As previously communicated, the combination of V940 (mRNA-4157) along with KEYTRUDA is currently under investigation in INTerpath-001, formerly known as V940-001. This is a global Phase III trial involving approximately 1,089 patients with resected high-risk (Stage IIB-IV) melanoma. The trial, which is double-blind and includes both placebo and active comparators, is actively screening participants in 14 countries: Australia, Belgium, Canada, Chile, France, Germany, Greece, Israel, Italy, Poland, Portugal, Spain, Turkey, and the United Kingdom. Currently, there are 38 sites participating in this study. The companies have plans to further expand the comprehensive clinical development program for V940 (mRNA-4157) to include additional tumor types.
FDA Approves Vertex and CRISPR Therapeutics’ CASGEVY for the Treatment of Sickle Cell Disease
Vertex Pharmaceuticals Incorporated and CRISPR Therapeutics have received the green light from the U.S. Food and Drug Administration (FDA) for CASGEVY, a cutting-edge CRISPR/Cas9 genome-edited cell therapy designed for the treatment of sickle cell disease (SCD) in patients aged 12 and older experiencing recurrent vaso-occlusive crises (VOCs). This significant approval signals a transformative approach, offering a durable one-time therapy with the potential for a functional cure. Approximately 16,000 SCD patients may now be eligible to benefit from a treatment that aims to eliminate severe VOCs and the associated hospitalizations.
Dr. Reshma Kewalramani, CEO and President of Vertex, highlighted the historic achievement of CASGEVY receiving FDA approval. As the first CRISPR-based gene-editing therapy in the U.S., CASGEVY represents a groundbreaking advancement, providing a one-time transformative therapy for eligible sickle cell disease patients. Dr. Kewalramani expressed profound gratitude to the patients and investigators whose trust propelled the program to this significant milestone.
“From the outset, our company’s vision was to apply CRISPR technology to revolutionize therapeutic approaches. Witnessing the U.S. approval of the first-ever CRISPR gene-edited medicine is nothing short of breathtaking. This is a profoundly humbling moment for me and for our entire organization,” shared Dr. Samarth Kulkarni, Chairman and CEO of CRISPR Therapeutics.
CASGEVY, with its nuanced requirements in stem cell transplantation, demands a high level of specialized experience. Vertex is actively working with experienced hospitals to build a network of independently operated authorized treatment centers (ATCs) across the U.S., ensuring widespread accessibility for patients.
Solid Biosciences Receives FDA Fast Track Designation for Duchenne Muscular Dystrophy Gene Therapy SGT-003
Solid Biosciences Inc. (Nasdaq: SLDB) disclosed on December 7, 2023, that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for SGT-003, the company’s advanced gene therapy candidate for Duchenne Muscular Dystrophy (Duchenne).
SGT-003 uses a proprietary, rationally designed capsid (AAV-SLB101) to deliver a DNA sequence encoding a shortened form of the dystrophin protein (microdystrophin), containing the R16-R17 nNOS binding domain. Preclinical data suggests this may be important for both muscular function and durability of benefit in patients.
Earlier, in November 2023, the FDA cleared SGT-003 for Investigational New Drug (IND) status. The upcoming Phase 1/2 trial, SGT-003-101, represents a pioneering, open-label, multicenter study aimed at assessing the safety and tolerability of SGT-003 in pediatric DMD patients at a dose of 1E14vg/kg. Administered as a single intravenous infusion, SGT-003 will be given to patients in two cohorts, each with a minimum of three patients, and the potential for expanding these cohorts. Cohort 1 will focus on patients aged 4 to < 6 years with DMD. The study plans to evaluate the treatment’s long-term safety and effectiveness over a period of 5 years post-treatment.
Receipt of FDA Fast Track Designation underscores the importance of rapidly developing SGT-003 to potentially aid the unmet needs of the Duchenne community,” said Bo Cumbo, President and CEO at Solid Biosciences. “Having received IND clearance for SGT-003 last month, we are pleased to be expediting the development of a potentially life-changing therapy and look forward to continuing to work closely with the FDA.
We appreciate the FDA’s partnership and their recognition of the continuing unmet need in the DMD community,” said Jessie Hanrahan, Ph.D., Chief Regulatory Officer at Solid Biosciences. “We look forward to frequent engagements with the Agency to discuss development of SGT-003 and ensure that our clinical development program will appropriately collect the data needed to support review of SGT-003 for future marketing authorization.
