diagnosed with TK2d. This is an ultra-rare disease community in dire need of treatment options. For too long, caregivers and their families have had to endure the burden of this disease," said Kristen Clifford, United Mitochondrial Disease Foundation President and CEO. “Having the first-ever FDA-approved therapy for TK2d in this patient population not only meets a critical medical need - it represents something greater - hope for the future."

“I’ve been studying mitochondrial diseases for more than three decades and have witnessed firsthand the impact TK2d has on patients and their families. We have been waiting for an approved treatment for many years, and this approval marks a significant milestone in how we can support and manage this debilitating condition,” said Dr. Michio Hirano, Professor of Neurology and Chief of the Division of Neuromuscular Medicine at Columbia University Irving Medical Center.

Supporting data

The Kygevvi approval is supported by safety and efficacy data from one Phase 2 clinical study, two retrospective chart review studies, and an expanded access use program*.1,8,9,10,11 These studies included a total of 82 unique patients treated with Kygevvi or pyrimidine nucleosides with an age of TK2d symptom onset ≤12 years. Efficacy was assessed by comparing overall survival in these pediatric and adult treated patients to an external control group of untreated patients who were matched to treated patients using age of TK2d symptom onset (≤ 2 years or >2 to ≤ 12 years).1 A total of 78 matched pairs were identified. The results showed that survival time from treatment start was improved; treatment reduced the overall risk of death from treatment start by approximately 86% (95% CI: 61%, 96%).1 Of the 78 treated patients included in the survival analysis, the median age of TK2d symptom onset was 1.5 years (range: 0.01 to 12 years).1 The median duration of treatment was 4 years (range: 1 day to 12 years) and the median dose received was 762 mg/kg/day (range: 260 to 800 mg/kg/day).1

The most common adverse reactions (incidence ≥5%) are diarrhea, abdominal pain (including abdominal pain upper), vomiting, alanine aminotransferase increased (ALT), and aspartate aminotransferase increased (AST).1

A regulatory review of doxecitine and doxribtimine is currently underway by the EMA (European Medicines Agency), and further regulatory submissions are planned. Kygevvi is currently not approved for use in any indication by any regulatory authority outside of the U.S. UCB expects Kygevvi to be commercially available in the U.S. in Q1, 2026. To further its mission of equitable care, UCB will provide a personalized support program for Kygevvi that places the needs of patients and caregivers at the forefront.

In the U.S., Kygevvi received Orphan Drug, Breakthrough, Priority Review and Rare Pediatric Disease designations from the FDA.12,13 With this approval by FDA, UCB was awarded a Rare Pediatric Disease Priority Review Voucher (RPDPRV) redeemable for a priority review for a future marketing application.

About Kygevvi

Kygevvi is a combination of doxecitine and doxribtimine, both pyrimidine nucleosides, indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients with an age of symptom onset on or before 12 years.1 Administration of Kygevvi is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial DNA.1 This action restores mitochondrial DNA copy number in TK2d mutant mice.1

Important safety information for Kygevvi1

Increase in Liver Transaminases

Elevated liver transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels were reported in patients treated with Kygevvi. Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in patients prior to treatment initiation with Kygevvi. If signs or symptoms consistent with liver injury are observed, interrupt treatment with Kygevvi until liver transaminase (ALT, AST) and total bilirubin levels have either returned to baseline or stabilized at a new baseline value. Consider permanently discontinuing Kygevvi if signs or symptoms consistent with liver injury persist or worsen. Monitor liver transaminases and total bilirubin levels yearly and as clinically indicated.

Gastrointestinal Adverse Reactions

Diarrhea and vomiting leading to hospitalization, dose reduction, and permanent discontinuation were reported in patients treated with Kygevvi. Based on the severity of the diarrhea and/or vomiting, reduce the dosage of Kygevvi or interrupt treatment until diarrhea and/or vomiting improves or returns to baseline. Consider restarting Kygevvi at the last tolerated dose, and increase the dose as tolerated. For persistent or recurring diarrhea and/or vomiting, consider discontinuing Kygevvi permanently and provide supportive care with electrolyte repletion as clinically indicated.

https://en.wikipedia.org/wiki/Doxecitine/doxribtimine

FDA Approves Kygevvi (doxecitine and doxribtimine) for the Treatment of Thymidine Kinase 2 Deficiency

FDA Approves Epioxa (riboflavin 5’-phosphate) Ophthalmic Solution for the Treatment of Keratoconus

Glaukos Corporation, an ophthalmic pharmaceutical and medical technology company focused on novel therapies for the treatment of glaucoma, corneal disorders, and retinal diseases, announced  the U.S. Food and Drug Administration (FDA) approval of its Epioxa™ HD / Epioxa™ (“Epioxa”) New Drug Application (NDA). Epioxa is a groundbreaking advancement in corneal cross-linking for the treatment of keratoconus, a rare, sight-threatening disease that is currently far too often undiagnosed and untreated.

Epioxa represents a transformative innovation in keratoconus care, offering an incision-free alternative to traditional corneal cross-linking procedures as it does not require the removal of the corneal epithelium, the outermost layer of the front of the eye. This novel, oxygen-enriched topical therapeutic, bioactivated by UV light, is designed to eliminate the pain associated with removal of the epithelium, streamline the procedure, and minimize recovery, all while delivering clinically meaningful outcomes and exceptional value to patients, providers, and the healthcare system. Epioxa is based on two formulations, Epioxa HD and Epioxa, that are sequentially administered during the cross-linking procedure followed by UV activation in an oxygen-enriched environment.

