FDA Approves DefenCath (taurolidine and heparin) to Reduce the Incidence of Catheter-Related Bloodstream Infections in Adult Hemodialysis Patients

CorMedix Inc. (Nasdaq: CRMD), a biopharmaceutical company focused on developing and commercializing therapeutic products for the prevention and treatment of life-threatening diseases and conditions, announced  the U.S. Food and Drug Administration (FDA)  approval of  DefenCath® (taurolidine and heparin) catheter lock solution (CLS) to reduce the incidence of catheter-related bloodstream infections (CRBSIs) for the limited population of adult patients with kidney failure receiving chronic hemodialysis through a central venous catheter (CVC). DefenCath is the first and only FDA-approved antimicrobial CLS in the U.S. and was shown to reduce the risk of CRBSIs by up to 71% in a Phase 3 clinical study.

Joseph Todisco, Chief Executive Officer of CorMedix commented, “The approval of DefenCath marks a major advancement in reducing life-threatening infections for patients receiving hemodialysis via central venous catheters and an important milestone for CorMedix. As the first FDA-approved antimicrobial catheter lock solution designed to prevent CRBSIs, DefenCath offers healthcare providers an option to reduce the risk of infections in a patient population already vulnerable due to underlying kidney failure. We thank all the patients, caregivers, clinical investigators, and our employees who have played an integral role in the development and regulatory approval of DefenCath. Our commercial team along with our broader organization is preparing for commercial launch, and we look forward to working with healthcare providers and facilities to give hemodialysis patients access to DefenCath in early 2024.”

The FDA approval of DefenCath was supported by results from the randomized, double-blind, active control, multicenter pivotal Phase 3 LOCK-IT-100 clinical trial designed to assess the efficacy and safety of DefenCath for reducing the incidence of CRBSIs in patients with kidney failure receiving chronic hemodialysis. In the study, a total of 806 subjects were randomized to receive either DefenCath or heparin as a CLS. Patients in the DefenCath group had a lower incidence of CRBSI events compared to patients in the control group. The Hazard Ratio was 0.29, corresponding to a statistically significant 71% reduction in risk of developing a CRBSI. An independent Data Safety and Monitoring Board recommended an early termination of the study based on demonstrated efficacy and a pre-specified level of statistical significance with no safety concerns. Adverse events were comparable to control.

Edward V. Hickey, III, President of the American Association of Kidney Patients and Chair of the Veterans Health Initiative stated, “Patients and their loved ones have faced many burdens related to kidney failure, including complications caused by catheter related bloodstream infections and associated loss of work, severe disability and death. Until now, patients who need hemodialysis via a central venous catheter have had little choice other than to accept high infection risks associated with the existing standard of care. The FDA’s approval of DefenCath is a meaningful moment for patients and their healthcare providers because they now have a new alternative to reduce the risks of CRBSIs.” Mr. Hickey is a kidney patient, former senior staff member of the U.S. Congress and has served in two presidential administrations.

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

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

FDA Approves DefenCath (taurolidine and heparin) to Reduce the Incidence of Catheter-Related Bloodstream Infections in Adult Hemodialysis Patients

FDA Approves Truqap (capivasertib) plus Faslodex for Patients with Advanced HR-Positive Breast Cancer

AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in the US for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN). Eligible patients will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.

The approval by the Food and Drug Administration (FDA) was based on the results from the CAPItello-291 Phase III trial published earlier this year in The New England Journal of Medicine.1 In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).

Breast cancer is the most common cancer and one of the leading causes of cancer-related death worldwide.2 HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype, with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting up to 50% of patients with advanced HR-positive breast cancer.4-6 Endocrine therapies are widely used in this setting, but many patients develop resistance to 1st-line cyclin-dependent kinase (CDK) 4/6 inhibitors and estrogen receptor-targeting therapies, underscoring the need for additional endocrine therapy-based options

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

FDA Approves Truqap (capivasertib) plus Faslodex for Patients with Advanced HR-Positive Breast Cancer

FDA Approves Ogsiveo (nirogacestat) for Adults with Desmoid Tumors

SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced  the U.S. Food and Drug Administration (FDA) approval of  Ogsiveo™ (nirogacestat), an oral gamma secretase inhibitor, for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. The FDA previously granted breakthrough therapy, fast track and orphan drug designations to nirogacestat for the treatment of desmoid tumors.

“Our team is honored to deliver the first FDA-approved therapy for patients with desmoid tumors. This community has been waiting for an effective treatment that not only shrinks their tumors but also significantly improves pain, which is the most debilitating symptom reported by people living with desmoid tumors,” said Saqib Islam, Chief Executive Officer of SpringWorks. "We are pleased with the broad label, which includes all progressing adult patients and specifically references improvement in pain, and believe Ogsiveo has the potential to become the new standard of care for people living with these devastating tumors. This is a watershed moment for the desmoid tumor community, and we would like to extend our gratitude to the patients, families, investigators, and advocacy groups involved in the journey to making Ogsiveo available in the U.S.”