Duchenne Muscular Dystrophy is a genetic condition causing muscle degeneration primarily in boys, typically displaying symptoms between ages three and five. It is a progressive, incurable, and ultimately lethal disorder, impacting roughly one in every 3,500 to 5,000 live male births. As per DelveInsight, the Duchenne Muscular Dystrophy (DMD) prevalent population in the 7MM was found to be 30,000+ in 2020. Epidemiology assessed for DMD showed that the US, in 2020, accounted for approximately 16,000+ prevalent cases of DMD. In the United States, in 2020, the highest proportion of age-specific cases were observed in 5–9 years, followed by age groups of 10–14 years and 15–20 years. Similarly, among the EU-5 countries in 2020, the UK had the highest prevalent population of DMD patients with 2,600+ cases, followed by Germany and France. In contrast, Spain had the lowest cases in 2020. Globally, several pharma companies including Solid Biosciences, among others are addressing Duchenne Muscular Dystrophy treatment challenges through innovative gene therapies and targeted approaches aimed at improving patients’ quality of life.
bluebird bio Announces FDA Approval of LYFGENIA™ (lovotibeglogene autotemcel) for Patients Ages 12 and Older with Sickle Cell Disease and a History of Vaso-Occlusive Events
bluebird bio (Nasdaq: BLUE) shared on December 8, 2023, that the U.S. Food and Drug Administration (FDA) had approved LYFGENIA™ (pronounced as ‘lif-JEN-ee-uh’), also called lovo-cel. This approval pertains to its use in treating Sickle Cell Disease among patients aged 12 and above who have a history of vaso-occlusive events (VOEs). LYFGENIA, a one-time gene therapy, aims to address the root cause of Sickle Cell Disease and potentially resolve vaso-occlusive events. The FDA approval of LYFGENIA builds on decades of research into lentiviral vector gene addition therapy and the largest clinical development program of any gene therapy for Sickle Cell Disease. The label is based on data from patients from the Phase 1/2 HGB-206 study.
Safety data utilized for the application encompasses information from 54 patients who commenced stem cell collection. LYFGENIA’s efficacy was validated using data from 36 patients in the Phase 1/2 HGB-206 Group C study, reflecting refinements made to the treatment and manufacturing processes throughout the clinical development. Among these, 32 patients were assessed for achieving complete resolution of vaso-occlusive events (VOEs) and severe VOEs in the 6-18 months post-infusion, including 8 adolescent patients.
LYFGENIA operates by integrating a functional β-globin gene into the hematopoietic (blood) stem cells (HSCs) of patients, providing a permanent effect. Successful engraftment anticipates the sustained generation of adult hemoglobin featuring anti-sickling properties (HbAT87Q). This variant of hemoglobin, HbAT87Q, mirrors the oxygen-binding affinity of natural HbA, curbing the deformation of red blood cells and holding promise in diminishing vaso-occlusive events (VOEs).
The Phase 1/2 trial, HGB-206, for LYFGENIA is currently in progress, having finished enrollment and treatment. Simultaneously, the Phase 3 trial, HGB-210, examining LYFGENIA, is ongoing. Additionally, bluebird bio is conducting a follow-up study, LTF-307, focusing on the long-term safety and effectiveness of LYFGENIA in patients with Sickle Cell Disease who participated in bluebird bio-sponsored clinical studies.
Bringing LYFGENIA to people living with Sickle Cell Disease is a milestone that bluebird has been working toward for almost a decade—and one that members of the Sickle Cell Disease community have been waiting on for much longer,” said Andrew Obenshain, chief executive officer, bluebird bio. “LYFGENIA has the potential to have a transformational impact for patients who currently live under the shadow of unpredictable and debilitating vaso-occlusive events. This approval also marks bluebird’s third ex vivo gene therapy approved by the FDA for a rare genetic disease and second FDA approval for an inherited hemoglobin disorder, cementing our position as a gene therapy leader.
People living with Sickle Cell Disease face potentially devastating health consequences, diminished quality of life, and harmful stigma as a result of their disease,” said Julie Kanter, M.D., a LYFGENIA investigator and director of the University of Alabama Birmingham Adult Sickle Cell Clinic and associate professor in the Division of Hematology and Oncology. “Today we can celebrate the availability of a potentially transformative new therapeutic option made possible by the incredible courage of patients and families who participated in clinical studies.
In June 2023, LYFGENIA obtained Priority Review status. Despite this, the Company did not receive a Rare Pediatric Disease Priority Review Voucher during the review process. LYFGENIA had previously been designated as an orphan drug, received fast track designation, regenerative medicine advanced therapy (RMAT) designation, and was also designated as a rare pediatric disease treatment.