“The FDA approval of Epioxa ushers in a new standard-of-care for patients suffering from keratoconus with the first FDA-approved topical drug therapy that does not require removal of the corneal epithelium,” said Thomas Burns, Glaukos chairman and chief executive officer. “Epioxa is designed to significantly improve patient comfort and minimize recovery time, representing a game-changing new treatment for patients suffering from keratoconus. We appreciate the clinical investigators and study participants in the clinical trials for their instrumental roles in helping us reach this important advancement. This approval marks a major milestone in our mission to improve patient access to sight-saving therapies, and we are excited to bring this transformative therapy to market for the benefit of patients.”

“Keratoconus is currently an underdiagnosed and undertreated disease. For keratoconus patients who are fortunate enough to be diagnosed, the current standard-of-care requires removal of the epithelium, the top layer of the cornea. The pain and extended healing time associated with the current surgical procedure are major barriers to adoption,” said W. Barry Lee, MD, corneal specialist at Eye Consultants of Atlanta and President of the Cornea Society. “As an incision-free treatment that does not require removal of the epithelium, I expect the newly approved Epioxa treatment to address both of these major concerns.”

The FDA approval of Epioxa is based on results from two prospective, randomized, multicenter, double-masked, Phase 3 pivotal trials that randomized a total of over 400 patients. Both trials successfully achieved their pre-specified primary efficacy endpoints and demonstrated favorable tolerability and safety profiles.

Glaukos intends for Epioxa to be commercially available in the first quarter of 2026. With this approval, Glaukos plans to make substantial investments in patient awareness and access while addressing the longstanding challenges of underdiagnosis and undertreatment that have affected this rare disease patient community. These efforts will be focused on supporting patients and families across every step of the journey, from awareness to diagnosis and treatment. Key initiatives include streamlined patient access support programs, a co-pay assistance program to reduce financial barriers, integrated healthcare professional (HCP) and patient-centric strategies to improve education and engagement, and broad awareness and detection programs aimed at earlier and more widespread screening for and diagnosis of the disease.

Keratoconus is a debilitating eye condition characterized by progressive thinning and weakening of the cornea that is often most aggressively advancing in patients under the age of 30. If left untreated, keratoconus can lead to loss of visual function and even blindness and is one of the leading causes of corneal transplants (penetrating keratoplasty) in the United States. Approximately 90% of cases of keratoconus are bilateral and as many as 20% of untreated keratoconus patients ultimately require a corneal transplant. Conventional keratoconus treatments such as eyeglasses or contact lenses address visual symptoms only and do not slow or halt underlying disease progression.

Glaukos’ first-generation corneal cross-linking therapy, known as Photrexa® Viscous / Photrexa®, which requires removal of the corneal epithelium, received U.S. FDA approval in 2016 as an orphan drug and has since been the first-and-only FDA-approved corneal cross-linking therapy for the treatment of keratoconus. There are more than 300 peer-reviewed publications supporting the performance and safety of Glaukos’ cross-linking therapies.

For more information about Epioxa HD / Epioxa and Full Prescribing Information, please visit www.Epioxa.com.

FDA Approves Epioxa (riboflavin 5’-phosphate) Ophthalmic Solution for the Treatment of Keratoconus

FDA Approves Contepo (fosfomycin) for Injection for the Treatment of Complicated Urinary Tract Infections

In Continuation of my update on fosfomycin

The U.S. Food and Drug Administration (FDA) has approved Contepo (fosfomycin) for injection for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI), including acute pyelonephritis, caused by susceptible isolates of Escherichia coli and Klebsiella pneumoniae.

Contepo is an epoxide antibacterial that works by disrupting bacterial cell wall synthesis through covalently binding and inhibiting phosphoenolpyruvate transferase (MurA), thereby blocking the synthesis of peptidoglycan. The drug is bactericidal against Enterobacterales.

Dosing and Administration

The recommended dosage of Contepo is 6 grams administered every 8 hours by intravenous infusion over 1 hour in patients 18 years of age or older with an estimated creatinine clearance greater than 50 mL/min. The duration of therapy is up to 14 days and should be guided by the severity of infection and the patient's clinical status. Dosage adjustments are required for patients with renal impairment.

Clinical Trial Results

The FDA approval was based on data from a multinational, double-blind clinical trial (Trial 1) that enrolled 464 adults hospitalized with cUTI, including acute pyelonephritis. The study compared Contepo 6 grams intravenously every 8 hours to piperacillin/tazobactam 4.5 grams intravenously every 8 hours for 7 days of therapy, with treatment allowed for up to 14 days in bacteremic patients.

In the microbiological modified intent-to-treat (mMITT) population of 339 patients, Contepo demonstrated efficacy with regard to overall response at the test-of-cure visit. Overall success, defined as clinical cure plus microbiological eradication, was achieved in 63.5% (108/170) of Contepo-treated patients compared to 55.6% (94/169) of piperacillin/tazobactam-treated patients.

Important Safety Information

The most common adverse reactions (incidence ≥2%) observed in clinical trials were transaminase elevations, hypokalemia, neutropenia, nausea, vomiting, diarrhea, hypocalcemia, hypernatremia, headache, and hypophosphatemia.

Contepo contains 1,980 mg of sodium in each vial. The high sodium load associated with its use may result in changes in serum electrolytes, such as increased levels of serum sodium and decreased levels of potassium, calcium, and phosphorus. A low-sodium diet is recommended during Contepo treatment, and healthcare providers should monitor serum electrolyte levels and fluid status during treatment.

