The FDA approval is based on the findings of the DINAMO phase III trial, which found Jardiance to be linked with a statistically significant reduction in the primary endpoint of change from baseline in A1c at 26 weeks compared to placebo in type 2 diabetes participants aged 10-17 years. Jardiance 10 mg and 25 mg pooled dosages lowered A1c by 0.8% compared to placebo at week 26 (95% CI 1.5 to 0.2; P=0.0116) when combined with additional baseline therapies (diet, exercise, metformin, and/or insulin). The safety profile of pediatric Jardiance patients was similar to that of adults with type 2 diabetes, with the exception of hypoglycemia risk, which was increased in pediatric Jardiance patients regardless of concomitant insulin administration.
FDA Approves Pfizer’s LITFULO for Adults and Adolescents With Severe Alopecia Areata
Pfizer Inc. announced that the US Food and Drug Administration (FDA) has approved LITFULO (ritlecitinib), a once-daily oral medication, for adults 12 years of age and older with severe alopecia areata. LITFULO has an established recommended dose of 50 mg. It is the first and only FDA-approved medication for adolescents (12 and older) with severe alopecia areata.
“While patients may develop symptoms of alopecia areata at any age, most people start showing signs in their teens, twenties, or thirties,” stated Dr. Brittany Craiglow, Associate Professor Adjunct – Dermatology at Yale School of Medicine. “LITFULO is a critical treatment option for younger patients with significant hair loss, who frequently struggle with such a visible disease.”
The FDA granted approval based on clinical trial results in alopecia areata. The efficacy and safety of LITFULO were studied at 118 sites in 18 countries in the ALLEGRO Phase IIb/III trial, which involved 718 patients with 50% or more scalp hair loss as defined by the Severity of Alopecia Tool (SALT). After six months, 23% of patients treated with LITFULO 50 mg had 80% or more scalp hair covering (SALT20), compared to 1.6% of patients treated with placebo. LITFULO’s efficacy and safety were consistent in teenagers (12 to 17 years old) and adults (18 years and older).
“People suffering from alopecia areata are commonly misunderstood, and their experience is typically dismissed as ‘just hair.’ “It is, however, a serious autoimmune disease with significant negative consequences beyond the physical symptoms,” stated Nicole Friedland, President and Chief Executive Officer of the National Alopecia Areata Foundation (NAAF). “We believe that the approval of LITFULO is a significant step forward in the treatment of alopecia areata, particularly in adolescents.” It’s encouraging to see additional FDA-approved therapies become available to this population.”
Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy
Sarepta Therapeutics declared U.S. Food and Drug Administration accelerated approval of ELEVIDYS, adeno-associated virus-based gene therapy for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy with a confirmed mutation in the DMD gene. This indication is approved under accelerated approval based on the expression of ELEVIDYS micro-dystrophin observed in patients treated with ELEVIDYS. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial(s). ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.
ELEVIDYS is designed to tackle the underlying genetic cause of Duchenne muscular dystrophy, which involves mutations in the dystrophin gene resulting in a deficiency of dystrophin protein. It achieves this by introducing a modified form of the dystrophin gene, called ELEVIDYS micro-dystrophin, into muscle cells. The recent approval of ELEVIDYS was expedited due to an observed rise in the expression of ELEVIDYS micro-dystrophin protein in skeletal muscles. The approval was supported by both biological and empirical evidence, as well as efficacy data from two clinical studies (SRP-9001-102 and SRP-9001-103) and safety data from three studies (SRP-9001-101, SRP-9001-102, and SRP-9001-103).
However, it is important to note that the use of ELEVIDYS has been associated with certain risks. Patients treated with ELEVIDYS have experienced serious liver injury, immune-mediated myositis, and myocarditis. The most common adverse reactions observed in clinical studies include vomiting, nausea, elevated liver function test results, fever, and low platelet count.