Desmoid tumors are locally aggressive and invasive soft-tissue tumors that can lead to substantial morbidity.2,3 In addition, when vital structures are impacted, desmoid tumors can be life-threatening.3 Although they do not metastasize, desmoid tumors are often refractory to existing off-label systemic therapies and associated with recurrence rates of up to 77% following surgical resection.4-6 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.6

“Desmoid tumors can have a significant impact on people’s lives and are difficult to manage due to their invasive nature and high rates of recurrence. Ogsiveo is a highly innovative therapy with efficacy data demonstrating both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms,” said Mrinal M. Gounder, M.D., sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center (MSK) in New York City and an investigator in the Phase 3 DeFi trial. “As a treating physician, it was encouraging to see in the DeFi trial that Ogsiveo achieved statistically significant and clinically meaningful improvements across the primary and all key secondary endpoints, while also having a manageable safety profile. This approval represents an important therapeutic advance for patients.”

more at 

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

FDA Approves Ogsiveo (nirogacestat) for Adults with Desmoid Tumors

FDA Approves Fabhalta (iptacopan) for the Treatment of Adults with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Novartis announced the U.S. Food and Drug Administration (FDA) approval of  Fabhalta® (iptacopan) as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH)1. Fabhalta is a Factor B inhibitor that acts proximally in the alternative complement pathway of the immune system, providing comprehensive control of red blood cell (RBC) destruction within and outside the blood vessels (intra- and extravascular hemolysis [IVH and EVH]). In clinical trials, treatment with Fabhalta increased hemoglobin levels (≥ 2 g/dL from baseline in the absence of RBC transfusions) in the majority of patients and in APPLY-PNH nearly all patients treated with Fabhalta did not receive blood transfusions.

“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” said Vinod Pullarkat, MD, MRCP, Clinical Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope. “In clinical studies, iptacopan was superior to anti-C5s in hemoglobin improvement in the absence of RBC transfusion and transfusion avoidance rate, and also effective in complement inhibitor-naïve individuals, by providing clinically meaningful hemoglobin-level increases without the need for blood transfusions.”

The FDA approval is based on the Phase III APPLY-PNH trial in patients with residual anemia (hemoglobin < 10 g/dL) despite prior anti-C5 treatment who switched to Fabhalta, which demonstrated superiority in hemoglobin improvement in the absence of RBC transfusions and in transfusion avoidance rate over patients who stayed on anti-C5 treatments1,2. Approval was also supported by the Phase III APPOINT-PNH study in complement inhibitor-naïve patients1,3. The 24-week core treatment periods in APPLY-PNH and APPOINT-PNH trials respectively showed

More at 

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

FDA Approves Fabhalta (iptacopan) for the Treatment of Adults with Paroxysmal Nocturnal Hemoglobinuria (PNH)

FDA Approves iDose TR (travoprost intracameral implant) for the Treatment of Glaucoma

Glaukos Corporation (NYSE: GKOS), an ophthalmic medical technology and pharmaceutical company focused on novel therapies for the treatment of glaucoma, corneal disorders and retinal diseases, announced   the U.S. Food and Drug Administration (FDA) approval of its New Drug Application (NDA) for a single administration per eye of iDose® TR (travoprost intracameral implant) 75 mcg, a prostaglandin analog indicated for the reduction of intraocular pressure (IOP) in patients with ocular hypertension (OHT) or open-angle glaucoma (OAG).

“With the next generation of procedural pharmaceutical solutions for glaucoma such as iDose TR, we now have a new tool that will confront the standard legacy practice of relying on topical drops, which are known to cause uncomfortable side effects and present a myriad of challenges such as treatment adherence, complex dosing regimens, and difficulty with self-administration,” said John Berdahl, MD, clinician and researcher at Vance Thompson Vision. “The clinical data suggest that iDoseTR is not only effective with a favorable safety profile, but it has potential to relieve patients from the burdens of prescription eye drops for an extended period of time. I look forward to adding this novel therapy into my treatment toolbox for the benefit of my patients.”

The FDA approval is based on results from two prospective, randomized, multicenter, double-masked, Phase 3 pivotal trials (GC-010 and GC-012) designed to compare the safety and efficacy of a single administration of one of two iDose TR models with different travoprost release rates (referred to as the fast- and slow-release iDose TR models, respectively) to topical timolol ophthalmic solution, 0.5% BID (twice a day), in reducing IOP in subjects with open-angle glaucoma or ocular hypertension. In total, the Phase 3 trials randomized 1,150 subjects across 89 clinical sites. The FDA approval and Phase 3 data referenced below is for the slow-release iDose TR model, consistent with the company’s NDA submission and commercialization plans.

Both Phase 3 trials successfully achieved the pre-specified primary efficacy endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months. IOP reductions from baseline over the first 3 months were 6.6-8.4 mmHg in the iDose TR arm, versus 6.5-7.7 mmHg in the timolol control arm (mmHg range represents IOP reduction means across the six U.S. FDA pre-specified timepoints of 8 a.m. and 10 a.m. at Day 10, Week 6 and Month 3). Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated non-inferiority to timolol ophthalmic solution in IOP reduction during the first 3 months. The FDA also noted that subsequently iDose TR did not demonstrate non-inferiority over the next 9 months.

iDose TR is a first-of-its-kind, long-duration, intracameral procedural pharmaceutical therapy designed to continuously deliver 24/7 therapeutic levels of a proprietary formulation of travoprost inside the eye for extended periods of time. iDose TR is intended to improve the standard of care by addressing the ubiquitous patient non-compliance issues and chronic side effects associated with topical glaucoma medications.

