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

Chugai files for additional indication of Evrysdi for pre-symptomatic SMA and additional dosage for infants up to 2 months of age

Chugai Pharmaceutical Co., Ltd. announced that it filed regulatory application with the Ministry of Health, Labour and Welfare (MHLW) of “Evrysdi dry syrup 60 mg ” (Evrysdi), a treatment for spinal muscular atrophy, for an additional indication of pre-symptomatic SMA, and an additional dosage for infants up to the 2 months of age. The drug received orphan drug designation from the MHLW in March 2019, for SMA, and the application for additional indication is also subject to priority review.

“There is great significance in filing for additional indication for pre-symptomatic SMA, as initiation of treatment before onset of symptoms may possibly maximize treatment benefit. In addition, availability of this drug in all ages including infants from birth may enable treatment to be started promptly after diagnosis. We remain committed towards obtaining additional indication approval of Evrysdi, to provide benefit as the only approved oral treatment for SMA” said Chugai’s president and CEO, Dr. Osamu Okuda.

The application is based on results from the RAINBOWFISH study, an overseas phase II study (does not include Japan) for pre-symptomatic SMA infants. The RAINBOWFISH study included babies with two or more copies of the SMN2 gene. Generally, the lower the number, the more severe the disease.

The study met its primary endpoint with 80% of the primary efficacy population (n=5) sitting without support for at least five seconds after 1 year of Evrysdi treatment, assessed by Bayley Scales of Infant and Toddler Development, third edition (BSID-III). The primary efficacy population included babies with two SMN2 copies and a CMAP (compound muscle action potential) amplitude of =1.5 mV at baseline. CMAP amplitude measures the muscle response to a stimulus, and a low score correlates with symptom onset in SMA patients and worse functional outcomes. Patients in the primary efficacy population are expected to progress similarly to the natural history of SMA Type I without treatment, and in that case, children with Type 1 SMA would not be expected to sit. Of the 26 babies in the study, 81% could sit independently for 30 seconds, including all patients with low CMAP amplitude at baseline (<1.5 mV) and the majority were standing and walking.

Adverse events (AEs) were more reflective of the age of the babies than underlying SMA. The majority of AEs were not considered treatment-related, and there were no deaths or AEs leading to withdrawal or treatment discontinuation. The most common AEs were teething, Covid-19, pyrexia, gastroenteritis, eczema and constipation. The AEs observed in the RAINBOWFISH primary analysis are generally consistent with those AEs seen in other Evrysdi trials in SMA.

In SMA, the loss of motor neurons may begin before symptoms start so initiating treatment early is critical for better outcomes, and newborn screening plays an important role for early diagnosis. Evrysdi is expected to offer high medical value by enabling immediate start of treatment after diagnosis.

The RAINBOWFISH study [NCT03779334] is an open-label, single-arm, multicentre study, investigating the efficacy, safety, pharmacokinetics, and pharmacodynamics of Evrysdi in babies (n=26), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. Proportion of infants in the primary efficacy population who are sitting without support for at least 5 seconds at month 12 assessed by the BSID-III (Bayley Scales of Infant and Toddler Development - Third Edition) gross motor scale. Japan is not included in this study.

Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Evrysdi is designed to treat SMA by increasing and sustaining the production of the survival motor neuron (SMN) protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement. Evrysdi was approved in the US in August 2020, in Europe in March 2021, and in Japan in June 2021.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disease that causes muscule atrophy and muscle weakness due to degeneration of the motor neuron. The causative gene for SMA is the survival motor neuron (SMN) gene. The disease develops because of insufficient production of functional SMN protein from SMN2 genes alone, in addition to the dysfunction of the SMN1 gene.

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

Chugai files for additional indication of Evrysdi for pre-symptomatic SMA and additional dosage for infants up to 2 months of age

Tapinarof Cream Under FDA Review for Atopic Dermatitis Indication | MDedge Dermatology

Dermavant Sciences announced  the company's  submission of  supplemental New Drug Application (sNDA) to the Food and Drug Administration for tapinarof cream, 1%, for treating atopic dermatitis (AD) in adults and children 2 years of age and older.

Tapinarof cream, 1%, is an aryl hydrocarbon receptor agonist marketed under the brand name VTAMA that was approved in 2022 for treating plaque psoriasis in adults.