Contepo has been shown to prolong the QT interval in some patients and should be avoided in patients with known QT prolongation or ventricular arrhythmias, including a history of torsade de pointes. Healthcare providers should monitor electrolytes during treatment with Contepo.

Contepo is contraindicated in patients with known serious hypersensitivity to fosfomycin or any of the excipients.

Postmarketing Requirements

As part of the approval, the FDA has required Meitheal Pharmaceuticals to conduct postmarketing studies, including:

Pediatric pharmacokinetic and safety studies in children from birth to less than 18 years of age

A clinical lactation study to determine fosfomycin concentrations in human milk

A five-year U.S. surveillance study to monitor resistance or decreased susceptibility to fosfomycin in target bacterial populations.

About Complicated Urinary Tract Infections

Complicated urinary tract infections are infections of the urinary tract that occur in patients with structural or functional abnormalities of the urinary tract or with underlying diseases that increase the risk of acquiring infection or failing therapy. Acute pyelonephritis is a severe form of urinary tract infection involving the kidney.

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

FDA Approves Contepo (fosfomycin) for Injection for the Treatment of Complicated Urinary Tract Infections

FDA Approves Contepo (fosfomycin) for Injection for the Treatment of Complicated Urinary Tract Infections

The U.S. Food and Drug Administration (FDA) has approved Contepo (fosfomycin) for injection for the treatment of patients 18 years of age and older with complicated urinary tract infections (cUTI), including acute pyelonephritis, caused by susceptible isolates of Escherichia coli and Klebsiella pneumoniae.

Contepo is an epoxide antibacterial that works by disrupting bacterial cell wall synthesis through covalently binding and inhibiting phosphoenolpyruvate transferase (MurA), thereby blocking the synthesis of peptidoglycan. The drug is bactericidal against Enterobacterales.

Dosing and Administration

The recommended dosage of Contepo is 6 grams administered every 8 hours by intravenous infusion over 1 hour in patients 18 years of age or older with an estimated creatinine clearance greater than 50 mL/min. The duration of therapy is up to 14 days and should be guided by the severity of infection and the patient's clinical status. Dosage adjustments are required for patients with renal impairment.

Clinical Trial Results

The FDA approval was based on data from a multinational, double-blind clinical trial (Trial 1) that enrolled 464 adults hospitalized with cUTI, including acute pyelonephritis. The study compared Contepo 6 grams intravenously every 8 hours to piperacillin/tazobactam 4.5 grams intravenously every 8 hours for 7 days of therapy, with treatment allowed for up to 14 days in bacteremic patients.

In the microbiological modified intent-to-treat (mMITT) population of 339 patients, Contepo demonstrated efficacy with regard to overall response at the test-of-cure visit. Overall success, defined as clinical cure plus microbiological eradication, was achieved in 63.5% (108/170) of Contepo-treated patients compared to 55.6% (94/169) of piperacillin/tazobactam-treated patients.

Important Safety Information

The most common adverse reactions (incidence ≥2%) observed in clinical trials were transaminase elevations, hypokalemia, neutropenia, nausea, vomiting, diarrhea, hypocalcemia, hypernatremia, headache, and hypophosphatemia.

Contepo contains 1,980 mg of sodium in each vial. The high sodium load associated with its use may result in changes in serum electrolytes, such as increased levels of serum sodium and decreased levels of potassium, calcium, and phosphorus. A low-sodium diet is recommended during Contepo treatment, and healthcare providers should monitor serum electrolyte levels and fluid status during treatment.

Contepo has been shown to prolong the QT interval in some patients and should be avoided in patients with known QT prolongation or ventricular arrhythmias, including a history of torsade de pointes. Healthcare providers should monitor electrolytes during treatment with Contepo.

Contepo is contraindicated in patients with known serious hypersensitivity to fosfomycin or any of the excipients.

FDA Approves Contepo (fosfomycin) for Injection for the Treatment of Complicated Urinary Tract Infections

FDA Approves Javadin (clonidine hydrochloride) Oral Solution for the Treatment of Hypertension

In continuation of my update on Clonidine

Azurity Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) approval of  Javadin (clonidine hydrochloride) oral solution, the only FDA-approved, immediate-release, ready-to-use oral liquid clonidine formulation for the treatment of hypertension in adult patients to lower blood pressure. Lowering blood pressure has been shown to reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

“Javadin marks a significant advancement for patients and providers managing hypertension,” said Ronald Scarboro, CEO of Azurity Pharmaceuticals. “The ready-to-use oral solution may streamline hypertension care for some patients who have difficulty swallowing capsules or tablets, eliminating the need for tablet cutting, compounding, or applying a transdermal delivery system. Azurity specializes in delivering innovative, ready-to-use solutions that help to simplify dosing and improve accessibility.”

A recent study found that more than a third of adult primary care patients questioned had difficulty swallowing tablets and capsules, and 58.8 percent of them modified their medications—by splitting, crushing, or opening capsules—potentially compromising efficacy and safety.1

“Javadin lowers blood pressure within 30-60 minutes,” added Ajay Singh, Chief Scientific Officer at Azurity Pharmaceuticals. “Unlike many antihypertensive agents that act peripherally, Javadin works centrally by stimulating alpha-adrenoreceptors in the brain, resulting in decreased peripheral and renal vascular resistance, lower heart rate, and reduced blood pressure.”2

Javadin is a berry-flavored, clear, colorless oral solution. Each 5 mL delivers 0.1 mg of clonidine (0.02 mg/mL). Javadin may be used alone or in combination with other antihypertensive agents. Javadin should not be used in patients with known hypersensitivity to clonidine.