“The FDA approval of iDose TR represents a significant milestone for Glaukos following an extensive pioneering journey since the inception of the original idea nearly 15 years ago. Today’s approval ushers in a new era of interventional glaucoma therapy by enabling a more proactive and reliable approach for patients in need,” said Thomas Burns, Glaukos chairman and chief executive officer. “We believe iDose TR can be a transformative, novel technology able to fundamentally improve the treatment paradigm for patients with open-angle glaucoma or ocular hypertension. We are grateful to the clinical investigators and study participants in the clinical trials for their instrumental roles in helping us reach this important advancement for glaucoma patient care. At Glaukos, we are relentlessly focused on delivering novel therapies for chronic eye diseases and now iDoseTR has the potential to redefine the standard of care for patients in the U.S. affected by open-angle glaucoma and ocular hypertension.”

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

FDA Approves iDose TR (travoprost intracameral implant) for the Treatment of Glaucoma

FDA Approves Iwilfin (eflornithine) as Maintenance Therapy for High-Risk Neuroblastoma

USWM, LLC  announced the U.S. Food and Drug Administration (FDA)  approval of Iwilfin ™ (eflornithine) 192 mg tablets, a groundbreaking oral maintenance therapy for high-risk neuroblastoma. Iwilfin is indicated to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma who have demonstrated at least a partial response to prior multiagent, multimodality therapy, including anti-GD2 immunotherapy.

Acc

ording to the American Cancer Society, 700-800 cases of neuroblastoma are diagnosed in the U.S. each year, with 90% of diagnoses coming before age 5. Over 50% of these cases are classified as high-risk. High-risk neuroblastoma is a challenging disease, with a high mortality rate driven primarily by the risk of relapse after achieving remission. Approximately half of children with high-risk neuroblastoma do not survive beyond five years from diagnosis. Although existing treatments are effective in helping patients achieve remission, patients lack options to sustain it. Avoiding relapse is crucial to improving survival rates.

“We are thrilled to announce the FDA approval of Iwilfin , which provides a new and much-needed treatment option for children with high-risk neuroblastoma,” said Breck Jones, Chief Executive Officer of US WorldMeds. “The goal for treating these young patients is to prevent relapse, and advancing therapeutic options is critical to this mission. Iwilfin offers new hope and improved outcomes for these vulnerable children.”

Iwilfin is taken orally, with or without food, twice daily for two years. Iwilfin is generally well-tolerated, with side effects typically manageable through dose modifications. The most common side effects are hearing loss, otitis media, pyrexia, pneumonia, and diarrhea. Important Safety Information can be found below.

US WorldMeds partnered with the Beat Childhood Cancer Research Consortium at Penn State University, which conducted the preclinical and clinical research to help advance this vital therapy. The Consortium represents a group of over 50 hospitals that offer collaboration through a network of childhood cancer clinical trials.

“Our partnerships were instrumental in bringing Iwilfin through the FDA registration process,” said Kristen Gullo, Vice President of Development and Regulatory Affairs at US WorldMeds. “We are thankful for the dedication of our partners, specifically the Beat Childhood Cancer Research Consortium, who work tirelessly to improve treatment outcomes for pediatric cancer patients. This FDA approval represents a beacon of hope for the high-risk neuroblastoma community and a significant step forward in the fight against this devastating disease.”

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

FDA Approves Iwilfin (eflornithine) as Maintenance Therapy for High-Risk Neuroblastoma

FDA Approves Wainua (eplontersen) for the Treatment of Adults with Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis

Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced  the U.S. Food and Drug Administration (FDA)   approval of  Ionis and AstraZeneca's Wainua™ (eplontersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, commonly referred to as hATTR-PN or ATTRv-PN. Wainua is the only approved medicine for the treatment of ATTRv-PN that can be self-administered via an auto-injector.

"Many people living with hereditary transthyretin-mediated amyloid polyneuropathy are unable to fully enjoy their lives because of the relentless, progressive and debilitating  effects of the disease," said Michael J. Polydefkis, M.D., professor of neurology at Johns Hopkins University School of Medicine and an investigator in the NEURO-TTRansform study. "Approval of Wainua represents a meaningful advancement in treatment, one that gives those who are living with transthyretin-mediated amyloid polyneuropathy help managing the disease."

ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade. Wainua is a ligand-conjugated antisense oligonucleotide (LICA) medicine designed to reduce the production of TTR protein at its source.

"The FDA approval of Wainua marks an important milestone for people living with hereditary transthyretin-mediated amyloid polyneuropathy, who will now have an effective, well-tolerated treatment that can be self-administered via auto-injector to combat this devastating disease," said Brett P. Monia, Ph.D., chief executive officer at Ionis. "It is also a pivotal moment for Ionis as Wainua will be the first in a steady cadence of potential commercial launches for the company. We are proud to have discovered and, together with AstraZeneca, developed Wainua, and are grateful to the patients, caregivers and investigators who participated in our clinical studies, as well as for the dedication of our scientists and researchers."