To comply with the requirements of the accelerated approval pathway, the company has committed to conducting a confirmatory trial. The trial, called EMBARK, is a global, randomized, double-blind, placebo-controlled Phase 3 study for ELEVIDYS. Enrollment for the trial has been completed, and the top-line results are anticipated to be available by late 2023. EMBARK will serve as a post-marketing confirmatory trial.
Dr. Jerry Mendell, a pediatric neurologist and principal investigator at the Center for Gene Therapy in Nationwide Children’s Hospital, emphasized the debilitating nature of Duchenne muscular dystrophy, which progressively weakens muscles and affects children. He expressed optimism about the potential impact of ELEVIDYS, highlighting the increased expression of dystrophin and the functional improvements observed in patients, which could significantly improve their quality of life.
“The approval of ELEVIDYS represents a significant milestone in the treatment of Duchenne muscular dystrophy,” stated Doug Ingram, the President and CEO of Sarepta. He emphasized that ELEVIDYS is the first and only gene therapy to receive approval for Duchenne, bringing them closer to their goal of offering a treatment that has the potential to change the course of this degenerative disease. Ingram expressed gratitude towards the patient community, families, clinicians, and Sarepta colleagues for their years of dedication and effort, which culminated in the approval of ELEVIDYS. He also mentioned the ongoing confirmatory trial, EMBARK, with top-line results expected later this year. If EMBARK confirms the positive outcomes observed in previous trials, Sarepta intends to promptly submit a BLA (Biologics License Application) supplement to expand the approved indications based on sound scientific evidence.
Pat Furlong, the Founding President and CEO of Parent Project Muscular Dystrophy, described the approval as a significant moment in gene therapy for individuals living with Duchenne. She acknowledged the lifelong work of many individuals within the Duchenne community and emphasized the continued efforts to ensure that all patients in the community have access to this therapy.
Tonix Pharmaceuticals to Acquire Two FDA-Approved, Marketed Migraine Products from Upsher-Smith Laboratories
Tonix Pharmaceuticals and its wholly-owned subsidiary Tonix Medicines a clinical-stage biopharmaceutical company, today announced that they have agreed to acquire two currently-marketed products from Upsher-Smith Laboratories (Upsher-Smith): Zembrace® SymTouch® (sumatriptan injection) 3 mg and Tosymra® (sumatriptan nasal spray) 10 mg. Zembrace SymTouch and Tosymra are both indicated for the treatment of acute migraine with or without aura in adults. Zembrace SymTouch is the sole branded autoinjector of sumatriptan that is actively promoted for professional use in the United States. It is specifically designed to be user-friendly and well-tolerated, offering a low dose of 3 mg.
On the other hand, Tosymra is an innovative intranasal sumatriptan product that incorporates a permeation enhancer, enabling rapid and efficient absorption of sumatriptan. These products collectively generated approximately $23 million in sales throughout the entirety of 2022. Both Zembrace SymTouch and Tosymra have the potential to provide relief from migraine pain within just 10 minutes for certain patients. Importantly, Zembrace SymTouch is protected by a patent until 2036, while Tosymra enjoys patent protection until 2031.
Under the terms of the agreement with Upsher-Smith:
- paraphrase: Tonix Medicines will make an upfront payment of $12 million in cash to Upsher-Smith at closing and an additional $3 million in March 2024, or upon earlier conclusion of the transition services period.
- In addition, Tonix Medicines will pay approximately $10 million in cash to Upsher-Smith at closing to acquire certain product-related inventories.
- To support the transition of the products, Upsher-Smith has agreed to provide certain commercial operations, regulatory, and other transition services to Tonix Medicines for up to nine months after closing, in exchange for agreed-upon service fees.
- The assets to be acquired include New Drug Applications issued by the U.S. Food & Drug Administration for the products, as well as patents and trademarks related to the products in the United States and certain countries outside the United States.
- The closing is expected to take place on June 30, 2023.
