FDA Approves Pivya (pivmecillinam) for the Treatment of Uncomplicated Urinary Tract Infections

Today, the U.S. Food and Drug Administration approved Pivya (pivmecillinam) tablets for the treatment of female adults with uncomplicated urinary tract infections (UTIs) caused by susceptible isolates of Escherichia coli, Proteus mirabilis and Staphylococcus saprophyticus.

“Uncomplicated UTIs are a very common condition impacting women and one of the most frequent reasons for antibiotic use,” said Peter Kim, M.D., M.S., director of the Division of Anti-Infectives in the FDA’s Center for Drug Evaluation and Research. “The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective, and Pivya will provide an additional treatment option for uncomplicated UTIs.”

Uncomplicated UTIs are bacterial infections of the bladder in females with no structural abnormalities of their urinary tract. Approximately one-half of all women experience at least one UTI in their lifetime.

Pivya’s efficacy in treating females 18 years of age or older with uncomplicated UTIs was assessed in three controlled clinical trials comparing different Pivya dosing regimens to placebo, to another oral antibacterial drug and to ibuprofen (an anti-inflammatory drug). The primary measure of efficacy for the three trials was the composite response rate, which included clinical cure (resolution of the symptoms of the uncomplicated UTI that were present in patients at trial entry and no new symptoms) and microbiological response (demonstration that the bacteria cultured from patients’ urine at trial entry was reduced). The composite response rate was assessed approximately 8 to 14 days after patients were enrolled into the studies. In the clinical trial comparing Pivya to placebo, 62% of the 137 subjects who received Pivya achieved the composite response compared to 10% of the 134 who received placebo. In the clinical trial comparing Pivya to another oral antibacterial drug, 72% of the 127 subjects who received Pivya achieved composite response compared to 76% of the 132 who received the comparator drug. In the clinical trial comparing Pivya to ibuprofen, 66% of the 105 subjects who received Pivya achieved composite response compared to 22% of the 119 who received ibuprofen.

The most common side effects of Pivya included nausea and diarrhea.

Patients should not use Pivya if they have a known history of severe hypersensitivity to Pivya or other beta-lactam antibacterial drugs. Patients should also not use Pivya if they have primary or secondary carnitine deficiency resulting from inherited disorders of mitochondrial fatty acid oxidation and carnitine metabolism, or if they are suffering from porphyria.

Pivya comes with certain warnings and precautions such as hypersensitivity reactions, severe cutaneous adverse reactions, carnitine depletion, Clostridioides difficile-associated diarrhea and interference with a newborn screening test for isovaleric acidemia, a rare metabolic disorder.

Pivya was granted Priority Review and Qualified Infectious Disease Product designations for this indication.

The FDA granted the approval of Pivya to UTILITY therapeutics Ltd.

FDA Approves Pivya (pivmecillinam) for the Treatment of Uncomplicated Urinary Tract Infections

FDA Grants Accelerated Approval for Rezdiffra (resmetirom) for the Treatment of Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH)

Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH),  announced the U.S. Food and Drug Administration (FDA)  accelerated approval for Rezdiffra (resmetirom) in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.

Bill Sibold, Chief Executive Officer of Madrigal, stated, “NASH with moderate to advanced liver fibrosis is a serious and progressive liver disease that, until now, has not had an FDA-approved therapy. The accelerated approval of Rezdiffra is a culmination of more than 15 years of research from our founder Dr. Becky Taub and a small R&D team that took on one of the biggest challenges in drug development. This is a historic moment for the NASH field and represents the best of what our industry is capable of. We’re excited to deliver Rezdiffra to patients in need.”

Becky Taub, M.D., the Founder, Chief Medical Officer and President of Research & Development of Madrigal, stated, “Madrigal would like to thank the many patients who made the accelerated approval of Rezdiffra possible by participating in our clinical studies. We believe Rezdiffra will change the treatment paradigm for NASH with moderate to advanced liver fibrosis, giving physicians a liver-directed therapy to help improve fibrosis and resolve NASH before their patients progress to cirrhosis.”

Wayne Eskridge, Co-Founder and Chief Executive Officer of the Fatty Liver Foundation, stated, “This is a day of celebration for patients with NASH who have been waiting many years for the first approved therapy. I believe this approval milestone will bring new energy and momentum to the NASH community, accelerating our efforts to improve disease education, build care pathways, and expand investment in NASH research.”

Rezdiffra is a once-daily, oral THR-β agonist designed to target key underlying causes of NASH. The accelerated approval of Rezdiffra was based on results from the Phase 3 MAESTRO-NASH trial, which was recently published in the New England Journal of Medicine. MAESTRO-NASH is an ongoing pivotal, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 1,759 patients with biopsy-confirmed NASH. Following 52 weeks of treatment, both 100 mg and 80 mg doses of Rezdiffra demonstrated statistically significant improvement compared to placebo on two primary endpoints: NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points) with no worsening of fibrosis, and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. Fibrosis improvement and NASH resolution were consistent regardless of age, gender, type 2 diabetes status, or fibrosis stage.

The Rezdiffra prescribing information does not include a liver biopsy requirement for diagnosis. The recommended dosage of Rezdiffra is based on actual body weight. For patients weighing <100 kg (220 lbs.), the recommended dosage is 80 mg orally once daily. For patients weighing ≥100 kg (220 lbs.), the recommended dosage is 100 mg orally once daily.

Stephen Harrison, M.D., Chairman for both Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and lead Principal Investigator of the MAESTRO studies, commented, “The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition. Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis.”

Dr. Harrison continued, “Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality.”