"People with hereditary transthyretin-mediated amyloid polyneuropathy, and other forms of amyloidosis, are often misdiagnosed since symptoms can mirror other conditions," said Isabelle Lousada, President and CEO, Amyloidosis Research Consortium "The path to getting an accurate diagnosis can often be a long, arduous journey and it is critical that a timely and accurate diagnosis is made not only for the individual experiencing symptoms but for their families and loved ones. It is exciting to see new innovations coming through and increased efforts to raise awareness in an area that has often been overlooked or neglected."

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

Ref : https://go.drugbank.com/drugs/DB16199

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FDA Approves Wainua (eplontersen) for the Treatment of Adults with Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis

FDA Approves Zelsuvmi (berdazimer topical gel) for the Treatment of Molluscum Contagiosum

Ligand Pharmaceuticals Incorporated (NASDAQ: LGND)  announced  the U.S. Food and Drug Administration (FDA)  approval of Zelsuvmi™ (berdazimer topical gel, 10.3%) for the treatment of molluscum contagiosum (molluscum) in adults and pediatric patients one year of age and older.i The FDA approved Zelsuvmi as the first novel drug for the treatment of molluscum infections.

Zelsuvmi is the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home, outside of a physician's office, or other medical setting to treat this highly contagious viral skin infection.

“The approval of Zelsuvmi is a breakthrough, marking the first time that clinicians can treat molluscum with an efficacious topical prescription medication that is applied by the patient, or a family member,” said Mark D. Kaufmann, MD, FAAD, a Clinical Professor of Dermatology in the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City and Past President of the American Academy of Dermatology. “I look forward to having this novel medication to treat my molluscum patients.”

Molluscum is a highly contagious viral skin infection characterized by skin-colored to red lesions with a central, umbilicated viral core.ii Approximately 6 million Americans, primarily children, are infected each year.iii,iv However, up to 73% of children go untreated.v Treating the lesions is critical to preventing the viral infection from spreading to other people or to other areas of the body. vi

“It is nice to see that molluscum contagiosum is finally getting the attention it deserves. For those of us in the primary care field, it is wonderful to have an effective option that can be used at home rather than taking a wait and watch approach,” said Stephen W. Stripling, MD, Pediatrician, Study Investigator and Molluscum Researcher.

Zelsuvmi is a nitric oxide releasing agent. Nitric oxide has been shown to have antiviral properties.vii The mechanism of action of Zelsuvmi for the treatment of molluscum contagiosum is unknown. Nevertheless, Zelsuvmi's efficacy was demonstrated in 2 Phase 3 trials - B-SIMPLE 4 and B-SIMPLE 2. These trials showed Zelsuvmi's ability to reduce lesion counts and was well tolerated when used once a day.viii The B-SIMPLE Phase 3 program enrolled 1,598 patients.ix The most commonly reported adverse reactions (≥1%) in clinical trials were application site reactions. See additional Important Safety Information for Zelsuvmi below.

“We are proud of the team’s accomplishment, having completed the world’s largest clinical program in molluscum to bring this first-in-class topical medication to FDA approval,” said Todd Davis, CEO of Ligand. “Pediatricians, dermatologists, and caregivers have long-sought a convenient approach to treat this highly contagious skin infection. With Zelsuvmi, patients now have an at-home treatment option available.”

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

FDA Approves Filsuvez () Topical Gel for the Treatment of Epidermolysis Bullosa

Chiesi Group  announced   the U.S. Food and Drug Administration (FDA) approval of  Filsuvez® (birch triterpenes) topical gel for the treatment of partial thickness wounds in patients 6 months and older with Junctional Epidermolysis Bullosa (JEB) and Dystrophic Epidermolysis Bullosa (DEB). Filsuvez is the first approved treatment for wounds associated with JEB, a rare, moderate-to-severe form of EB with blisters beginning in infancy. Filsuvez joined the Chiesi portfolio as part of the agreement reached during the acquisition of Amryt Pharma in January of this year.

EB is a debilitating inherited skin disease that causes a person’s skin to be so fragile it can be injured just from touch. This rare, chronic, and distressing disorder affects infants, children and adults and is intensely painful; recurrent blistering and chronic wounds can result in intolerable pain with limited mobility. Living with EB entails daily challenges to navigate, including slow-healing wounds at risk of infection and painful dressing changes.

More...

https://www.blogger.com/blog/post/edit/6520560265126950473/4125302301208965400

FDA Approves Daybue (trofinetide) for the Treatment of Rett Syndrome

In continuation of my update on trofinetide

Acadia Pharmaceuticals Inc. (Nasdaq: ACAD)  announced  the U.S. Food and Drug Administration (FDA)  approval of  Daybue (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. Daybue is the first and only drug approved for the treatment of Rett syndrome.

“Today marks an important milestone for the Rett community and Acadia. As the first FDA-approved drug for the treatment of Rett syndrome, Daybue now offers the potential to make meaningful differences in the lives of patients and their families who have lacked options to treat the diverse and debilitating array of symptoms caused by Rett syndrome,” said Steve Davis, Acadia’s Chief Executive Officer. “We are grateful to all of the Rett syndrome patients, caregivers, clinical investigators and our employees who have contributed to making today a reality and look forward to getting Daybue to patients as quickly as possible.”