Tosymra, a sumatriptan nasal spray, employs Intravail® permeation enhancer technology and is equivalent in pharmacokinetics to a subcutaneous sumatriptan dose of 4 mg. It has demonstrated the potential to provide migraine pain relief in as little as 10 minutes with a single spray for certain patients (13% compared to 5% with a placebo). Tosymra is also covered by patents until 2031.
FDA Grants Orphan Drug Designation to ERAS-801 for Malignant Glioma
The FDA has designated ERAS-801 as an orphan drug for the treatment of malignant gliomas, including glioblastoma (GBM), according to a statement from Erasca, Inc. (Nasdaq: ERAS). In preclinical animal investigations, the orally accessible, small-molecule EGFR inhibitor ERAS-801 exhibited substantial central nervous system (CNS) penetration in preclinical animal studies.
“Receiving ODD recognizes both the importance of innovation for patients with Glioblastoma and the therapeutic potential of ERAS-801 to provide a targeted treatment option for these patients, who have a poor prognosis. This ODD follows the earlier Fast Track Designation granted to ERAS-801 by the FDA and underscores the urgency of finding new treatments for this patient population. The broad activity against both oncogenic and wildtype EGFR, high CNS penetration, and demonstrated ability to improve outcomes in over 90% of diverse EGFR-driven patient-derived glioma models support the potential for ERAS-801 to overcome current challenges with existing therapies. We anticipate reporting initial monotherapy data for ERAS-801 from the Phase 1 THUNDERBBOLT-1 trial in patients with recurrent Glioblastoma in the second half of 2023.”
Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and Co-founder
ERAS-801 is a highly potent, selective, reversible, and orally bioavailable small molecule EGFR inhibitor. It also has significantly enhanced CNS penetration. ERAS-801’s brain-to-plasma partition coefficient (Kp) in animal models was 3.7 and its unbound partition coefficient (Kp,uu) was 1.2, both of which were up to four times higher than those of approved EGFR inhibitors, suggesting that approximately 100% of the free drug in plasma is able to cross the blood-brain barrier (BBB).
At clinically relevant exposures across 30 patient-derived Glioblastoma models that were intended to represent the heterogeneity of GBM, ERAS-801 demonstrated a survival benefit in 13 out of 14 (93%) EGFR mutant and/or amplified models and had statistically significantly higher brain penetrance and prolonged survival compared to approved EGFR tyrosine kinase inhibitors, including osimertinib, lapatinib, and erlotinib. In the ongoing Phase 1 trial THUNDERBBOLT-1, which is being conducted in patients with recurrent Glioblastoma (rGBM), ERAS-801 is being assessed as a monotherapy.
ERAS-801 is being tested in THUNDERBBOLT-1 to evaluate the safety, tolerability, and preliminary efficacy of the drug as a monotherapy for people with rGBM. The suggested dose will be established during the dose escalation phase and used during the dose-expansion phase to further assess the effectiveness and safety of ERAS-801. Future THUNDERBBOLT-1 substudies might investigate ERAS-801 in combination with different medications and in a wider range of patient populations. In the second part of 2023, the first Phase 1 results from Thunderbolt-1 are anticipated. In June 2023, the FDA granted ODD to ERAS-801 for the malignant glioma treatment, which includes glioblastoma. Earlier, in April 2023, the FDA granted Fast Track Designation (FTD) to ERAS-801 for the treatment of adult patients with Glioblastoma with EGFR gene alterations.
As per DelveInsight, the total diagnosed incident population of Glioblastoma in the 7MM was 32,546 cases in 2021 and are projected to increase in the coming years. Among the EU-4, the UK countries, Germany accounted for the highest number of Glioblastoma cases, followed by France, whereas Spain accounted for the lowest number of cases in 2021. The ongoing clinical and commercial activities in the Glioblastoma therapeutics market, anticipated a better treatment outcome in the coming years.
FibroGen Announces Topline Results from Phase 3 ZEPHYRUS-1 Study of Pamrevlumab for IPF the Treatment
On June 26, 2023, FibroGen, Inc. (NASDAQ: FGEN) announced topline results from its Phase 3 ZEPHYRUS-1 trial evaluating the safety and efficacy of pamrevlumab in patients with Idiopathic Pulmonary Fibrosis (IPF). The study compared treatment with pamrevlumab to placebo and did not meet the primary endpoint of change from baseline in forced vital capacity (FVC) at week 48 (p=0.29). The mean decline in FVC from baseline to week 48 was 260 ml in the pamrevlumab arm compared to 330 ml in the placebo arm (placebo-corrected difference of 70 ml; 95% CI -60 to 190 ml). The secondary endpoint of time to disease progression (FVC percent predicted decline of ≥10% or death) was also not met (HR= 0.78; 95% CI 0.52 to 1.15).
We are deeply disappointed that these results do not support pamrevlumab as a new treatment for IPF. FibroGen would like to thank the patients and clinical trial investigators for their dedication to participating in this study.
Mark D. Eisner, MD, MPH, Chief Medical Officer, FibroGen
FibroGen’s focus will be on reporting the additional pamrevlumab studies, advancing our pipeline, and continuing commercialization of roxadustat in China and in countries where approved.
Enrique Conterno, Chief Executive Officer, FibroGen.
ZEPHYRUS-1 is a randomized, double-blind, placebo-controlled, multi-center Phase 3 trial aimed at assessing the effectiveness and safety of pamrevlumab in individuals with Idiopathic Pulmonary Fibrosis. A total of 356 patients with IPF were enrolled in ZEPHYRUS-1. For 48 weeks, patients were randomly assigned (1:1) to either pamrevlumab or a placebo. Two studies, ZEPHYRUS-1 and ZEPHYRUS-2, make up the Phase 3 clinical research programme assessing pamrevlumab for the treatment of IPF. These trials are multi-center, randomised, double-blind, placebo-controlled Phase 3 studies intended to assess the effectiveness and safety of pamrevlumab in IPF patients.
In the safety analysis, pamrevlumab was generally safe and well tolerated, and the majority of treatment-emergent adverse events were mild or moderate. Treatment-emergent serious adverse events were observed in 28.2% of patients in the pamrevlumab group and 34.3% of patients in the placebo group.
Topline results from pamrevlumab Phase 3 studies for the treatment of ambulatory DMD patients (LELANTOS-2), locally advanced pancreatic cancer patients (LAPIS), and metastatic pancreatic cancer patients (Precision Promise) are expected to be released by FibroGen in 3Q 2023, 1H 2024, and 3Q 2025, respectively. Based on the results of ZEPHYRUS-1, ZEPHYRUS-2, the second Phase 3 clinical trial, will be discontinued. FibroGen plans to communicate the results of the ZEPHYRUS-1 study at an upcoming medical forum.
As per DelveInsight, the total diagnosed prevalent cases of Idiopathic Pulmonary Fibrosis in the 7MM was 194,000+ cases in 2021 which is expected to rise, at a CAGR of 1.1% during the study period (2019–2032). The highest diagnosed prevalent cases of Idiopathic Pulmonary Fibrosis were accounted for by the US in 2021, with 94,000+ cases in the 7MM, which is expected to show a steep rise soon due to the improvement in diagnostic testing and increasing population. Moreover, among the European countries, Germany had the highest diagnosed prevalent population of IPF with 20,000+ cases, followed by the UK in 2021. On the other hand, Spain had the lowest diagnosed prevalent population. To overcome the existing burden of unmet need for better outcomes, several major pharma and biotech companies are actively working in the Idiopathic Pulmonary Fibrosis therapeutics market. The ongoing clinical and therapeutics activities hold significant potential to immensely improve the treatment scenario in the upcoming years.