According to a Dermavant press release, the sNDA is based on positive data from the phase 3 ADORING 1 and ADORING 2 pivotal trials and interim results from the phase 3 ADORING 3 open-label, long-term extension 48-week trial. In ADORING 1 and ADORING 2, tapinarof cream demonstrated statistically significant improvements in the primary endpoint of Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) treatment success, defined as a vIGA-AD score of 0 (clear) or 1 (almost clear) with at least a 2-grade improvement from baseline; demonstrated treatment success over vehicle at week 8; and met all key secondary endpoints with statistical significance, according to the company.

The most common adverse reactions in patients treated with VTAMA cream include folliculitis, nasopharyngitis, contact dermatitis, headache, and pruritus.

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

Tapinarof Cream Under FDA Review for Atopic Dermatitis Indication | MDedge Dermatology

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

UCLA-led research results in FDA approval of 4-drug combination for frontline treatment of metastatic pancreatic cancer

A four-drug chemotherapy regimen of irinotecan liposome (Onivyde) in combination with oxaliplatin, leucovorin, and fluorouracil—together referred to as NALIRIFOX—has been approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of metastatic pancreatic adenocarcinoma.

                                                                            Irinotecan

                                                                      Fluorouracil

                                                                    Folinic acid

                                                                Oxaliplatin

The FDA approval was based on results of the NAPOLI 3 trial, a study led by Dr. Zev Wainberg, co-director of the UCLA Health GI Oncology Program and a researcher at the UCLA Health Jonsson Comprehensive Cancer Center.

Findings from the NAPOLI 3 trial were first presented at the 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium annual meeting and published in the Lancet in September of 2023. Wainberg, the global principal investigator for the trial, reported NALIRIFOX resulted in longer overall survival than a two-drug protocol comprised of nab-paclitaxel (Abraxane) and gemcitabine.

“The FDA approval is significant because of how difficult it is to treat metastatic pancreatic cancer,” said Wainberg, who is also a professor of medicine at the David Geffen School of Medicine at UCLA. “Metastatic pancreas cancer has long been recognized as a very difficult type of cancer to treat, but this study represents a possible new benchmark standard for current therapies and a promising avenue for ongoing research and drug development.”

The phase 3 study included 770 patients with pancreatic ductal adenocarcinoma, which makes up 95% of pancreatic cancers. Participants were from 250 sites in 25 countries and were randomly assigned to NALIRIFOX or the two-drug therapy.

Patients in the NALIRIFOX group had an overall survival of 11.1 months, compared with 9.2 months for those in the two-drug arm. Progression-free survival also increased with NALIRIFOX to 7.4 months versus 5.6 months with the two-drug regimen, which translates into a 30% reduction in the risk of disease progression or death.

The study is believed to be the first metastatic pancreatic cancer study in nearly a decade to have a positive endpoint for overall survival.

Most cases of pancreatic cancer are diagnosed at more advanced stages when the disease is more aggressive and has already started spreading to other parts of the body. There are also limited treatment options, which contributes to the high fatality rate of pancreatic cancer—Only about 13% of patients survive five or more years. In 2024 alone, the American Cancer Society estimates that around 35,000 people are anticipated to die from the disease.

The most common side effects people experienced in the trial included diarrhea, fatigue, nausea, vomiting, reduced appetite, abdominal pain, mucosal inflammation, constipation and decreased weight.

https://www.sciencedirect.com/science/article/pii/S0140673623013661?via%3Dihub

UCLA-led research results in FDA approval of 4-drug combination for frontline treatment of metastatic pancreatic cancer

New treatment for a rare and aggressive cancer improves survival rates in breakthrough clinical trial

An innovative treatment significantly increases the survival of people with malignant mesothelioma, a rare but rapidly fatal type of cancer with few effective treatment options, according to results from a clinical trial led by Queen Mary University of London. 

The phase 3 clinical trial, led by Professor Peter Szlosarek at Queen Mary and sponsored by Polaris Pharmaceuticals, has unveiled a breakthrough in the treatment of malignant pleural mesothelioma (MPM), a rare and often rapidly fatal form of cancer with limited therapeutic options.  

Mick’s journey with mesothelioma: “I have five grandchildren and two great-grandchildren now – I wouldn’t want to miss all that.” 

The ATOMIC-meso trial, a randomised placebo-controlled study of 249 patients with MPM, found that a treatment – which combines a new drug, ADI-PEG20, with traditional chemotherapy – increased the median survival of participants by 1.6 months, and quadrupled the survival at 36 months, compared to placebo-chemotherapy.  

The findings are significant, as MPM has one of the lowest 5-year survival rates of any solid cancer of around 5-10%. This innovative approach marks the first successful combination of chemotherapy with a drug that targets cancer's metabolism developed for this disease in 20 years. 

MPM is a rare, aggressive cancer that affects the lining of the lungs and is associated with exposure to asbestos. It’s usually treated with potent chemotherapy drugs, but these are seldom able to halt the progression of the disease.  

The premise behind this new drug treatment is elegant in its simplicity – starving the tumour by cutting off its food supply. All cells need nutrients to grow and multiply, including amino acids like arginine. ADI-PEG20 works by depleting arginine levels in the bloodstream. For tumour cells that can't manufacture their arginine due to a missing enzyme, this means their growth is thwarted.  

The ATOMIC-meso trial is the culmination of 20 years of research at Queen Mary’s Barts Cancer Institute that began with Professor Szlosarek’s discovery that malignant mesothelioma cells lack a protein called ASS1, which enables cells to manufacture their own arginine. He and his team have since dedicated their efforts to using this knowledge to create an effective treatment for patients with MPM. 

Professor Szlosarek said:  “It's truly wonderful to see the research into the arginine starvation of cancer cells come to fruition. This discovery is something I have been driving from its earliest stages in the lab, with a new treatment, ADI-PEG20, now improving patient lives affected by mesothelioma. I thank all the patients and families, investigators and their teams, and Polaris Pharmaceuticals for their commitment to defining a new cancer therapy.” 

Dr Tayyaba Jiwani, Science Engagement Manager at Cancer Research UK, said:  "This study shows the power of discovery research which allows us to dig deep into the biology of mesothelioma to uncover vulnerabilities that we can now target with ADI-PEG20.  

"Cancer Research UK is delighted to have funded the early stages of this research, including a preliminary clinical trial which established the safety and effectiveness of this drug." 

There are ongoing studies assessing ADI-PEG20 in patients who have sarcoma or glioblastoma multiforme (a type of brain tumour) and other cancers dependent on arginine. The success of this novel chemotherapy in MPM also suggests that the drug may be of benefit in the treatment of multiple other types of cancer.  

Mick’s journey with mesothelioma  

Mick worked in a factory boiler room in the 1970s, where he was exposed to asbestos. In 2018, he visited his doctor after he began to feel unwell and had lost three stone in weight. He became anaemic and was eventually diagnosed with mesothelioma. 

“It was a bit of a shock: I was given four months to live,” Mick explains. His doctor referred him to Professor Szlosarek, who enrolled him in the ATOMIC-meso trial. “I always believed in Peter. I said: ‘I’m in it to win it – you’re not getting rid of me.’ And here I am five years later.” 

For two years, Mick visited St Bartholomew’s Hospital every week, accompanied by his wife, Jackie, or one of his children or grandchildren. “I’d have two injections of the new treatment – one in each arm. I didn’t have any serious side effects,” Mick explains. “I met many of the other people on the trial. Over time, some of them disappeared. But I kept going.”  

Mick was awarded compensation from his former employer responsible for the asbestos exposure that ultimately led to his mesothelioma. Around 80% of mesothelioma cases are caused by workplace exposure. 

Two and a half years after Mick enrolled on the ATOMIC-meso trial, his mesothelioma returned and he received a second course of treatment, this time immunotherapy. He experienced more side effects with this therapy, including encephalitis. But his cancer remains under control, and recently he was able to celebrate his 80th birthday. Professor Szlosarek and his team plan to study why certain patients, such as Mick, benefit so greatly from ADI-PEG20, in the hope of discovering how to extend this benefit to more people.  

Mick says: “This trial has changed the lives of people with mesothelioma, allowing us to live longer. I have five grandchildren and two great-grandchildren now – I wouldn’t want to miss all that.” 

https://jamanetwork.com/journals/jamaoncology/fullarticle/2815000

New treatment for a rare and aggressive cancer improves survival rates in breakthrough clinical trial

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

Journey Medical Corporation Submits New Drug Application to FDA for DFD-29 to Treat Rosacea

Journey Medical Corporation,  announced that the Company has submitted,  a New Drug Application (“NDA”) to the FDA seeking approval for DFD-29 (Minocycline Hydrochloride Modified Release Capsules, 40 mg) for the treatment of inflammatory lesions and erythema of rosacea in adults. DFD-29 is being developed in collaboration with Dr. Reddy’s Laboratories Ltd.

“This NDA submission is a significant milestone for Journey Medical and we look forward to collaborating with the FDA during its review to bring DFD-29, a potentially differentiated, best-in-class oral rosacea treatment, one step closer to patients. Based on the data seen in our pivotal trials, DFD-29 could fundamentally improve the treatment paradigm for patients suffering from both inflammatory lesions and erythema (redness) from rosacea,” said Claude Maraoui, Co-Founder, President and Chief Executive Officer of Journey Medical.