“Rett syndrome is a profoundly debilitating and complex, rare, neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms throughout the course of a patient’s life,” said Jeffrey L. Neul, M.D., Ph.D., Annette Schaffer Eskind Chair and Director, Vanderbilt Kennedy Center, Professor of Pediatrics, Division of Neurology, Pharmacology, and Special Education, Vanderbilt University Medical Center and Phase 3 LAVENDER™ study investigator. “Now, for the first time after decades of clinical research, healthcare providers finally have a treatment option to address a range of core behavioral, communication and physical symptoms for their patients living with Rett syndrome.”

Rett syndrome is a complex, rare, neurodevelopmental disorder typically caused by a genetic mutation on the MECP2 gene.2,3 It is characterized by a period of normal development until six to 18 months of age, followed by significant developmental regression with loss of acquired communication skills and purposeful hand use. Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities. Rett syndrome is believed to affect 6,000 to 9,000 patients in the U.S., with a diagnosed population of approximately 4,500 U.S. patients.

The FDA approval of Daybue was supported by results from the pivotal Phase 3 LAVENDER study evaluating the efficacy and safety of trofinetide versus placebo in 187 female patients with Rett syndrome five to 20 years of age. In the study, treatment with Daybue demonstrated statistically significant improvement compared to placebo on both co-primary efficacy endpoints, as measured by the change from baseline in Rett Syndrome Behaviour Questionnaire (RSBQ) total score (p=0.018) and the Clinical Global Impression-Improvement (CGI-I) scale score (p=0.003) at week 12. The RSBQ is a caregiver assessment that evaluates a range of symptoms of Rett syndrome including vocalizations, facial expressions, eye gaze, hand movements (or stereotypies), repetitive behaviors, breathing, night-time behaviors and mood. The CGI-I is a global physician assessment of whether a patient has improved or worsened. In the study, the most common side effects were diarrhea (82%) and vomiting (29%).

“This is a historic day for the Rett syndrome community and a meaningful moment for the patients and caregivers who have eagerly awaited the arrival of an approved treatment for this condition,” said Melissa Kennedy, Chief Executive Officer of the International Rett Syndrome Foundation. “Rett syndrome is a complicated, devastating disease that affects not only the individual patient, but whole families. With today’s FDA decision, those impacted by Rett have a promising new treatment option that has demonstrated benefit across a variety of Rett symptoms, including those that impact the daily lives of those living with Rett and their loved ones.”

FDA Approves Daybue (trofinetide) for the Treatment of Rett Syndrome

FDA Approves Zavzpret (zavegepant) Nasal Spray for the Acute Treatment of Migraine

Pfizer Inc. (NYSE: PFE)  announced the U.S. Food and Drug Administration (FDA)  approval of Zavzpret (zavegepant), the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for the acute treatment of migraine with or without aura in adults. In its pivotal Phase 3 study, Zavzpret was statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at two hours post-dose. The pivotal study also demonstrated pain relief as early as 15 minutes in a prespecified secondary endpoint versus placebo.

“The FDA approval of Zavzpret marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications,” said Angela Hwang, Chief Commercial Officer, President, Global Biopharmaceuticals Business, Pfizer. “Zavzpret underscores Pfizer’s commitment to delivering an additional treatment option to help people with migraine gain relief and get back to their daily lives. Pfizer will continue to build its migraine franchise to further support the billions of people worldwide impacted by this debilitating disease.”

The FDA approval is based on two pivotal randomized, double-blind, placebo-controlled studies that established the efficacy, tolerability and safety profiles of Zavzpret for the acute treatment of migraine. In these studies, Zavzpret was statistically superior to placebo on the co-primary endpoints of pain freedom (defined as a reduction of moderate or severe headache pain to no headache pain) and freedom from most bothersome symptom at two hours post-dose (defined as the absence of the self-identified most bothersome symptom). The pivotal Phase 3 study published in The Lancet Neurology found Zavzpret showed broad efficacy by also demonstrating statistically significant superiority to placebo across 13 of 17 prespecified secondary outcome measures, including early time point endpoints (e.g., 15 and 30-minute pain relief and return to normal function at 30 minutes), return to normal function at 2 hours, and durable efficacy endpoints (e.g., 2-24 and 2-48 hour sustained pain freedom and sustained pain relief). On the 14th endpoint, return to normal function at 15 minutes post-dose, the difference between Zavzpret and placebo was not significant. Consequently, in keeping with the trial’s statistical analysis plan, the remaining secondary endpoints were not formally tested.

“When a migraine hits, it has a significant negative impact on a person’s daily life,” said Kathleen Mullin, M.D., Associate Medical Director at New England Institute for Neurology & Headache. “Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works. As a nasal spray with rapid drug absorption, Zavzpret offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting, so they can get back to normal function quickly.”

Zavzpret was well tolerated in clinical trials. The most common adverse reactions reported in at least 2% of patients treated with Zavzpret and at a frequency greater than placebo were taste disorders (includes dysgeusia and ageusia), nausea, nasal discomfort and vomiting. Zavzpret is contraindicated in patients with a history of hypersensitivity to zavegepant or to any of its components. Hypersensitivity reactions, including facial swelling and urticaria, have occurred with Zavzpret in clinical studies. 

 https://en.wikipedia.org/wiki/Zavegepant#/media/File:Zavegepant.svg

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

FDA Approves Zavzpret (zavegepant) Nasal Spray for the Acute Treatment of Migraine

FDA Approves Skyclarys (omaveloxolone) for the Treatment of Friedreich’s Ataxia

In continuation of my update on omaveloxolone

Reata Pharmaceuticals, Inc. (Nasdaq: RETA) announced   the U.S. Food and Drug Administration (“FDA”) approval of  Skyclarys™ (omaveloxolone) for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 years and older. With this approval, the FDA granted a rare pediatric disease priority review voucher.