MAESTRO-NASH remains ongoing as an outcomes study designed to generate confirmatory data that, if positive, will help verify clinical benefit and may support full approval. A second ongoing outcomes trial is evaluating progression to liver decompensation events in patients with well-compensated NASH cirrhosis treated with Rezdiffra versus placebo.

Rezdiffra should not be used in patients with decompensated cirrhosis. The most common adverse reactions reported in patients treated with Rezdiffra included diarrhea, nausea, pruritis, abdominal pain, vomiting, constipation, and dizziness. Diarrhea and nausea typically began early in treatment initiation and were mild to moderate in severity. A separate, noninvasive Phase 3 trial, MAESTRO-NAFLD-1, evaluated the safety and tolerability of Rezdiffra and contributed to the safety database supporting regulatory benefit-risk assessment.

Rezdiffra is expected to be available to patients in the U.S. in April and will be distributed through a limited specialty pharmacy network. Madrigal is committed to helping appropriate patients who may benefit from Rezdiffra access the medication through the Madrigal Patient Support program. This program is designed to help patients navigate insurance and affordability challenges and provide co-pay support for eligible patients. Madrigal has also established a patient assistance program (PAP) to help patients with no insurance access Rezdiffra.

Phase 3 MAESTRO-NASH Trial Results

MAESTRO-NASH is an ongoing Phase 3 trial that enrolled 1759 patients with biopsy-confirmed NASH. Patients were randomly assigned in a 1:1:1 ratio to receive once-daily Rezdiffra at a dose of 80 mg or 100 mg or placebo. The two primary endpoints at week 52 were NASH resolution with no worsening of fibrosis and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. The key secondary endpoint was the percent change from baseline in LDL cholesterol at week 24.

Rezdiffra achieved both primary endpoints and the key secondary endpoint of the MAESTRO-NASH trial. Additionally, Rezdiffra improved liver enzymes, fibrosis biomarkers and imaging tests as compared with placebo. The primary results of the trial were published in the New England Journal of Medicine in February 2024.

Patients enrolled in the MAESTRO-NASH trial continue on therapy after the initial 52-week treatment period for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy and hepatic decompensation events, as well as all-cause mortality. The 54-month outcomes portion of the trial is designed to generate confirmatory data that, if positive, will help verify Rezdiffra’s clinical benefit and may support full approval.

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

FDA Grants Accelerated Approval for Rezdiffra (resmetirom) for the Treatment of Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH)

FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

Takeda announced the U.S. Food and Drug Administration (FDA) has approval of  Fruzaqla™ (fruquintinib), an oral targeted therapy for adults with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. Fruzaqla is the first and only selective inhibitor of all three VEGF receptor kinases approved in the U.S. for previously treated mCRC regardless of biomarker status.1,2 This approval was received under Priority Review more than 20 days ahead of the scheduled PDUFA date of November 30, 2023.

"There is a pressing need for new treatments for individuals with metastatic colorectal cancer, who have had limited options and continue to face poor outcomes. Fruzaqla is the first novel chemotherapy-free treatment option approved for patients in the U.S. regardless of biomarker status in more than a decade,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. “For far too long, healthcare providers and patients have had limited options when selecting a therapy for metastatic colorectal cancer. Fruzaqla has the potential to offer a significant survival benefit to patients without negatively impacting their quality of life.”

The approval of Fruzaqla is based on data from two large Phase 3 trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, along with the FRESCO trial conducted in China, data from which were published in JAMA. The trials investigated Fruzaqla plus best supportive care versus placebo plus best supportive care in patients with previously treated mCRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with Fruzaqla. Safety profiles were consistent across trials.

“Patients with metastatic disease are often fragile and fatigued – due to both their condition as well as the therapies they have been exposed to. An oral, chemotherapy-free option that offers a survival benefit despite treatment with prior therapies is a critical need for treating metastatic colorectal cancer,” said Cathy Eng, M.D., FACP, at Vanderbilt University Medical Center. “Colorectal cancer is a highly heterogeneous disease, making it difficult to bring advancements to patients whose cancer has metastasized. I look forward to being able to offer a new solution to appropriate patients.”

In the United States, approximately 153,000 new cases of CRC will be diagnosed in 2023, representing 7.8% of all new cancer cases.3,4 Approximately 70% of patients with CRC will experience metastatic disease, whether at diagnosis or after treatment. Metastases are the main cause of CRC-related mortality.

“We have witnessed firsthand the physical and emotional toll metastatic colorectal cancer has on patients, their families and their care teams,” said Michael Sapienza, Chief Executive Officer, at Colorectal Cancer Alliance. “We are encouraged to see the continued progress in providing new options to patients.”

Ref ; https://en.wikipedia.org/wiki/Fruquintinib

FDA Approves Fruzaqla (fruquintinib) for Previously Treated Metastatic Colorectal Cancer

FDA Approves Aurlumyn (iloprost) as the First Medication to Treat Severe Frostbite

The U.S. Food and Drug Administration approved Aurlumyn (iloprost) injection to treat severe frostbite in adults to reduce the risk of finger or toe amputation.

"This approval provides patients with the first-ever treatment option for severe frostbite,” said Norman Stockbridge, M.D., Ph.D., director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research. “Having this new option provides physicians with a tool that will help prevent the lifechanging amputation of one’s frostbitten fingers or toes."

Frostbite can occur in several stages, ranging from mild frostbite that does not require medical intervention and does not cause permanent skin damage, to severe frostbite when both the skin and underlying tissue are frozen and blood flow is stopped, sometimes requiring amputation. Iloprost, the active ingredient in Aurlumyn, is a vasodilator (a drug that opens blood vessels) and prevents blood from clotting.

Iloprost’s efficacy in treating severe frostbite was primarily established in an open-label, controlled trial that randomized 47 adults with severe frostbite, who all received aspirin by vein and standard of care, into one of three treatment groups. One of these groups (Group 1) received iloprost by vein (intravenously) for 6 hours daily for up to 8 days. The two other groups received other medications that are unapproved for frostbite, given with iloprost (Group 2) or without iloprost (Group 3). The primary measure of efficacy was a bone scan obtained 7 days after initial frostbite that was used to predict the need for amputation of at least one finger or toe.

On day 7, the bone scan finding predictive of needing amputation was observed in 0% (0 of 16) patients receiving iloprost alone (Group 1) compared to 19% (3 of 16) patients in Group 2 and 60% (9 of 15) patients in Group 3. The presence of the bone scan abnormality was significantly lower in the two groups receiving iloprost. Most patients had follow-up information on whether they subsequently underwent at least one finger or toe amputation. The need for amputation was consistent with the bone scan findings.

The most common side effects of Aurlumyn include headache, flushing, heart palpitations, fast heart rate, nausea, vomiting, dizziness, and hypotension (blood pressure that is too low). Aurlumyn also has a warning and precaution noting that it may cause symptomatic hypotension.

Aurlumyn received Priority Review and Orphan Drug designations for this indication.

Iloprost was originally approved in 2004 for the treatment of pulmonary arterial hypertension.  The FDA granted the approval of Aurlumyn to Eicos Sciences Inc.

Ref; https://en.wikipedia.org/wiki/Iloprost.

FDA Approves Aurlumyn (iloprost) as the First Medication to Treat Severe Frostbite

FDA approves tepotinib for metastatic non-small cell lung cancer | FDA

FDA approves tepotinib for metastatic non-small cell lung cancer

On February 15, 2024, the Food and Drug Administration granted traditional approval to tepotinib (Tepmetko, EMD Serono, Inc.) for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

Tepotinib

Full prescribing information for Tepmetko will be posted here.

Tepotinib was previously granted accelerated approval for this indication on February 3, 2021, based on initial overall response rate (ORR) and duration of response (DOR) in the VISION trial (NCT02864992), a multicenter, non-randomized, open-label, multicohort study. The conversion to traditional approval was based on an additional 161 patients and an added 28 months of follow-up time to assess DOR. 

Efficacy was demonstrated in a total of 313 patients with metastatic NSCLC harboring MET exon skipping alterations. Patients received tepotinib 450 mg once daily until disease progression or unacceptable toxicity.

The primary efficacy measures were ORR and DOR, determined by a Blinded Independent Review Committee. Among 164 treatment-naïve patients, ORR was 57% (95% CI: 49, 65), with 40% of responders having a DOR ≥12 months. Among 149 previously treated patients, ORR was 45% (95% CI: 37, 53), with 36% of responders having a DOR ≥12 months.

The most common adverse reactions (≥20%) were edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.

The recommended tepotinib dose is 450 mg orally once daily with food.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

FDA approves tepotinib for metastatic non-small cell lung cancer | FDA

Ipsen’s Onivyde Regimen, a Potential New Standard-of-Care First-Line Therapy in Metastatic Pancreatic Adenocarcinoma, Approved by FDA

Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application for Onivyde (irinotecan liposome injection) plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX) as a first-line treatment in adults living with metastatic pancreatic adenocarcinoma (mPDAC). This is the second approval for an Onivyde regimen in mPDAC, following the FDA’s approval in 2015 of Onivyde plus fluorouracil and leucovorin following disease progression with gemcitabine-based therapy.

“The results from the Phase III NAPOLI 3 trial represent the first positive data for an investigational regimen in first-line metastatic pancreatic adenocarcinoma versus the currently approved nab-paclitaxel and gemcitabine regimen,” said Christelle Huguet, EVP and Head of Research and Development, Ipsen. “With today’s approval, this Onivyde (NALIRIFOX) regimen can now offer a potential new standard-of-care treatment option with proven survival benefits for people living with metastatic pancreatic adenocarcinoma in the U.S.”

Pancreatic adenocarcinoma (PDAC) is the most common type of cancer that forms in the pancreas, with more than 60,000 people diagnosed in the U.S. each year and nearly 500,000 people globally.3,4 Since there are no specific symptoms in the early stages, PDAC is often detected late and after the disease has spread to other parts of the body (metastatic or stage IV).5 Characterized as a complex cancer due to rapid tumor progression, limited genetic targets and multiple resistance mechanisms,6 mPDAC has a poor prognosis with fewer than 20% of people surviving longer than one year.4,5 Overall, pancreatic cancer has the lowest five-year survival rate of all cancer types globally and in the U.S.4,5

“Metastatic pancreatic adenocarcinoma is a difficult disease to manage with very few available treatment options. Given the reality of this aggressive form of cancer and the complexity of the disease, every advance in the treatment landscape represents a meaningful improvement in patient outcomes.” said Dr. Zev Wainberg, Professor of Medicine and Co-Director of the UCLA GI Oncology Program. “The approval of this Onivyde regimen is an important milestone for people living with mPDAC, their families and healthcare providers, with the NAPOLI 3 trial having demonstrated survival benefits versus a current standard of care treatment option.”

“We are pleased that the U.S. Food and Drug Administration has issued this new approval of the NALIRIFOX regimen. With each new approved treatment, there is more hope for those who will be diagnosed in the future and people currently living with pancreatic cancer may have more time with their loved ones,” said Julie Fleshman, JD, MBA, President and CEO of Pancreatic Cancer Action Network (PanCAN), a patient advocacy organization committed to providing evidence-based information and resources to patients and caregivers, along with advancing research to improve patient outcomes. “We are thankful to the patients who participated in this clinical trial as they play a crucial role in advancing treatments for pancreatic cancer.”

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

Ipsen’s Onivyde Regimen, a Potential New Standard-of-Care First-Line Therapy in Metastatic Pancreatic Adenocarcinoma, Approved by FDA

Zevra Therapeutics Announces Resubmission of Arimoclomol New Drug Application to the U.S. Food and Drug Administration

Zevra Therapeutics, Inc. (NasdaqGS: ZVRA) a rare disease therapeutics company, today announced it resubmitted its New Drug Application (NDA) for arimoclomol, an investigational therapeutic candidate for the treatment of Niemann-Pick disease type C (NPC) to the U.S. Food and Drug Administration (FDA) on December 22, 2023. Based on standard NDA resubmission review timelines, an acknowledgment letter from the FDA that the resubmission is complete and setting the PDUFA date is expected within 30 days. Zevra expects the NDA to be classified as a Class II submission which would be subject to a review period by the FDA within six months from the date of submission.

“The Zevra team has worked diligently to deliver a high quality and thorough resubmission of the NDA for arimoclomol following multiple interactions with the FDA and after incorporating direction from the agency,” said Neil McFarlane, President and Chief Executive Officer of Zevra. “We continue to accelerate our launch preparations in anticipation of FDA approval, and believe we are one step closer to getting arimoclomol into the hands of patients who are seeking a treatment.”

“Zevra has engaged with the advocacy community, elevating the patient voice throughout arimoclomol’s development process,” said Daniel Gallo, Ph.D., Zevra’s Senior Vice President of Medical Affairs and Advocacy. “The advocacy community’s input has been instrumental in building awareness of the need for approved treatments that address the unmet needs of individuals and their caregivers living with this debilitating condition.”

Zevra believes it has addressed the issues previously raised by the FDA in the complete response letter by providing additional evidence to support the use of the Niemann-Pick type C Clinical Severity Scale (NPCCSS) and, conducting additional studies used to support the potential mechanism of action. Additionally, new data included in the resubmission comes from multiple non-clinical studies, natural history comparisons, real-world data generated from the ongoing early access programs in the United States and the European Union, as well as data from the four-year open-label extension of the Phase 2/3 clinical trial (NCT02612129). Results from this open-label trial suggest that arimoclomol reduces the long-term progression of NPC.

Arimoclomol has been evaluated in a total of 21 studies across a range of Phase 1, 2 or 3 clinical trials evaluating its safety and efficacy across more than 600 subjects in NPC, other disease or healthy subjects. The primary efficacy trial evaluating arimoclomol for the treatment of NPC was a Phase 2/3 double-blind, placebo-controlled trial (CT-ORZY-NPC-002) of arimoclomol in 50 patients with NPC.

Read More ...

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

Zevra Therapeutics Announces Resubmission of Arimoclomol New Drug Application to the U.S. Food and Drug Administration

Zealand Pharma Submits New Drug Application to the US FDA for Glepaglutide in Short Bowel Syndrome

Zealand Pharma A/S  announced the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for glepaglutide, a long-acting GLP-2 analog, for the treatment of adult patients with short bowel syndrome (SBS) dependent on parenteral support.

“Short bowel syndrome with intestinal failure is a complex, chronic and severe condition in which individuals are dependent on receiving fluids and nutrition parenterally. While life-sustaining, parenteral support poses significant restrictions on daily life and carries a risk of serious and life-threatening complications. More effective and convenient treatments to further reduce parenteral support are needed, with the ultimate goal of discontinuing parenteral support and achieving enteral autonomy,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “We believe glepaglutide, once approved, can reduce both the burden of parenteral support and of daily dosing of existing GLP-2 treatment for people living with SBS and intestinal failure, and we are pleased to submit this treatment for regulatory review and potential approval in the US.”

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

Zealand Pharma Submits New Drug Application to the US FDA for Glepaglutide in Short Bowel Syndrome

FDA Grants Soligenix Fast Track Designation for Dusquetide in the Treatment of Oral Lesions of Behçet's Disease

Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that its SGX945 (dusquetide) development program for the treatment of oral lesions of Behçet's Disease has received "Fast Track" designation from the U.S. Food and Drug Administration (FDA).

Fast track is a designation that the FDA reserves for a drug intended to treat a serious or life-threatening condition and one that demonstrates the potential to address an unmet medical need for the condition. Fast track designation is intended to facilitate the development and expedite the review of new drugs and biologics. For instance, should events warrant, Soligenix will be eligible to submit a new drug application (NDA) for SGX945 on a rolling basis, permitting the FDA to review sections of the NDA prior to receiving the complete submission. Additionally, NDAs for fast track development programs ordinarily will be eligible for priority review, which imparts an abbreviated review time of approximately six months.

"We are very pleased to have SGX945 in Behçet's Disease granted fast track designation from the FDA," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "As demonstrated by the granting of the designation, our previous studies with dusquetide in oral mucositis have clearly validated the biologic activity in aphthous ulcers induced by chemotherapy and radiation. Behçet's disease is an unmet medical need in which the underlying vasculitis leads to ulceration of the mucous membranes and skin, with up to 18,000 people in the U.S. and as many as one million people worldwide affected by this incurable disease. Given our promising results with aphthous ulcers in oral mucositis, we are hopeful dusquetide will have a role to play in helping underserved patients suffering from this difficult to treat and chronic disease and look forward to initiating the Phase 2 clinical study in 2024."

About Dusquetide

Dusquetide (the active ingredient in SGX945 (Behçet's disease) and SGX942 (oral mucositis)) is an innate defense regulator (IDR), a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body's reaction to both injury and infection towards an anti-inflammatory, anti-infective, and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host's innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma, and chemo- and/or radiation therapy. Preclinical efficacy and safety have been demonstrated in numerous animal disease models including mucositis, colitis, macrophage activation syndrome (MAS) as well as bacterial infections. In addition, potential anti-tumor activity has been demonstrated in multiple in vitro and in vivo xenograft studies.

Dusquetide has demonstrated safety and tolerability in a Phase 1 clinical study in 84 healthy human volunteers. In Phase 2 and 3 clinical studies with SGX942 in over 350 subjects with oral mucositis due to chemoradiation therapy for head and neck cancer, positive efficacy results were demonstrated, including potential long-term ancillary benefits.

Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada.

https://go.drugbank.com/drugs/DB11879

FDA Grants Soligenix Fast Track Designation for Dusquetide in the Treatment of Oral Lesions of Behçet's Disease

Defender Pharmaceuticals Receives Complete Response Letter from the U.S. Food and Drug Administration for its Intranasal Scopolamine (DPI-386) New Drug Application for the Prevention of Nausea and Vomiting Induced by Motion in Adults

Defender Pharmaceuticals, Inc. (the “Company” or “Defender”), a privately held life sciences company based in St. Louis, today announced the issuing of a Complete Response Letter (CRL) , by the U.S. Food and Drug Administration (FDA) to the Company’s New Drug Application (NDA) for intranasal scopolamine (DPI-386) for the prevention of nausea and vomiting induced by motion in adults.

“Following our review of the CRL, we plan on scheduling a formal meeting with the FDA to fully understand the issues raised in the CRL so we can develop and implement a comprehensive action plan,” said Barry I. Feinberg, M.D., President & CEO of Defender Pharmaceuticals. “We remain confident that our intranasal scopolamine is a safe and effective therapy for the prevention of motion sickness, and we will work closely with the FDA to ensure that we can bring this innovative new product to the market.”

About intranasal scopolamine (DPI-386) Development Program

Defender has worked with the United States Naval Medical Research Unit (NAMRU-D) and the National Aeronautics and Space Administration (NASA) on its intranasal scopolamine development program that is focused on specific military personnel and astronauts.

To date, more than 1,300 patients have participated in Defender clinical studies, including over 500 participants in the DPI-386-MS-33 study. Given the successful outcome of DPI-386-MS-33, Defender has submitted a New Drug Application (NDA) to the Food and Drug Administration (FDA) for DPI-386 Nasal Gel for the prevention of nausea and vomiting induced by motion in adults.

Defender is also developing intranasal formulations designed to treat a wide variety of indications. We believe these new products have the potential to help safeguard health across civilian and military populations.

About Motion-Related Discomfort
Certain motions cause discomfort in individuals while engaged in various leisure or travel-related activities. Most forms of travel, whether on land, in the air, or on the water, can trigger symptoms such as nausea and vomiting (example: flying, boating/fishing, car, bus, and train). Symptoms induced by motion can also have a detrimental impact on the ability of various military personnel and astronauts to perform assigned duties, potentially impacting readiness and negatively impacting resources. Motion-related discomfort is a common and transient response to unfamiliar or unnatural motion or contradictory spatial sensory information, resulting in decrements to performance of tasks, pallor, cold sweating, nausea and vomiting. Prolonged exposure to certain motions may induce sopite-related symptoms such as loss of drive and concentration, drowsiness, sleepiness, apathy, depression, and a feeling of impending doom.

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

Defender Pharmaceuticals Receives Complete Response Letter from the U.S. Food and Drug Administration for its Intranasal Scopolamine (DPI-386) New Drug Application for the Prevention of Nausea and Vomiting Induced by Motion in Adults

FDA Approves Miebo (perfluorohexyloctane) Ophthalmic Solution for the Treatment of the Signs and Symptoms of Dry Eye Disease

Bausch + Lomb Corporation, announced that the U.S. Food and Drug Administration (FDA) has approved Miebo™ (perfluorohexyloctane ophthalmic solution; formerly known as NOV03), for the treatment of the signs and symptoms of dry eye disease (DED). Miebo is the first and only FDA-approved treatment for DED that directly targets tear evaporation.

“Today’s FDA approval of Miebo further advances DED treatment by addressing a significant unmet need for millions of people suffering with this disease,” said Brent Saunders, chairman and CEO, Bausch + Lomb. “We are proud to bring to market the first and only prescription eye drop approved in the United States for the treatment of DED that directly targets evaporation. We expect to make Miebo commercially available in the second half of this year.”

DED affects millions of Americans and is one of the most common ocular surface disorders.1 A leading cause of DED is excessive tear evaporation, which due to an altered tear lipid layer, is often associated with the clinical signs of Meibomian gland dysfunction (MGD). An unstable tear film triggers increased ocular surface desiccation, inflammation and damage to the ocular surface.2,3 Miebo is designed to reduce tear evaporation at the ocular surface.4,5

In GOBI and MOJAVE, two phase 3 pivotal clinical trials which enrolled more than 1,200 patients (randomized 1:1 to Miebo or hypotonic saline) with a history of DED and clinical signs of MGD, Miebo consistently met its primary clinical sign and patient-reported symptom endpoint.

"In the two pivotal clinical trials, Miebo addressed the persistent and chronic nature of DED by providing sustained improvement in both the signs and symptoms of DED,” said Preeya Gupta, M.D., cornea and cataract surgeon, Triangle Eye Consultants, Raleigh, North Carolina. “Because Miebo inhibits evaporation, it may be an appropriate treatment option for patients whose tear evaporation exceeds tear supply.”

“Tear evaporation, which is a leading driver of DED, presents a significant treatment challenge. With the approval of Miebo, eye care professionals can now take a new approach to DED therapy with a first-in-class water- and preservative-free prescription treatment option that specifically addresses tear evaporation,” said Paul Karpecki, O.D., director, Cornea and External Disease, Kentucky Eye Institute, and associate professor, University of Pikeville, Kentucky College of Optometry.

Ref : Read More  

FDA Approves Lumryz (sodium oxybate) for Cataplexy or Excessive Daytime Sleepiness in Adults with Narcolepsy

In continuation of my update on Lumryz

Avadel Pharmaceuticals plc   a biopharmaceutical company announced   the U.S. Food & Drug Administration (FDA)  final approval to Lumryz, an extended-release formulation of sodium oxybate indicated to be taken once at bedtime for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy. With final approval, Lumryz becomes the first and only FDA approved once-at-bedtime oxybate for people living with narcolepsy. Lumryz was additionally granted Orphan Drug Exclusivity by the FDA.

“Today’s landmark approval and receipt of Orphan Drug Exclusivity represents a major milestone for both Avadel and people living with narcolepsy. As we have heard from key stakeholders, previously approved narcolepsy therapies have the potential to disrupt sleep by either causing insomnia or through forced awakening during the middle of the night for their crucial second dose. Lumryz can now offer people with narcolepsy the opportunity for an uninterrupted night sleep while receiving the full benefit of their prescribed treatment in one single bedtime dose that addresses their symptoms of narcolepsy,” said Greg Divis, Chief Executive Officer of Avadel. “We would like to thank the patients, caregivers, clinical trial investigators, healthcare providers, and advocates who have tirelessly partnered with us throughout the drug development process and look forward to providing the narcolepsy community access to now approved Lumryz.”

Narcolepsy is a chronic neurological condition that impairs the brain's ability to regulate the sleep-wake cycle. The condition affects approximately one in 2,000 people in the United States with the cardinal symptom of EDS. Additional symptoms can vary by person but may include disrupted nighttime sleep, a sudden loss of muscle tone usually triggered by strong emotion (cataplexy), sleep paralysis and hallucinations.

“This long-awaited therapy for people living with narcolepsy fills a critical unmet need by avoiding the burden of a second middle-of-the-night dose that immediate-release oxybate products require. The once-at-bedtime dosing regimen of Lumryz may help restore a more natural sleep-wake cycle,” said Michael J. Thorpy, M.D., an investigator from the REST-ON Phase 3 trial and Director at the Sleep-Wake Disorders Center at Montefiore Medical Center and Professor of Neurology at the Albert Einstein College of Medicine.

The FDA’s final approval of Lumryz was based on positive results from the pivotal Phase 3 REST-ON clinical study completed in March 2020. In the REST-ON Phase 3 trial, once-at-bedtime Lumryz demonstrated highly statistically significant (p<0.001) and clinically meaningful improvement compared to placebo across all three co-primary endpoints (Maintenance of Wakefulness Test, Clinical Global Impression-Improvement and mean weekly cataplexy attacks) for all three doses evaluated, 6, 7.5 and 9 grams.

With this approval, the FDA has also found Lumryz to be clinically superior to currently marketed twice-nightly oxybate products and granted Lumryz seven years of Orphan Drug Exclusivity. In particular, FDA found that Lumryz makes a major contribution to patient care over currently available, twice-nightly oxybate products by providing a once-nightly dosing regimen that avoids nocturnal arousal to take a second dose. The FDA's Orphan Drug program is designed to support the development of drugs that treat a condition affecting less than 200,000 U.S. patients. The seven-year market exclusivity for Lumryz began on the date of FDA approval, May 1, 2023.

“For people living with narcolepsy, and for all of us who advocate for this community, the approval of Lumryz is an important step forward,” said Julie Flygare, JD, President and CEO of Project Sleep. “People living with narcolepsy will finally have a new treatment option to manage EDS and cataplexy, and the fact that this new oxybate option allows for reduced dosing frequency is a game-changing advancement that shows Avadel’s commitment to understanding the patient experience. We look forward to continued collaboration with Avadel as part of a shared mission to positively impact the lives of people with narcolepsy.”

Lumryz has a boxed warning as a central nervous system depressant, and for its potential for abuse and misuse. Lumryz is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the Lumryz REMS. Most common adverse reactions (incidence > 5% and greater than placebo) reported for all doses of Lumryz combined were nausea, dizziness, enuresis, headache, and vomiting.

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

FDA Approves Lumryz (sodium oxybate) for Cataplexy or Excessive Daytime Sleepiness in Adults with Narcolepsy

FDA Approves Mydcombi (tropicamide and phenylephrine hydrochloride) Ophthalmic Spray for Inducing Mydriasis

In continuation of my update on phenylephrine hydrochloride

Phenylephrine

Tropicamide

Eyenovia, Inc, announced  the U.S. Food and Drug Administration (FDA)  approval of Mydcombi (tropicamide and phenylephrine hydrochloride ophthalmic spray) 1%/2.5% for inducing mydriasis for diagnostic procedures and in conditions where short term pupil dilation is desired. This represents the first approved fixed dose combination of tropicamide and phenylephrine in the United States and also the first product using Eyenovia’s proprietary Optejet device to be approved by any regulatory authority.

Mydcombi is designed to improve the efficiency of the estimated 106 million office-based comprehensive eye exams performed every year in the United States, as well as the estimated 4 million pharmacologic mydriasis applications for cataract surgery. The product is contraindicated and should not be used in patients with known hypersensitivity to any component of the formulation.

“The approval of Mydcombi, our first FDA approved product, represents the culmination of years of tireless effort by the entire Eyenovia team, and I would like to express my sincere gratitude to the associates and technical experts who helped advance this important program through this transformational milestone,” stated Michael Rowe, chief executive officer of Eyenovia. “We look forward to introducing Mydcombi to key offices beginning this summer while we bring our internal manufacturing capabilities on-line for 2024.”

“Perhaps more importantly, FDA approval of Mydcombi provides critical validation of the Optejet as it is the first product approved using the Optejet platform, which is core not only to our internal development programs, including MicroLine for presbyopia, but our partnered programs as well. We see opportunities to unlock significant opportunities in the future treatment of other ophthalmic conditions including glaucoma and dry eye. I am confident in our ability to maintain our current momentum.”

“I am proud of our team for this significant achievement – which represents many ‘firsts’ for eye care,” stated Dr. Sean Ianchulev, Founder and Chairman of Eyenovia’s Board of Directors. “The use of eye dropper bottles has presented challenges for dosing in ophthalmologic settings in millions of patients. We can do better now using sophisticated micro-array print delivery with physiologic dosing that is similar to the natural tear film volume.”

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

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

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FDA Grants Accelerated Approval for Qalsody (tofersen) for the Treatment of Amyotrophic Lateral Sclerosis Associated with a Mutation in the SOD1 Gene

Biogen Inc. (Nasdaq: BIIB) announced the U.S. Food and Drug Administration (FDA)   approval of  Qalsody (tofersen) 100 mg/15mL injection for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. This indication is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with Qalsody. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trial(s).1 The ongoing Phase 3 ATLAS study of tofersen in people with presymptomatic SOD1-ALS will serve as the confirmatory trial.

Neurofilaments are proteins that are released from neurons when they are damaged, making them a marker of neurodegeneration.6

“For more than a decade, Biogen has been steadfast in our commitment to pursuing treatments for ALS, and I want to thank the scientists as well as the entire ALS community who have all worked tirelessly to bring this first-of-its-kind treatment to people with SOD1-ALS,” said Christopher A. Viehbacher, President and Chief Executive Officer of Biogen. “Today also marks a pivotal moment in ALS research as we gained, for the first time, consensus that neurofilament can be used as a surrogate marker reasonably likely to predict clinical benefit in SOD1-ALS. We believe this important scientific advancement will further accelerate innovative drug development for ALS.”

Qalsody is the first approved treatment to target a genetic cause of ALS. Biogen collaborated with Ionis Pharmaceuticals on the early development of tofersen.

Warnings and precautions associated with Qalsody were serious neurologic events, including myelitis and/or radiculitis; papilledema and elevated intracranial pressure; and aseptic meningitis. If symptoms consistent with myelitis, radiculitis papilledema, elevated intracranial, or aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care. Management may require interruption or discontinuation of Qalsody. The most common adverse reactions that occurred in ≥10% of Qalsody treated participants and more than the placebo arm were pain, fatigue, arthralgia, cerebrospinal (CSF) white blood cell increased, and myalgia.

“Since SOD1 mutations were first identified as a cause of ALS 30 years ago, the familial ALS community has been searching for genetically targeted treatments. Qalsody offers families who have lost generation after generation in the prime of their life to this devastating disease a therapy targeting the underlying cause of SOD1-ALS. Today marks an important moment in ALS research as Qalsody is the first ALS treatment approved based on a biomarker,” said Jean Swidler, chair of Genetic ALS & FTD: End the Legacy. “We are excited to see what future therapies are developed now that it is understood that lowering levels of neurofilament provides important evidence that a treatment is affecting the neurodegenerative process.”

The efficacy of Qalsody was assessed in a 28-week randomized, double-blind, placebo-controlled clinical study in patients 23 to 78 years of age with weakness attributable to ALS and a SOD1 mutation confirmed by a central laboratory. One hundred eight (108) patients were randomized 2:1 to receive treatment with either Qalsody 100 mg (n=72) or placebo (n=36) for 24 weeks (3 loading doses followed by 5 maintenance doses). Concomitant riluzole and/or edaravone use was permitted for patients and at baseline 62% of patients were taking riluzone, and 8% of patients were taking edaravone.

Over 28 weeks in VALOR, participants in the primary analysis population (n=60) treated with Qalsody experienced less decline from baseline as measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) compared to placebo, though the results were not statistically significant (Qalsody-placebo adjusted mean difference [95% CI]: 1.2 [-3.2, 5.5]). In the overall intent-to-treat population (n=108), Qalsody-treated participants experienced a 55% reduction in plasma NfL compared to a 12% increase in placebo-treated participants (difference in geometric mean ratios for Qalsody to placebo: 60%; nominal p<0.0001). Additionally, levels of CSF SOD1 protein, an indirect measure of target engagement, were reduced by 35% in the Qalsody-treated group compared to 2% in the corresponding placebo group (difference in geometric mean ratios for Qalsody to placebo: 34%; nominal p<0.0001).

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

https://go.drugbank.com/drugs/DB14782

FDA Grants Accelerated Approval for Qalsody (tofersen) for the Treatment of Amyotrophic Lateral Sclerosis Associated with a Mutation in the SOD1 Gene

FDA Approves Abilify Asimtufii (aripiprazole) for the Treatment of Schizophrenia or Maintenance Monotherapy Treatment of Bipolar I Disorder in Adults

In continuation of my update on aripiprazole

Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Lundbeck Pharmaceuticals LLC (Lundbeck) announced the U.S. Food and Drug Administration (FDA)   approval of  the New Drug Application (NDA) for Abilify Asimtufii® (aripiprazole) extended-release injectable suspension for intramuscular use, a once-every-two-months injection for the treatment of schizophrenia in adults or for maintenance monotherapy treatment of bipolar I disorder in adults.

Abilify Asimtufii offers two months of sustained therapeutic concentrations with one dose. Each dose is provided in a single-chamber, prefilled syringe, and is administered by a healthcare professional to appropriate patients via intramuscular injection in the gluteal muscle. Long-acting injectables provide continuous delivery of antipsychotic medication and can maintain therapeutic plasma concentrations, which may help to maintain symptom control of schizophrenia and bipolar I disorder.

"We are pleased to offer this new treatment option for people living with schizophrenia or bipolar I disorder that may delay the time to relapse," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka Pharmaceutical Development & Commercialization, Inc. "This approval underscores Otsuka's commitment to innovate and continuously evolve to meet the needs of the communities we serve."

The efficacy of Abilify Asimtufii is based on the adequate and well-controlled studies of Abilify Maintena (aripiprazole) in the treatment of schizophrenia or maintenance treatment of bipolar I disorder in adults. The aripiprazole concentrations of Abilify Asimtufii were explored in a pharmacokinetic bridging study which was a 32-week, open-label, multiple-dose, randomized, parallel-arm, multicenter study (N=266) in patients living with schizophrenia and bipolar I disorder. The once-every-two-months, long-acting injectable formulation in 960 mg and 720 mg prefilled syringes delivers sustained plasma concentrations similar to that demonstrated in studies with aripiprazole monohydrate once-monthly, long-acting injectable, resulting in similar sustained efficacy.

"This approval is important news for patients, families, and healthcare providers. We hope that the use of Abilify Asimtufii in treatment plans will have a positive impact on those living with schizophrenia or bipolar I disorder," said Johan Luthman, executive vice president, R&D, Lundbeck. "We are grateful to the patients and researchers who made this major milestone possible."

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

FDA Approves Abilify Asimtufii (aripiprazole) for the Treatment of Schizophrenia or Maintenance Monotherapy Treatment of Bipolar I Disorder in Adults

FDA Approves Uzedy (risperidone) Extended-Release Injectable Suspension for the Treatment of Schizophrenia in Adults

In continuation of my update on Uzedy (risperidone)

Teva Pharmaceuticals,  announced  the U.S. Food and Drug Administration (FDA)  approval of  Uzedy (risperidone) extended-release injectable suspension for the treatment of schizophrenia in adults. Uzedy is the first subcutaneous, long-acting formulation of risperidone that utilizes SteadyTeq™, a copolymer technology proprietary to MedinCell that controls the steady release of risperidone. Therapeutic blood concentrations are reached within 6-24 hours of a single dose. 

“Uzedy embodies Teva’s commitment to bringing innovative advances to patients and to providing people living with schizophrenia an important new treatment option that was designed to address certain treatment challenges and may decrease the risk of relapse,” said Richard Francis, President and CEO of Teva. “The approval of Uzedy is a culmination of a multidisciplinary effort across Teva and MedinCell to bring this important treatment to market. This milestone is a testament to advancing our robust biopharmaceutical pipeline of innovative medicines that aim to support more people living with mental health disorders and neurological diseases in the coming years.”

Approximately 80% of patients with schizophrenia experience multiple relapses over the first five years of treatment,2 most commonly due to suboptimal adherence to treatment with oral antipsychotics. Each relapse carries a biological risk of loss of function, treatment refractoriness, and changes in brain morphology.3,4

Schizophrenia is a chronic, progressive and severely debilitating mental health disorder that affects how one thinks, feels and acts.5 This approval is based on data from two Phase 3 trials evaluating Uzedy in patients with schizophrenia: TV46000-CNS-30072 (the RISE Study – The Risperidone Subcutaneous Extended-Release Study) and TV46000-CNS-30078 (the SHINE Study – A Study to Test TV-46000 for Maintenance Treatment of Schizophrenia).

“The approval of the first product formulated with our technology is a pivotal moment for MedinCell and for the many patients who will benefit,” said Christophe Douat, CEO of MedinCell. “We are committed to supporting patients through innovative therapy options. It continues to be a wonderful journey with Teva, an ideal partner to harness the full potential of Uzedy. Our technology reaching commercial stage marks the start of an exciting new era for MedinCell and we are extremely proud to share this very special moment with all our employees and shareholders.”

The use of novel SteadyTeq technology in Uzedy controls the release of risperidone over time. The initiation of treatment requires no loading dose or oral supplementation. Therapeutic blood concentrations are reached within 6-24 hours of a single dose. 

“Treatments for schizophrenia are largely prescribed as daily oral medications, which can present challenges with adherence due to missed doses. Lack of adherence to treatment with oral antipsychotics is the most common cause of relapse in schizophrenia  so there’s a role for therapies that are dosed in one- or two-month dosing intervals to help prevent relapse,” said Christoph Correll, MD, professor of psychiatry at the Zucker School of Medicine, Hempstead, NY. “As a clinician, I am excited to now have a new treatment option that reduces the risk of relapse1 for this complex disease and helps address some of the barriers around receiving schizophrenia treatment.”

https://pubchem.ncbi.nlm.nih.gov/compound/Risperidone#section=2D-Structure

FDA Approves Uzedy (risperidone) Extended-Release Injectable Suspension for the Treatment of Schizophrenia in Adults