The NDA submission is supported by positive data from Journey Medical’s two DFD-29 Phase 3 clinical trials for the treatment of rosacea. The Phase 3 clinical trials achieved all co-primary and secondary endpoints, and subjects completed the 16-week treatment with no significant safety issues. DFD-29 demonstrated statistical superiority over both the current standard-of-care treatment, Oracea® 40 mg capsules, and placebo for Investigator’s Global Assessment treatment success as well as the reduction in the total inflammatory lesion count in both studies. On a secondary endpoint related to erythema (redness) assessment, DFD-29 showed statistically significant reduction in Clinician’s Erythema Assessment (CEA) compared to placebo in both clinical trials.

Rosacea, which affects approximately 16 million people in the United States according to the National Rosacea Society, is a long-term, inflammatory skin condition that causes small, red, pus-filled bumps, redness and visible blood vessels in the face. DFD-29 has the potential to become the only oral, systemic therapy to address both inflammatory lesions and erythema (redness) from rosacea, as demonstrated in the clinical trials.

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

Journey Medical Corporation Submits New Drug Application to FDA for DFD-29 to Treat Rosacea

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

FDA Approves Augtyro (repotrectinib) for the Treatment of Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer (NSCLC)

Bristol Myers Squibb (NYSE: BMY) announced  the U.S. Food and Drug Administration (FDA) approval of  Augtyro (repotrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). Administered as an oral therapy, Augtyro is a tyrosine kinase inhibitor (TKI) targeting ROS1 oncogenic fusions.

The approval is based on the TRIDENT-1 study, an open-label, single-arm, Phase 1/2 trial that evaluated Augtyro in TKI-naïve and TKI-pretreated patients.2 In TKI-naïve patients (n=71), the primary endpoint of objective response rate (ORR), defined as the percentage of people treated within a certain period of time whose tumor size decreased (partial response) or who no longer have signs of cancer (complete response),was 79% (95% Confidence Interval [CI]: 68 to 88).1,3 The median duration of response (mDOR) was 34.1 months. Among patients pretreated with one prior ROS1 TKI and no prior chemotherapy (n=56), the ORR was 38% (95% CI: 25 to 52) and the mDOR was 14.8 months.1 Among those who had measurable central nervous system (CNS) metastases at baseline, responses in intracranial lesions were observed in 7 of 8 TKI-naïve patients (n=71) and 5 of 12 of those who were TKI-pretreated (n=56).

“New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,” said Jessica J. Lin, MD, TRIDENT-1 primary investigator and attending physician at the Center for Thoracic Cancers at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School.4,5,6,7 “Based on the data we have seen in the TRIDENT-1 trial, repotrectinib has the potential to become a new standard of care option for patients with locally advanced or metastatic ROS1 fusion-positive lung cancer.”1

Augtyro is associated with the following Warnings & Precautions: central nervous system (CNS) effects, interstitial lung disease (ILD)/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryo-fetal toxicity.1 Please see Important Safety Information below.

“While progress has been made in the treatment of NSCLC over the past decade, there is still a need to address this particularly difficult-to-treat form of the disease with innovative science and a targeted approach,” said Samit Hirawat, MD, executive vice president, chief medical officer, Global Drug Development, Bristol Myers Squibb.6,7 “As the only approved next-generation TKI for ROS1-positiveNSCLCpatients, Augtyro builds on our legacy of delivering transformational therapies for patients with thoracic cancers.”6,8,9

“ROS1-positive NSCLC patients and their families face a stressful journey because our cancer can be difficult to treat, especially when it spreads to the brain,” said Janet Freeman-Daily, co-founder and president of The ROS1ders, a patient advocacy organization.10 “Today’s approval brings a new treatment option for the ROS1-positive patient community, which gives us hope for more time with loved ones.”

Augtyro is designed to minimize interactions that can lead to certain forms of treatment resistance in ROS1-positive metastatic NSCLC patients. Itis expected to be available to patients in the U.S. in mid-December 2023. Bristol Myers Squibb thanks the patients and investigators involved in the TRIDENT-1 clinical trial program.

ref ;https://en.wikipedia.org/wiki/Repotrectinib

FDA Approves Augtyro (repotrectinib) for the Treatment of Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer (NSCLC)

Bridgebio Pharma Announces U.S. Food and Drug Administration (FDA) Acceptance of New Drug Application (NDA) for Acoramidis for the Treatment of Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s New Drug Application (NDA) for acoramidis, an investigational drug for the treatment of ATTR-CM. The application was based on positive results from ATTRibute-CM, the Company’s Phase 3 study designed to evaluate the efficacy and safety of acoramidis, an investigational, next-generation, orally-administered, highly potent, small molecule stabilizer of transthyretin (TTR). The FDA has set an action date of November 29, 2024 under the PDUFA. The FDA also notified the Company that it is not currently planning to hold an advisory committee meeting to discuss the application.

 

“The FDA’s acceptance of our NDA submission for review reinforces our belief in acoramidis and its potential to make an important contribution to the care of patients with ATTR-CM,” said Jonathan Fox, MD, PhD, President and Chief Medical Officer of BridgeBio Cardiorenal. “We look forward to the upcoming review process and the potential for approval in the United States. Similarly, with the European Marketing Authorization Application accepted and with plans to extend our submissions to other countries and regions, we are committed to making acoramidis available to patients.”

In July 2023, BridgeBio announced positive results from ATTRibute-CM, reporting a highly statistically significant result, demonstrated by a Win Ratio of 1.8 (p<0.0001) on the primary endpoint (a hierarchical analysis prioritizing in order: ACM, then frequency of CVH, then change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), then change from baseline in 6-minute walk distance (6MWD)). Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified. BridgeBio has also presented analyses from ATTRibute-CM at the European Society of Cardiology Congress 2023 and at the American Heart Association Scientific Sessions 2023.

“As part of our mission, we seek to improve the lives of patients with amyloidosis by providing support to them and their caregivers throughout their journey. There is a need for more treatment options that can help fill the significant unmet need that exists for patients today. We are excited by BridgeBio’s recent NDA acceptance from the FDA, which we hope moves us one step closer to having acoramidis available as a treatment for the ATTR-CM community,” said Isabelle Lousada, president and CEO of the Amyloidosis Research Consortium, a global nonprofit organization dedicated to advancements in amyloidosis.

The Company also received acceptance of its Marketing Authorization Application with the European Medicines Agency and is preparing for additional global regulatory submissions.

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

Bridgebio Pharma Announces U.S. Food and Drug Administration (FDA) Acceptance of New Drug Application (NDA) for Acoramidis for the Treatment of Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Amneal Announces Complete Response Resubmission for IPX203 New Drug Application

Amneal Pharmaceuticals, Inc. (NASDAQ: AMRX) (“Amneal” or the “Company”) today announced that it has provided a Complete Response resubmission to the U.S. Food and Drug Administration (FDA) for IPX203, a novel, oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules for the treatment of Parkinson’s disease (PD).

Carbidopa

levodopa 

The original NDA for IPX203 resulted in a Complete Response Letter (CRL) from FDA. The resubmission package included data from a healthy volunteer study which was conducted in the fourth quarter of 2023. The FDA did not request any other studies.

“We are pleased to provide our complete response resubmission for IPX203 as we look to expand our Parkinson’s franchise,” said Chirag and Chintu Patel, Co-Chief Executive Officers at Amneal. “We look forward to launching this much-needed treatment in the second half of 2024, subject to FDA approval.”

About IPX203 

IPX203 is a novel, oral formulation of CD/LD extended-release capsules designed for the treatment of Parkinson’s disease. IPX203 contains immediate-release granules and extended-release coated beads. The IR granules consist of CD and LD, with a disintegrant polymer to allow for rapid dissolution. The ER beads consist of LD, coated with a sustained release polymer to allow for slow release of the drug a mucoadhesive polymer to keep the granules adhered to the area of absorption longer, and an enteric coating to prevent the granules from disintegrating prematurely in the stomach. This formulation is distinct from RYTARY® (carbidopa/levodopa) extended-release capsules, Amneal’s extended-release CD/LD treatment for PD approved by the U.S. FDA in 2015.

About Parkinson’s Disease

Parkinson’s disease has become the fastest growing neurological disorder worldwide, with approximately 1 million patients diagnosed in the U.S. It is a progressive disorder of the central nervous system (CNS) that affects dopamine-producing neurons in the brain that affect movement.

PD is characterized by slowness of movement, stiffness, resting tremor and impaired balance.  While PD is not considered a fatal disease, it is associated with significant morbidity and disability.  The average age at diagnosis for patients with PD is 60; as people live longer, the number of patients living with PD is predicted to grow significantly over the coming decades. 

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

https://en.wikipedia.org/wiki/L-DOPA

Amneal Announces Complete Response Resubmission for IPX203 New Drug Application

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