"The approval of Skyclarys, the first therapy specifically indicated for the treatment of Friedreich’s ataxia, is an important milestone for patients affected by this disease as well as their families and caregivers," said Warren Huff, Reata's Chief Executive Officer. "We are grateful to Friedreich’s ataxia patients, investigators, U.S. regulators, and our scientists and employees who made this approval possible. As a company, this is a transformative milestone that highlights our commitment to developing and commercializing novel therapies for patients with severe diseases with few or no approved therapies. We look forward to delivering Skyclarys to eligible patients as quickly as possible."

Friedreich’s ataxia is an ultra-rare, inherited neurodegenerative disorder that is typically diagnosed during adolescence. Patients with Friedreich’s ataxia experience progressive loss of coordination, muscle weakness, and fatigue, which commonly progresses to motor incapacitation and wheelchair reliance by their teens or early twenties, and eventually death. Friedreich’s ataxia affects approximately 5,000 diagnosed patients in the U.S.

“Friedreich's ataxia is a debilitating neuromuscular disease that progressively robs patients of their mobility and independence,” said Susan Perlman, MD, Clinical Professor, Department of Neurology, David Geffen School of Medicine, UCLA. “The approval of Skyclarys represents an important step forward in the treatment of Friedreich's ataxia, providing physicians with the first disease-specific treatment option approved for patients living with this ultra-rare and progressive disease.”

"Today’s approval of Skyclarys represents a significant milestone in our effort to advance research and achieve treatments for Friedreich’s ataxia," said Jen Farmer, Chief Executive Officer at Friedreich's Ataxia Research Alliance. "The entire Friedreich's ataxia community including patients, clinicians, scientists, pharmaceutical companies, government agencies, and others have worked collaboratively for decades to enable therapeutic development for this debilitating disease. Today, we celebrate the impact of an engaged patient community, and we are grateful to the FDA and Reata for working together on the approval of Skyclarys, the first therapy approved in the United States for adult and adolescent patients aged 16 years and older with Friedreich's ataxia.”

The approval of Skyclarys is supported by the efficacy and safety data from the MOXIe Part 2 trial and a post hoc Propensity-Matched Analysis of the open-label MOXIe Extension trial.

MOXIe Part 2 was a randomized, double-blind, placebo-controlled study. Patients with genetically confirmed Friedreich’s ataxia and baseline modified Friedreich’s Ataxia Rating Scale (“mFARS”) scores between 20 and 80 were randomized 1:1 to receive placebo or 150 mg of Skyclarys daily. The primary endpoint was change from baseline in mFARS score compared to placebo at Week 48 in the Full Analysis Population of patients without severe pes cavus (n=82). The mFARS is a clinical assessment tool to assess patient function and is used in clinical trials to assess the efficacy of investigational products for use in Friedreich’s ataxia. Treatment with Skyclarys resulted in statistically significant lower mFARS scores (less impairment) relative to placebo at Week 48. The placebo-corrected difference between the two groups was -2.41 points with a p-value of 0.0138. The most common adverse reactions in MOXIe Part 2 (≥20% and greater than placebo) were elevated liver enzymes (AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and musculoskeletal pain.

Further, in a post hoc Propensity-Matched Analysis, mFARS progression of patients treated with 150 mg of Skyclarys daily in the open-label MOXIe Extension trial was compared to the progression of propensity score-matched untreated patients in the largest natural history study of Friedreich’s ataxia, Clinical Outcome Measures in Friedreich’s ataxia (“FA-COMS”). All patients enrolled in the MOXIe Extension study with at least one post-baseline assessment (n=136) were matched one to one with patients from the FA-COMS study (n=136). Lower (improved) mFARS scores were observed in patients treated with Skyclarys after 3 years relative to the matched set of untreated patients from the FA-COMS natural history study. These exploratory analyses should be interpreted cautiously given the limitations of data collected outside of a controlled study, which may be subject to confounding.

FDA Approves Skyclarys (omaveloxolone) for the Treatment of Friedreich’s Ataxia

FDA Approves Rezzayo (rezafungin for injection) for the Treatment of Candidemia and Invasive Candidiasis

In continuation of my update on rezafungin

Cidara Therapeutics, Inc.   and Melinta Therapeutics, LLC  announced   the U.S. Food and Drug Administration (FDA) approval of  Rezzayo (rezafungin for injection) for the treatment of candidemia and invasive candidiasis in adults with limited or no alternative treatment options. Rezzayo is the first new treatment option approved for patients with candidemia and invasive candidiasis in over a decade.

“The FDA approval of Rezzayo represents a significant milestone for Cidara, and for patients confronted with difficult-to-treat and often deadly candidemia and invasive candidiasis,” said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara. “I am extremely proud of all of the Cidara employees who collectively advanced Rezzayo from preclinical development to NDA approval and am grateful to the many patients and healthcare teams who have participated in the clinical studies.”