Sickle Cell Disease, a multifaceted and advancing genetic condition, is linked to unexpected and incapacitating vaso-occlusive events (VOEs). Within this disease, elevated levels of sickle hemoglobin (HbS) in red blood cells (RBCs) result in their deformation, adhesiveness, and inflexibility, leading to a shorter lifespan. This condition acutely presents as hemolytic anemia, vasculopathy, and vaso-occlusion. The impact of VOEs is all-encompassing and can disrupt various aspects of life for both patients and their families or caregivers.
Ipsen Confirms US FDA Grants Priority Review For New Drug Application for Elafibranor for the Treatment of Primary Biliary Cholangitis
Ipsen (Euronext: IPN; ADR: IPSEY) and GENFIT (Nasdaq and Euronext: GNFT) disclosed on December 7, 2023, that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for investigational elafibranor. This oral, once-daily dual peroxisome-activated receptor alpha/delta (PPAR α,δ) agonist holds promise as a potential groundbreaking second-line treatment for the rare cholestatic liver disease, PBC, marking a significant development after almost a decade without new therapies. The FDA has set the target PDUFA date for priority review on June 10, 2024.
ELATIVE, identified as a Phase III clinical trial (NCT04526665), is a multicenter study employing randomization, double-blinding, and placebo control. This trial aims to assess the efficacy and safety of elafibranor 80mg taken once daily as compared to a placebo for patients dealing with PBC, specifically those with an inadequate response to or intolerance of UDCA. With 161 enrolled patients, the trial allocated participants in a 2:1 ratio, receiving either elafibranor 80mg once daily or a placebo. Patients with an insufficient response to UDCA would continue receiving a combination of UDCA and elafibranor or placebo, while those unable to tolerate UDCA would solely receive elafibranor or placebo. Findings indicate elafibranor’s potential as a promising PBC treatment option, displaying a significant improvement in disease progression, as reflected by a biochemical response.
We are delighted to have achieved simultaneous filings for elafibranor, which is in line with our ambition to be able to bring a new and much needed medicine to as many people living with PBC as rapidly as possible,” said Christelle Huguet, EVP and Head of Research & Development, Ipsen. “This is a condition where many patients are living with worsening disease and debilitating symptoms despite being on treatment. Elafibranor, if approved, has the potential to change the management of this challenging condition for people living with PBC, offering a new second line treatment choice, where the number of effective options are currently limited.
These simultaneous regulatory submission acceptances are another important step in the elafibranor journey. We are pleased to be partnering with Ipsen, who we know has a good understanding of the rare-disease regulatory process,” said Pascal Prigent, Chief Executive Officer of GENFIT. “We know they share the same goal as GENFIT, to bring a new, much needed treatment option to people living with PBC as fast as possible; we look forward to elafibranor’s progress through the regulatory review processes.
The European Medicines Agency (EMA) has validated Ipsen’s Marketing Authorization Application (MAA) for elafibranor, initiating the review process by the EMA’s Committee for Medicinal Products for Human Use (CHMP) on October 26, 2023. Additionally, elafibranor has undergone a third concurrent regulatory submission, which has been validated for review by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). Earlier in 2019, the U.S. Food and Drug Administration granted elafibranor Breakthrough Therapy Designation for adults with PBC who don’t adequately respond to ursodeoxycholic acid (UDCA), the existing primary therapy. It’s important to note that elafibranor hasn’t yet received approval from regulatory authorities worldwide.
Primary Biliary Cholangitis (PBC) is a rare and autoimmune liver disease characterized by the gradual destruction of bile ducts within the liver. This damage hampers the liver’s capacity to eliminate toxins and may result in the formation of liver tissue scarring, recognized as cirrhosis. Notably, PBC predominantly affects women, with nine women diagnosed for every man. In 2022, the total Primary Biliary Cholangitis diagnosed prevalent cases was nearly 291,400+ in the 7MM. The highest number of cases was seen in the US, i.e., 139,400+ cases in 2022. Among the 7MM, Japan ranked second with around 44,400+ diagnosed prevalent cases of PBC in 2022, which is expected to increase by 2032. Among EU4 and the UK, Germany had the highest number of diagnosed prevalent cases of PBC with around 32,900+ cases in 2022. On the other hand, Spain had the lowest number of diagnosed prevalent cases of PBC, with about 10,000+ cases.
Unfortunately, a significant portion of individuals living with PBC don’t find relief from existing treatments available. If left untreated, PBC can progress to liver failure, and in some instances, prove fatal. However, several major pharma and biotech giants, such as Ipsen, among others, are actively working in the Primary Biliary Cholangitis therapeutics market.