Javadin is expected to be available by end of year 2025.

IMPORTANT SAFETY INFORMATION

Javadin (clonidine hydrochloride) oral solution

Indication and Usage

Javadin is indicated for the treatment of hypertension in adult patients, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. There are no controlled trials demonstrating risk reduction with Javadin.

Javadin may be employed alone or concomitantly with other antihypertensive agents.

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

FDA Approves Javadin (clonidine hydrochloride) Oral Solution for the Treatment of Hypertension

FDA Approves Lynkuet (elinzanetant) for Moderate to Severe Hot Flashes Due to Menopause

Bayer announced  the U.S. Food and Drug Administration (FDA) approval of  Lynkuet® (elinzanetant) 60mg capsules, the first and only dual neurokinin (NK) targeted therapy,1 neurokinin 1 (NK1) and neurokinin 3 (NK3) receptor antagonist, for the treatment of moderate to severe hot flashes due to menopause.1 Inhibition of Substance P and Neurokinin B through antagonism of NK1 and NK3 receptor signaling on kisspeptin/neurokinin B/dynorphin (KNDy) neurons can modulate neuronal activity in the thermoregulation associated with hot flashes.1 Lynkuet soft gel capsules are taken once daily at bedtime, with or without food.1 The FDA approval is supported by data from three Phase III clinical trials (OASIS 1, OASIS 2 and OASIS 3) that evaluated the safety and efficacy of Lynkuet for the treatment of moderate to severe hot flashes due to menopause.

The FDA approval of Lynkuet is an important new option for women and providers who are treating moderate to severe hot flashes due to menopause. As a global leader in women’s healthcare with more than 100 years of research and experience, we are proud to bring this new treatment option to market for women who are going through menopause and seeking hot flash relief.

The efficacy of Lynkuet for the treatment of moderate to severe hot flashes due to menopause was demonstrated in the first 12 weeks of two randomized, double-blind, placebo-controlled, multicenter clinical trials, OASIS 1 and OASIS 2, in 796 menopausal women.1 The co-primary efficacy endpoints in both trials were the mean change in frequency and severity of moderate to severe hot flashes from baseline to weeks 4 and 12, including day and night hot flashes.1 The safety of Lynkuet was evaluated in three randomized, double-blind, placebo-controlled, multicenter clinical trials (OASIS 1, OASIS 2 and OASIS 3) in 1,420 women.1 In OASIS 3, 627 women received Lynkuet or placebo for up to 52 weeks to evaluate long-term safety.1

It’s important to know that women who are pregnant should not take Lynkuet. Lynkuet can cause serious side effects, including central nervous system effects and daytime impairment, increased liver blood test values, risk of pregnancy loss, and risk of seizures in people with a history of seizures. The common side effects of Lynkuet include headache, fatigue, dizziness, feeling drowsy or sleepy, stomach (abdominal) pain, rash, diarrhea, and muscle spasms.1 For more information, please see “Important Safety Information” below.

“These studies investigated the safety and efficacy of elinzanetant for the treatment of moderate to severe hot flashes due to menopause,” said JoAnn Pinkerton, M.D., Professor and Director of Midlife Health at UVA Health and Lead Investigator on the OASIS 2 trial. “Hot flashes, particularly when severe, can have an impact on women’s daily lives and this approval provides healthcare providers with a new treatment option that can be used first-line for moderate to severe hot flashes due to menopause.”

“It’s important that women know they have choices for treating moderate to severe hot flashes due to menopause, and today’s approval further expands a woman’s options for treating these symptoms,” said Claire Gill, President and Founder of the National Menopause Foundation.

As a leader in women’s healthcare, Bayer is committed to making Lynkuet accessible. Through the Lynkuet Access Savings & Support program (LASS), women can connect with a healthcare provider and receive their Lynkuet prescription from home and at the lowest cost available to them. Visit Lynkuet.com to learn more about how to save on Lynkuet. If a patient cannot afford their prescription, Bayer may be able to help. Eligible patients may receive their Bayer prescription medicine at no cost through the Bayer U.S. Patient Assistance Foundation. For more information, please visit www.patientassistance.bayer.us or call to speak with a member of Bayer’s team at 1-866-2BUSPAF (228-7723).

Lynkuet is expected to be available in the U.S. beginning in November 2025. Elinzanetant is approved under the brand name LynkuetTM in Australia, Canada, the United Kingdom and Switzerland. It is pending approval in the European Union and under review in other markets around the world.

INDICATION

What is Lynkuet® (elinzanetant)?

Lynkuet is a prescription medicine used to reduce moderate to severe hot flashes (also known as vasomotor symptoms) due to menopause. Lynkuet is not a hormone. Hot flashes are feelings of warmth in the face, neck, and chest, or sudden intense feelings of heat and sweating.

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

FDA Approves Lynkuet (elinzanetant) for Moderate to Severe Hot Flashes Due to Menopause

FDA Grants Accelerated Approval to Forzinity (elamipretide hydrochloride) for the Treatment of Barth Syndrome

In continuation of mu update on elamipretide

Stealth BioTherapeutics Inc. (the “Company” or “Stealth”),  announced  the U.S. Food and Drug Administration (FDA) accelerated approval of  Forzinity™ (elamipretide HCl) to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kilograms (kg) (approximately 66 pounds). Barth syndrome is a life-limiting pediatric mitochondrial cardioskeletal disease that affects approximately 150 individuals in the United States.

“The approval of Forzinity, the first treatment option for Barth syndrome and the first approved mitochondria-targeted therapeutic, is a pivotal victory for the Barth syndrome community and offers hope for expedited regulatory attention to other ultra-rare diseases,” said Reenie McCarthy, Stealth’s Chief Executive Officer. “We appreciate the FDA’s close engagement in recent months and are grateful to the trial participants, caregivers, advocates, researchers and healthcare providers who persevered in partnership with us over this decade-long journey. We plan to continue providing expanded access to children weighing less than 30 kilograms who are currently receiving treatment or require emergency access, while we work with the FDA to generate data needed to expand the indication to include these children. We are committed to the continued development of therapies to treat all patients with Barth syndrome and other devastating diseases of mitochondrial dysfunction.”

The approval of Forzinity is supported by the efficacy and safety data from the TAZPOWER clinical trial. During the open-label portion of the TAZPOWER trial, knee extensor muscle strength improved from study baseline. The most common adverse reactions were injection site reactions which can be treated with oral antihistamines or topical corticosteroids. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial.

This decision follows months of collaborative dialogue with the FDA to resolve the final regulatory milestones following Stealth’s May 2025 receipt of a complete response letter from the FDA. The approval reflects a shared commitment to ensuring timely access for patients facing this devastating disease. Many of these patients and their families, along with their healthcare providers, have worked tirelessly to educate the FDA about the significant burden of this ultra-rare disease.

“We are grateful that FDA leadership has listened to our community and approved Forzinity for some of our population. Barth syndrome patients live every day with progressively diminishing quality of life,” said Kate McCurdy, Board Chair of the Barth Syndrome Foundation whose son passed away from the disease at age 28. “I witnessed the terrible toll this disease took every day of my son’s life and the many serious medical challenges that ensued. Our patients and their physicians have seen the truly positive impact Forzinity can have on the devastating muscle weakness that restricts daily activities. While we celebrate this critical milestone, we are deeply aware that only half of our patients survive long enough to weigh the 30 kilograms they must in order to be eligible for this treatment now. Therefore, we deeply appreciate Stealth’s pledge to work closely with the FDA on prompt and broad label expansion, so that our youngest and most vulnerable patients can also gain access to this therapy.”

“I am thrilled to have an FDA-approved treatment to offer to patients with Barth syndrome, who often face serious manifestations including severe muscle weakness,” said Hilary Vernon, M.D., Ph.D., Professor of Genetic Medicine at Johns Hopkins University School of Medicine and Founder and Director of the Barth Syndrome Clinic at the Kennedy Krieger Institute. “As the director of one of only two interdisciplinary Barth syndrome clinics worldwide, I have the privilege of interacting with a large percentage of the Barth community in the U.S. and around the world, and I am grateful to have a new therapeutic option available for patients living with Barth syndrome. I look forward to chairing the Trial Scientific Review Committee for the post-marketing trial as I know there is tremendous interest in participation from patients around the world.”

Forzinity received Orphan Drug, Fast Track, Priority Review, and Rare Pediatric Designations from the FDA and Orphan Drug Designation from the European Medicines Agency (EMA) for the treatment of Barth syndrome. In connection with the approval, Stealth has been granted a Rare Pediatric Disease Priority Review Voucher from the FDA.

The approval is limited to children and adults weighing at least 30 kg. Stealth intends to work with the FDA on a plan to collect additional data in children weighing less than 30 kg and to qualify its preservative-free formulation used in expanded access for newborns. Pending potential label expansion and qualification of the preservative-free formulation, Stealth will continue to provide compassionate use access for patients weighing less than 30 kg currently enrolled in its expanded access program or for whom emergency access is necessary.

Stealth is committed to ensuring uninterrupted access for all current patients living with Barth syndrome. Stealth plans to work with payers and providers to ensure timely and equitable access to Forzinity, which it expects will be available for prescriptions in the United States through a specialty pharmacy by year-end. Stealth expects to announce its patient support and access initiatives in the coming weeks.

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

FDA Grants Accelerated Approval to Forzinity (elamipretide hydrochloride) for the Treatment of Barth Syndrome

FDA Approves Wayrilz (rilzabrutinib) for Immune Thrombocytopenia

The US Food and Drug Administration (FDA) has approved Wayrilz (rilzabrutinib) for adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The approval was based on the pivotal LUNA 3 phase 3 study, in which Wayrilz met the primary and secondary endpoints, showing a positive impact on sustained platelet counts and other ITP symptoms.

“The burden of immune thrombocytopenia can be both physical and emotional with significant overlooked symptoms that can impact various aspects of daily living,” said Caroline Kruse, President and CEO at the Platelet Disorder Support Association. “We are pleased to have a new treatment option that can help ease the ongoing strain of managing the disease for patients and their families."

As a novel oral, reversible, Bruton’s tyrosine kinase (BTK) inhibitor, Wayrilz can help address the root causes of ITP through multi-immune modulation, targeting different pathways across the immune system.

“With its differentiated mechanism of action, Wayrilz has the potential to become a treatment of choice for immune thrombocytopenia patients who have not responded to a prior therapy,” said Brian Foard, Executive Vice President, Head of Specialty Care at Sanofi. “Its multi-immune modulation approach shows promise in addressing the key drivers of immune thrombocytopenia, which aligns with Sanofi's commitment to adapting and evolving therapeutic solutions to help tackle ongoing unmet patient needs. This approval underscores Sanofi's expertise and ambitions at the junction of rare and immunological disease."

The LUNA 3 phase 3 study, presented at the 66th American Society of Hematology Annual Meeting and Exposition, evaluated the efficacy and safety of Wayrilz compared to placebo in adults (n=202) with persistent or chronic ITP. Patients who achieved platelet count response at 12 weeks were eligible to continue the full 24-week double-blind period (64% of patients in the Wayrilz arm and 32% of patients in the placebo arm). Patients receiving Wayrilz experienced the following compared to patients receiving placebo:

Statistically significant durable platelet response at week 25 (23% of patients in Wayrilz arm vs. 0% in placebo arm; p<0.0001)

Faster time to first platelet response (36 days in Wayrilz arm vs. not reached in placebo arm; p<0.0001)

Longer duration of platelet response (least square mean of 7 weeks in Wayrilz arm vs. 0.7 weeks in placebo arm)

Patients receiving Wayrilz reported an overall 10.6-point improvement across nine health-related quality of life measures compared to a 2.3-point increase in the placebo arm, based on The Immune Thrombocytopenia Patient Assessment Questionnaire, a clinical tool designed to measure ITP symptoms. The results of this analysis are descriptive and were not powered for statistical significance.

The most common adverse reactions (incidence ≥10%) are diarrhea, nausea, headache, abdominal pain, and COVID-19.

“Traditionally, immune thrombocytopenia management has focused on restoring platelet counts and reducing bleeding risk, which for some patients may result in suboptimal responses, persistent symptoms, or unacceptable treatment complications,” said David Kuter, MD, Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, study author. “Through multi-immune modulation, Wayrilz can offer a new option for patients, including those who fail steroids or do not respond to existing treatment.”

Wayrilz was approved in the United Arab Emirates for adult patients with persistent or chronic ITP who have had an insufficient response or intolerance to a previous treatment in June 2025. Wayrilz is currently under regulatory review for ITP in the EU and China.

It received Fast Track and Orphan Drug Designations (ODD) from the FDA for ITP, with similar orphan designations in Japan and the EU. Most recently, the FDA granted Wayrilz ODD for three additional rare diseases, including warm autoimmune hemolytic anemia (wAIHA), IgG4-related disease (IgG4-RD), and sickle cell disease (SCD). Wayrilz also received FDA Fast Track Designation and European Medicines Agency orphan designation in IgG4-RD.

Wayrilz patients will have access to Sanofi’s HemAssist patient support program that offers assistance for all treatments within Sanofi’s rare blood disorder portfolio. HemAssist aims to help patients and their caregivers with the support they need throughout their treatment journey, including navigation of access and insurance coverage, determining eligibility for financial assistance programs, and providing educational resources. Patient costs for treatment will vary based on insurance and patients without insurance coverage can work with HemAssist to identify potential options by visiting https://www.sanofihemassist.com or by calling 1-833-723-5463.

About the LUNA 3 study

LUNA 3 (clinical study identifier: NCT04562766) was a randomized, multicenter, phase 3 study evaluating the efficacy and safety of Wayrilz vs. placebo in adult and adolescent patients with persistent or chronic ITP. Patients received either oral Wayrilz 400 mg twice a day or placebo through a 12- to 24-week double-blind treatment period, followed by a 28-week open-label treatment period, and then a 4-week safety follow-up or long-term extension period. The adolescent part of the study is ongoing. The primary endpoint is durable platelet response, defined as the proportion of participants able to achieve platelet counts at or above 50,000/μL for more than two-thirds of at least 8 non-missing weekly scheduled platelet measurements during the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy. Secondary endpoints included time to platelet response (platelet count ≥50 x 109/L or between 30x109/L and <50x109/L and at least doubled from baseline in absence of rescue therapy), number of weeks maintaining a specific platelet response (i.e., doubled or within range), rescue therapy use, physical fatigue score, and bleeding score.

About Wayrilz

Wayrilz (rilzabrutinib) is the first BTK inhibitor for ITP that helps address the root cause of disease through multi-immune modulation. This innovative therapy is approved in the US for adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Additionally, Wayrilz is approved in the United Arab Emirates for adult patients with persistent or chronic ITP who have had an insufficient response or intolerance to a previous treatment. BTK, expressed in B cells, macrophages, and other innate immune cells, plays a critical role in multiple immune-mediated disease processes and inflammatory pathways. With the application of Sanofi’s TAILORED COVALENCY® technology, Wayrilz can selectively inhibit the BTK target.

Wayrilz is being studied across a variety of rare diseases, including wAIHA, IgG4-RD, and SCD. These additional indications are currently under investigation and have not been approved by regulatory authorities.

Wayrilz (rilzabrutinib) Consumer Important Safety Information

What is Wayrilz?

Wayrilz is a prescription medicine that is used to treat adults with persistent or chronic immune thrombocytopenia (ITP) who received a prior treatment that did not work well enough.

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

IMPORTANT SAFETY INFORMATION

What should I tell my healthcare provider before taking Wayrilz?

Tell your healthcare provider about all of your medical conditions, including if you:

have liver problems

have kidney problems

are pregnant or plan to become pregnant. Wayrilz may harm your unborn baby. If you are able to have a baby, your healthcare provider will do a pregnancy test before starting treatment with Wayrilz. Females who are able to become pregnant should use an effective birth control during treatment with Wayrilz and for 1 week after the last dose.

are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with Wayrilz and for at least 1 week after the last dose.

FDA Approves Wayrilz (rilzabrutinib) for Immune Thrombocytopenia

FDA Approves Wayrilz (rilzabrutinib) for Immune Thrombocytopenia

FDA Approves Wayrilz (rilzabrutinib) for Immune Thrombocytopenia

FDA Approves Dawnzera (donidalorsen) as the First and Only RNA-targeted Prophylactic Treatment for Hereditary Angioedema

Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced the U.S. Food and Drug Administration (FDA) approval of Dawnzera (donidalorsen) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. Dawnzera is the first and only RNA-targeted medicine approved for HAE, designed to target plasma prekallikrein (PKK), a key protein that activates inflammatory mediators associated with acute attacks of HAE. Dawnzera 80mg is self-administered via subcutaneous autoinjector once every four (Q4W) or eight weeks (Q8W).

HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. HAE is estimated to affect approximately 7,000 people in the U.S.

“Dawnzera represents a significant advance for people living with HAE who need improved treatment options. With strong and durable efficacy, convenient administration and the longest dosing option available, we believe Dawnzera will be the prophylactic treatment of choice for many people living with HAE. Importantly, the recently published switch data empowers patients and physicians with a roadmap for switching to Dawnzera from other prophylactic therapies,” said Brett P. Monia, Ph.D., chief executive officer, Ionis. “At Ionis, we are dedicated to turning groundbreaking science into life-changing medicines. With the early success of our first independent launch of TRYNGOLZA® for familial chylomicronemia syndrome (FCS), and now with Dawnzera, our second independent medicine approved in less than nine months, we are proudly delivering on that vision. To the patients, families, advocacy partners and investigators who helped make this moment a reality, we express our deepest gratitude.”

The approval of Dawnzera was based on positive results from the Phase 3 global, multicenter, randomized, double-blind, placebo-controlled OASIS-HAE study in patients with HAE. The study met its primary endpoint, with Dawnzera Q4W significantly reducing monthly HAE attack rate by 81% compared to placebo over 24 weeks. Mean attack rate reduction increased to 87% when measured from the second dose, a key secondary endpoint. Additionally, Dawnzera Q4W reduced moderate-to-severe HAE attacks by ~90% over 24 weeks when measured from the second dose.

These results are bolstered by the ongoing OASISplus open-label extension (OLE) study, in which Dawnzera Q8W had a similar effect as Q4W over time. Dawnzera demonstrated 94% total mean attack rate reduction from baseline across both dosing groups after one year in the OLE.

The OASISplus study also includes a switch cohort evaluating Dawnzera Q4W in patients previously treated with lanadelumab, C1-esterase inhibitor or berotralstat for at least 12 weeks. Switching to Dawnzera reduced mean HAE attack rate by 62% from prior prophylactic treatment over 16 weeks, with no mean increase in breakthrough attacks observed during the switch. A total of 84% of patients surveyed preferred Dawnzera over their prior prophylactic treatment, citing better disease control, less time to administer and less injection site pain or reactions.

Across clinical studies, Dawnzera demonstrated a favorable safety and tolerability profile. The most common adverse reactions (incidence ≥ 5%) were injection site reactions, upper respiratory tract infection, urinary tract infection and abdominal discomfort.

“As the first FDA-approved RNA-targeted therapy for HAE, Dawnzera represents a welcome advance in therapeutic options for preventing attacks. Today’s approval gives people living with HAE and their physicians another important choice for aligning treatment with individual needs,” said Anthony J. Castaldo, CEO & chairman of the board, U.S. Hereditary Angioedema Association (HAEA) and Hereditary Angioedema International (HAEi).

"People living with HAE manage this condition for all their lives, and many continue to face unpredictable, painful and dangerous breakthrough attacks even with current treatments. Durable efficacy is essential in maintaining long-term disease control,” said Marc Riedl, M.D., M.S., clinical director, U.S. HAEA Angioedema Center; University of California, San Diego; OASIS-HAE and OASISplus trial investigator. "Dawnzera is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks, continued improvement over time and reduced burden of treatment.”

Dawnzera will be available in the U.S. in the coming days.

Ionis is committed to helping people access the medicines they are prescribed and will offer a suite of services designed to meet the unique needs of the HAE community through Ionis Every Step™. As part of Ionis Every Step, patients and healthcare providers will have access to a wide range of support and resources including dedicated support from a Patient Education Manager, assistance with the insurance approval process, information on affordability programs, access to the Dawnzera Direct digital companion and other ongoing services and resources to help patients stay on track. Visit Dawnzera.com for more information.

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

FDA Approves Dawnzera (donidalorsen) as the First and Only RNA-targeted Prophylactic Treatment for Hereditary Angioedema

FDA Approves Inlexzo (gemcitabine intravesical system) for the Treatment of Non-Muscle Invasive Bladder Cancer

In continuation of my update on gemcitabine 

Johnson & Johnson (NYSE:JNJ) announced  the U.S. Food and Drug Administration (FDA) approval of  Inlexzo (gemcitabine intravesical system), a new, potentially practice-changing approach for treating patients with certain types of bladder cancer, addressing the need for additional options following unsuccessful BCG therapy and for patients refusing or ineligible for bladder removal surgery (radical cystectomy). Inlexzo, previously referred to as TAR-200, is indicated for the treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.1

Inlexzo is designed for patients seeking bladder preservation and is the first and only intravesical drug releasing system (iDRS) to provide extended local delivery of a cancer medication into the bladder. Inlexzo remains in the bladder for three weeks per treatment cycle for up to 14 cycles.1 A healthcare professional places Inlexzo into the bladder using a co-packaged urinary catheter and stylet to insert it into the bladder. Inlexzo is placed in an outpatient setting in a few minutes, without the need for general anesthesia or further monitoring immediately post-insertion within the healthcare provider’s office.1

“When we acquired this novel therapy in 2019, our ambition was to give patients with bladder cancer a renewed sense of hope and belief,” said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine, Johnson & Johnson. “In an area that has seen little progress for more than 40 years, Inlexzo delivers a first-of-its-kind breakthrough innovation with a bright future ahead.”

The approval is supported by data from the SunRISe-1 ( NCT04640623) single arm, open-label Phase 2b clinical study.1 Results show 82 percent of patients with BCG-unresponsive NMIBC treated with Inlexzo achieved a complete response (CR), meaning no signs of cancer were found after treatment (95 percent confidence interval [CI], 72, 90).1 This high response rate demonstrated strong durability, and 51 percent of these patients maintained a complete response for at least one year.1

In the SunRISe-1 clinical trial supporting this approval, the most common adverse reactions (≥15 percent) including laboratory abnormalities, were urinary frequency, urinary tract infection, dysuria, micturition urgency, decreased hemoglobin, increased lipase, urinary tract pain, decreased lymphocytes, hematuria, increased creatinine, increased potassium, increased aspartate aminotransferase (AST), decreased sodium, bladder irritation, and increased alanine transaminase (ALT).1

“I see many patients that ultimately become BCG-unresponsive and often face life-altering bladder removal. These patients now may be ideal candidates for newly approved Inlexzo,” said Sia Daneshmand, M.D., TAR-200 SunRISe-1 principal investigator, and Professor of Urology, Director of Urologic Oncology at the Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California.* “In my experience, Inlexzo is well-tolerated and delivers clinically meaningful results. This will change the way we treat appropriate patients that haven’t responded to traditional therapy.”

“We are proud of the science that has brought us to this historic moment,” said John Reed, M.D., Ph.D., Executive Vice President, R&D, Innovative Medicine, Johnson & Johnson. “Inlexzo is a novel therapy with powerful efficacy and demonstrated safety profile. As the only major healthcare company that hosts both pharmaceuticals and medical devices, we leveraged the speed and scale of Johnson & Johnson to accelerate innovation and deliver this important therapy to patients.”

“At BCAN, our mission has always been to advocate for better todays and more tomorrows for everyone impacted by bladder cancer. This approval represents the kind of progress that brings new options to a community that urgently needs them,” said Meri-Margaret Deoudes, CEO, Bladder Cancer Advocacy Network (BCAN).** “Patients with bladder cancer need guidance and collaboration with providers to navigate bladder-sparing treatment options, including newly approved treatments like Inlexzo, so they can move forward feeling well-informed and confident.”

Leading to today’s approval, the FDA granted Inlexzo Breakthrough Therapy Designation (BTD), Real-Time Oncology Review (RTOR), and Priority Review.

Johnson & Johnson is committed to helping patients access our treatments. Once a patient and their doctor have decided that Inlexzo is right for the patient, J&J withMe provides a simple, comprehensive patient support program offering cost support, a dedicated Care Navigator and educational resources, at no cost to the patient.

About SunRISe-1, Cohort 2SunRISe-1 ( NCT04640623), Cohort 2, was a single arm, open-label Phase 2b clinical study that evaluated the safety and efficacy of Inlexzo monotherapy for BCG-unresponsive NMIBC patients with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for, or elected not to undergo, radical cystectomy. The primary endpoint for Cohort 2 was complete response (CR) rate at any time point, and secondary endpoints include duration of response (DOR).

About Non-Muscle Invasive Bladder Cancer (NMIBC) and the Current Standard of Care Non-muscle invasive bladder cancer (NMIBC) is a type of non-invasive bladder cancer that can be classified as low, intermediate, or high risk depending on the presence of characteristics including tumor size, presence of multiple tumors, and carcinoma in situ (CIS).2 NMIBC with CIS makes up approximately 10 percent of patients with NMIBC.3 The current standard of care for NMIBC is Bacillus Calmette-Guérin (BCG), which is a weakened form of the bacteria found in tuberculosis treatment. Though effective, some patients become unresponsive to it and may experience challenges.4,5 Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy; it is a life-altering surgery with a high degree of morbidity and adverse impact on life, and has a post-surgery mortality rate of three to eight percent.6,7 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.

About Inlexzo

Inlexzo is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. Inlexzo is an intravesical system enabling extended release of gemcitabine into the bladder. It is placed in a few minutes without general anesthesia or further monitoring immediately post-insertion within the healthcare provider’s office.

The safety and efficacy of Inlexzo is being evaluated in clinical trials in patients with MIBC in SunRISe-4, and NMIBC in SunRISe-1, SunRISe-3, and SunRISe-

https://en.wikipedia.org/wiki/Gemcitabine#:~:text=More%20than%2010%25%20of%20users,back%20pain%2C%20and%20muscle%20pain.

FDA Approves Inlexzo (gemcitabine intravesical system) for the Treatment of Non-Muscle Invasive Bladder Cancer