George Thompson, M.D., principal investigator in the ReSTORE trial and professor of clinical medicine at the University of California, Davis, School of Medicine, added, “The FDA approval of Rezzayo is tremendous news for those of us who have been hoping for a new option to treat our patients with these deadly fungal infections. Based on the totality of clinical data generated, Rezzayo has the potential to simplify the management of invasive candidiasis and enhance the continuity of echinocandin care.”

The FDA approval of once-weekly Rezzayo was based on clinical data from Cidara’s global ReSTORE Phase 3 trial and supported by the STRIVE Phase 2 clinical trial and extensive non-clinical development program. In clinical studies, Rezzayo, dosed once-weekly, met the FDA and EMA primary endpoints, demonstrating statistical non-inferiority versus caspofungin, a current once-daily standard of care. In addition, overall rates of adverse events and serious adverse events were comparable in patients receiving Rezzayo and caspofungin, while rates of adverse events leading to study drug discontinuation were also similar for Rezzayo and caspofungin. Based on Qualified Infectious Disease Product (QIDP) designation, Rezzayo was approved under Priority Review.

Christine Ann Miller, president and chief executive officer of Melinta Therapeutics, added, “We are thrilled that the FDA has approved Rezzayo, and are firmly committed to offering this innovative therapy to address unmet medical needs and simplify the treatment for patients suffering from invasive Candida infections. We intend to leverage our expansive commercial infrastructure and experience launching anti-infective drugs into acute care settings. We are working closely with Cidara and anticipate bringing Rezzayo, a differentiated once-weekly treatment to patients, this summer.”

Last year, Melinta announced that it had acquired the exclusive rights to commercialize Rezzayo in the U.S. from Cidara. Cidara retains the rights to rezafungin in Japan and has licensed the commercial rights to Melinta Therapeutics in the U.S. and Mundipharma in all other geographies. The European Medicines Agency (EMA) accepted the marketing authorization application (MAA) for rezafungin in August 2022 and it is currently under review.

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

FDA Approves Rezzayo (rezafungin for injection) for the Treatment of Candidemia and Invasive Candidiasis

FDA Approves Brenzavvy (bexagliflozin) for the Treatment of Adults with Type 2 Diabetes

TheracosBio  announced  the U.S. Food and Drug Administration (FDA)   approval of  Brenzavvy (bexagliflozin), an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor. Brenzavvy is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Brenzavvy is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Brenzavvy is contraindicated in patients who are hypersensitive to bexagliflozin or any tablet ingredient and is not indicated for the treatment of type 2 diabetes in patients with end stage renal disease or who are receiving dialysis.

The FDA approval is based on results from a clinical program that evaluated the safety and efficacy of Brenzavvy in 23 clinical trials enrolling more than 5,000 adults with type 2 diabetes mellitus. Phase 3 studies showed Brenzavvy significantly reduced hemoglobin A1c and fasting blood sugar after 24 weeks, either as a monotherapy, in combination with metformin, or as an add-on to standard-of-care treatment consisting of a variety of regimens, including metformin, sulfonylureas, insulin, DPP4 inhibitors, or combinations of these agents. Although Brenzavvy is not approved for weight or blood pressure reduction, modest decreases in both weight and systolic blood pressure have been observed in the clinical program.

“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Dr. Mason Freeman, M.D., Director of the Translational Research Center at Massachusetts General Hospital. “Being involved in all of the clinical trials for Brenzavvy, I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”

Brenzavvy treatment can be initiated in adults with type 2 diabetes with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m2. Patients with eGFR less than 60 and greater than 30 mL/min/1.73 m2 are said to be in stage 3 chronic kidney disease, and for these patients metformin is often avoided due to the risk of lactic acidosis.

“Today's FDA approval represents a significant milestone for TheracosBio and provides an important treatment option to patients who suffer from type 2 diabetes. We look forward to bringing Brenzavvy to market,” said Albert R. Collinson, Ph.D., President and CEO of TheracosBio. “The approval of the Brenzavvy NDA is a result of the tireless work of the TheracosBio team and investigators. I want to thank all of the patients who took part in our clinical trials.”

According to the U.S. Centers for Disease Control and Prevention, more than 33 million Americans have type 2 diabetes, which means their bodies don’t use insulin correctly and as a result their blood sugar levels are too high. While some people can control their blood sugar levels with exercise and a healthy diet, others may need additional help to achieve good blood sugar (glycemic) control.

SGLT2 inhibitors are a class of prescription medicines that lower blood sugar by causing the kidneys to remove sugar from the body through urine.

Brenzavvy is available as 20 mg oral tablets recommended to be taken once daily, in the morning with or without food.

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

FDA Approves Brenzavvy (bexagliflozin) for the Treatment of Adults with Type 2 Diabetes

FDA Approves Jaypirca (pirtobrutinib) for Adult Patients with Relapsed or Refractory Mantle Cell Lymphoma

Loxo@Lilly, the oncology unit of Eli Lilly and Company (NYSE: LLY),  announced the U.S. Food and Drug Administration (FDA) approved Jaypirca™ (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. Jaypirca was approved under the FDA's Accelerated Approval pathway based on response rate from the open-label, single-arm, international, Phase 1/2 study, called the BRUIN trial.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Jaypirca, a highly selective kinase inhibitor, utilizes a novel binding mechanism and is the first and only FDA approved non-covalent (reversible) BTK inhibitor. Jaypirca can reestablish BTK inhibition in MCL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the BTK pathway.

"The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent BTK inhibitor," said Michael Wang, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "These data indicate that Jaypirca can provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time patients may benefit from BTK inhibition therapy. Jaypirca offers a new approach to targeting the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients."

The labeling for Jaypirca contains warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, second primary malignancies, and embryo-fetal toxicity. See Important Safety Information below and full Prescribing Information for additional information, including dosing modifications.

"We are pleased to bring a meaningful new therapeutic option to patients with MCL that can reestablish the benefit of targeting the BTK pathway after receiving multiple prior therapies, including a covalent BTK inhibitor," said Jacob Van Naarden, chief executive officer, Loxo@Lilly. "We are grateful to the patients, investigators, and other members of the clinical care teams for their contributions. Our team has been committed to rapidly advancing the development of Jaypirca for patients with MCL, and we look forward to building on this milestone by continuing to bring forward important new treatments for people with hematologic malignancies."

The FDA approval is based on data from a subset of patients in the BRUIN Phase 1/2 trial. The assessment of efficacy was based on 120 patients with MCL treated with Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. Patients with active central nervous system lymphoma or allogeneic hematopoietic stem cell transplantation or CAR T-cell therapy within 60 days were excluded. Patients had received a median of three prior lines of therapy (range: 1 to 9), with 93% having two or more prior lines; all patients received one or more prior lines of therapy containing a covalent BTK inhibitor. Eighty-three percent (83%) of patients discontinued their last BTK inhibitor due to refractory or progressive disease. Efficacy was based on overall response rate (ORR) and duration of response (DOR) as assessed by an independent review committee (IRC) using 2014 Lugano criteria.

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https://en.wikipedia.org/wiki/Pirtobrutinib#/media/File:Pirtobrutinib.svg

FDA Approves Jaypirca (pirtobrutinib) for Adult Patients with Relapsed or Refractory Mantle Cell Lymphoma

FDA Approves Orserdu (elacestrant) for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer

The Menarini Group (“Menarini”), a leading Italian pharmaceutical and diagnostics company, announced  the U.S. Food and Drug Administration (FDA)   approval of  Orserdu for the treatment of postmenopausal women or adult men, with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Stemline Therapeutics (“Stemline”), a wholly-owned subsidiary of the Menarini Group, headquartered in New York and focused on bringing transformational oncology treatments for cancer patients, will commercialize Orserdu in the U.S.

“The FDA approval of Orserdu marks the first ever therapy for ER+, HER2- advanced or metastatic breast cancer patients with ESR1 mutations and we are very proud to offer a targeted therapy addressing this huge unmet need,” commented Elcin Barker Ergun, Chief Executive Officer of the Menarini Group. “We are grateful to the patients, investigators and administrators who participated in the clinical trials that led to this remarkable innovation.”

Orserdu is approved under the FDA’s Priority Review and Fast Track designation based on the results of the registrational Phase III trial EMERALD, that demonstrated statistically significant progression-free survival (PFS) with elacestrant vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane), meeting both primary endpoints in all patients and in those patients whose tumors harbor ESR1 mutations.

In the group of patients whose tumors had ESR1 mutations, elacestrant reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC. A post-hoc analysis of the PFS results based on the duration of prior CDK4/6i inhibitors (CDK4/6i) usage was presented at San Antonio Breast Cancer Symposium (SABCS) in December 2022. The median PFS was 8.6 months on elacestrant vs 1.9 months for SOC, in those patients whose tumors harbored ESR1 mutations and had been treated with a CDK4/6i for at least 12 months.

Safety data is consistent with the other endocrine therapies. Most of the adverse events (AEs), including nausea and musculoskeletal pain were grade 1 and 2. No hematological safety signal was observed and none of the patients in either of the two treatment arms had sinus bradycardia.

“Advanced or metastatic ER+, HER2- breast cancer pre-treated with endocrine-based therapy remains an area of unmet medical need. The last endocrine therapy approved was about 20 years ago, and effective endocrine options for this patient population are needed,” said Dr. Aditya Bardia, MD, MPH, Director of Breast Cancer Research at Mass General Cancer Center, Associate Professor at the Medicine Department at Harvard Medical School, and Principal Investigator for the EMERALD trial. “ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat. The approval of elacestrant is welcomed as it offers a novel option for patients with ER+, HER2- metastatic breast cancer. This therapy targets the ESR1 mutations in metastatic breast cancer and provides patients with a convenient oral once-daily dose.”

“Each year 300,000 Americans are diagnosed with breast cancer and metastatic breast cancer causes the vast majority of deaths from the disease: more than 43,000 annually. We urgently need new and better treatment options to extend and improve the lives of people with metastatic breast cancer,” said Sonya Negley, Executive Director, Metavivor. “We are thrilled to see the approval of Orserdu, a new oral endocrine therapy, for patients who have tumors that harbor ESR1 mutations, which are present in up to 40% of ER+, HER2- advanced or metastatic breast cancer. We advise patients to get tested for ESR1 mutations at progression in their metastatic treatment, so that their healthcare team can identify the right treatment options for their disease.“

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

FDA Approves Orserdu (elacestrant) for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer