Sarepta Therapeutics Announces Positive Vote from U.S. FDA Advisory Committee Meeting for SRP-9001 Gene Therapy

Sarepta Therapeutics, Inc., a pioneer in precision genetic medicine for rare diseases, announced that the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 8 to 6 in favor of accelerated approval of SRP-9001 (delandistrogene moxeparvovec) for the treatment of ambulatory patients with Duchenne muscular dystrophy who have a confirmed mutation in the DMD gene.

“Today’s advisory committee outcome is extremely important to the patient community, who are in desperate need of new therapies,” said Doug Ingram, Sarepta’s president and CEO. “We will work collaboratively with the FDA to complete the review of our BLA for SRP 9001, with the May 29 action date as our top priority.” We sincerely thank the families, clinicians, FDA presenters, and committee members who participated in today’s panel, as well as everyone who contributed feedback and comments in both the written record and the open public hearing.”

SRP-9001 is intended to treat the underlying cause of Duchenne muscular dystrophy, which is characterized by mutations in the dystrophin gene that result in a lack of dystrophin protein. Muscles become weakened and injured in the absence of dystrophin, which is essential for muscular strengthening and protection. SRP-9001 is designed to deliver a gene that codes for a truncated, functional form of dystrophin to muscle cells. The committee’s favorable vote is based on an assessment of all evidence, including the SRP-9001 product design as well as biological and empirical data. SRP-9001 is backed by non-clinical evidence as well as efficacy and safety data from trials 101, 102, and 103, as well as an integrated analysis of these three clinical investigations comparing functional results to a propensity-score-weighted external control (EC).

The CTGTAC’s vote, while not binding, will be taken into account by the FDA when making its judgment on SRP-9001’s prospective fast approval. The FDA is now reviewing the Biologics Licence Application (BLA) for SRP-9001, with a regulatory action deadline of May 29, 2023.

FDA Approves Astellas’ VEOZAH for Vasomotor Symptoms Due to Menopause

Astellas Pharma Inc. announced that the U.S. Food and Drug Administration (FDA) approved VEOZAH (fezolinetant) 45 mg once daily for the treatment of moderate to severe vasomotor symptoms (VMS) caused to menopause. VEOZAH is the first nonhormonal neurokinin 3 (NK3) receptor antagonist licensed to treat VMS caused by menopause.

VMS, which is characterized by hot flashes and/or night sweats, is a frequent menopausal symptom. VMS is the most prevalent menopausal symptom for which women seek vasomotor symptoms treatment. In the United States, approximately 60% to 80% of women have these symptoms during or after menopause. VMS can interfere with women’s daily activities and general quality of life.

“Today’s approval of fezolinetant is a significant and, I believe, a long-awaited milestone for individuals in the United States who experience moderate to severe vasomotor symptoms during the menopausal transition,” said Genevieve Neal-Perry, M.D., Ph.D., Chair of the Department of Obstetrics and Gynaecology at the UNC School of Medicine. “This therapy is based on our knowledge of the biology of hot flashes.” I’m thrilled that patients will be able to choose this nonhormonal treatment.”

The approval is based on the results of the BRIGHT SKY program, which included three Phase III clinical trials as part of a development program that involved over 3,000 people in the United States, Canada, and Europe. The results of the pivotal trials SKYLIGHT 1 and SKYLIGHT 2 characterize the efficacy and safety of fezolinetant for the treatment of moderate to severe VMS due to menopause. Data from the SKYLIGHT 4 safety research help to characterize fezolinetant’s long-term safety profile.

Fezolinetant marketing authorization applications are also being reviewed by regulators in the EU, Switzerland, and Australia. The impact of this decision has already been factored into Astellas’ financial forecast for the current fiscal year, which ends on March 31, 2024.

FDA Grants SiSaf’s Innovative siRNA Therapy SIS-101-ADO Orphan Drug Designation and Rare Pediatric Disease Designation

SiSaf Ltd has received Orphan Drug Designation from the U.S. FDA. Additionally, SIS-101-ADO has been granted Rare Pediatric Disease Designation for the treatment of Autosomal Dominant Osteopetrosis, a rare skeletal disorder with severe implications for children.

The Orphan Drug Designation by the FDA provides SiSaf with various benefits, including tax credits for clinical trials, exemption from user fees, and extended exclusivity in the marketplace. On the other hand, the Rare Pediatric Disease Designation allows SiSaf to apply for a priority review voucher, which expedites the drug approval process by the FDA.

The FDA granted SIS-101-ADO the Rare Pediatric Disease Designation due to the significant and life-threatening effects of Autosomal Dominant Osteopetrosis in children, including optic nerve compression leading to blindness, developmental anomalies in the teeth and skull, and scoliosis.

At present, there are no approved treatments or ongoing clinical trials for Osteopetrosis ADO2, making SiSaf’s SIS-101-ADO a potentially groundbreaking solution for this debilitating disease. If approved, it could significantly improve the lives of those affected. SiSaf is currently making preparations for initial human trials.

SIS-101-ADO combines SiSaf’s Bio-Courier delivery technology with an siRNA that targets and suppresses the expression of CLCN7. This mutant gene is responsible for ADO2 and is expressed by osteoclasts and other cell types. By reducing the expression of CLCN7, the RNA therapy can restore bone mass and quality to nearly normal levels.

Genetic skeletal disorders like ADO2 contribute to around five percent of all global birth defects. However, there are still significant unmet needs and challenges in providing safe and effective treatments. SiSaf’s proprietary Bio-Courier technology has the potential to accelerate the development of new RNA-based treatments. Unlike other RNA delivery technologies, SiSaf’s technology addresses limitations by using bioabsorbable silicon to stabilize lipid nanoparticles.

According to Dr. Suzanne Saffie-Siebert, the Founder and CEO of SiSaf, the granting of Orphan Drug Designation and Rare Pediatric Disease Designation represents a significant milestone in their mission to advance their groundbreaking siRNA treatment for the relief of pain and suffering caused by Osteopetrosis ADO2. Dr. Saffie-Siebert believes that SIS-101-ADO has the potential to usher in a new era of personalized care and treatment options not only for ADO2 but also for other rare bone and skeletal diseases.

RNA therapeutics have gained considerable attention as a potential solution for various medical conditions, and SiSaf’s innovative Bio-Courier delivery technology for siRNA shows promise in addressing even the most challenging diseases.

Dr. Saffie-Siebert further mentioned that SIS-101-ADO, along with other drugs formulated using Bio-Courier, will not only have the ability to treat rare skeletal disorders but also pave the way for therapeutics targeting other rare diseases that were previously considered untreatable.

FDA Grants Fast Track Designation to IMPT-314 for Relapsed/Refractory B-cell Lymphoma

ImmPACT Bio USA has announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to IMPT-314, a potential groundbreaking therapy utilizing CD19/CD20 CAR T cells. It aims to treat patients with B-cell mediated malignancies, including aggressive B-cell lymphoma that has relapsed or is refractory, diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), and DLBCL that originated from follicular lymphoma (FL) after two or more lines of systemic therapy.

IMPT-314 is the result of research conducted by Yvonne Chen, Ph.D., who is an associate professor at the University of California, Los Angeles (UCLA). In 2019, Sarah Larson, M.D., also from UCLA, initiated an ongoing Phase 1 study of IMPT-314 in patients with relapsed or refractory non-Hodgkin lymphoma. ImmPACT Bio obtained the logic-gate-based CAR T-cell platforms from UCLA through a licensing agreement.

Significant findings from the Phase 1 investigator-led study conducted at UCLA, involving 11 participants, include the following key safety and efficacy results:

  • A remarkable objective response rate of 91%, with 73% of patients achieving a durable complete response.
  • A median progression-free survival of 18.2 months, based on a median follow-up of 20.5 months.
  • No cases of neurotoxicity or immune effector cell-associated neurotoxicity syndrome were reported.
  • There were no instances of cytokine release syndrome above Grade 1.

Fast Track Designation (FTD) aims to expedite the development and review of drugs that address unmet medical needs or treat serious and life-threatening conditions. This designation enables closer and more frequent collaboration between ImmPACT Bio and the FDA during the clinical development process. If certain criteria are met, the FDA may even consider reviewing portions of a marketing application before the complete submission.

ImmPACT Bio plans to assess the effectiveness of IMPT-314 in a Phase 1/2 clinical trial focused on aggressive B-cell lymphoma, including DLBCL. The dosing of the first patient is anticipated to occur in the second quarter of 2023, with preliminary safety and efficacy data expected to be available in the latter half of the same year.

FDA Approves First Drug for Agitation in People With Alzheimer’s Disease

On May 10, 2023, Otsuka Pharmaceutical, Co. Ltd. (Otsuka) and Lundbeck LLC (Lundbeck) announce the US FDA has approved the supplemental New Drug Application (sNDA) of REXULTI® (brexpiprazole) for use in the treatment of agitation associated with dementia due to Alzheimer’s disease. With this approval, REXULTI becomes the first and only pharmacological treatment approved in the US for agitation associated with dementia due to Alzheimer’s disease. 

The submission was based on two Phase 3, 12-week, randomized, double-blind, placebo-controlled fixed-dose studies that evaluated the frequency of agitation symptoms in patients with dementia due to Alzheimer’s disease based on the Cohen-Mansfield Agitation Inventory (CMAI) total score. As per the update, Brexpiprazole patients with agitation associated with dementia due to Alzheimer’s disease achieved a 31% greater reduction from baseline in the frequency of agitation symptoms vs. placebo.

Brexpiprazole was discovered by Otsuka and is being co-developed by Otsuka and Lundbeck.  The mechanism of action of brexpiprazole is unknown, however, the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors.

“Today marks a major milestone for patients, caregivers, and families navigating the complexities of agitation associated with dementia due to Alzheimer’s disease. Otsuka Pharmaceutical will continue its efforts to engage and provide options for those impacted by this devastating condition.”

Makoto Inoue, president and representative director of Otsuka

“This approval is a testament to our commitment and unwavering support of patients and caregivers to lessen the symptoms of agitation associated with dementia due to Alzheimer’s disease. We look forward to offering this first FDA-approved treatment option to address this significant unmet need for patients. We are grateful to the patients and caregivers who participated in these important trials.”

Deborah Dunsire, CEO and president, Lundbeck

Agitation is a common neuropsychiatric symptom associated with Alzheimer’s dementia, and it is also one of the most complex and stressful aspects of caring for people living with the condition. About half of all patients with Alzheimer’s dementia report having agitation, a typical neuropsychiatric symptom associated with dementia brought on by Alzheimer’s disease. The illness has a significant influence on the patients’, their families’, and carers’ quality of life. Agitation associated with dementia covers a large group of behaviors occurring in patients with Alzheimer’s disease, such as pacing, gesturing, profanity, shouting, shoving, and hitting. 

CytoAgents Announces FDA Acceptance of IND Application for CTO1681 to Treat Cytokine Release Syndrome in Oncology

On May 11, 2023, CytoAgents announced that it has received a Study May Proceed letter from the US FDA. With this approval, it has enabled CytoAgents to initiate of a U.S. Phase 1b/2a clinical trial under its Investigational New Drug (IND) application for the therapeutic, CTO1681, to treat Cytokine Release Syndrome in lymphoma patients receiving CAR T-Cell Therapy. It is observed that there has a great unmet medical need, as the majority of patients undergoing CAR T treatment for their cancer experience Cytokine Release Syndrome and associated neurotoxicity. CytoAgents anticipates the clinical trial to launch at its first trial site in the summer of 2023.

“We are thrilled to advance CTO1681 into the clinic and excited about how our novel therapeutic will potentially prevent and treat CRS. The FDA’s clearance to advance our clinical program for CTO1681 in the U.S. is another important milestone for our company.”

Teresa Whalen, RPh, CEO of CytoAgents.

Moreover, CytoAgents has also revealed the initial closing of its second equity financing round. Brian Shanahan, Managing Partner, PCG Capital, has said, “CytoAgents has a clear path forward and a team ready to execute. We are excited to support the acceleration of CytoAgents’ clinical development efforts and look forward to generating meaningful clinical data in patients.”

Commonly referred to as cytokine storm, Cytokine Release Syndrome is an acute systemic inflammatory response characterized by fever and multiple organ dysfunction associated with CAR T-cell therapy, therapeutic antibodies, haploidentical allogeneic transplantation, etc. Cytokine Release Syndrome is caused by excessive cytokine production and can be triggered by a range of diseases and treatments. Certain advanced immunotherapies in the oncology space such as CAR T-Cell and Bispecific Antibody Therapies suffer from high incidence of associated Cytokine Release Syndrome. Cytokine Release Syndrome’s complex signs and symptoms result from the effects of cytokines released by the CAR T cells once engaged with the target. 

Till now, only one therapy is approved for Cytokine Release Syndrome treatment, i.e., ACTEMRA (tocilizumab). Apart from this therapy, the treatment also depends on the use of off-labeled drugs. CytoAgents’ drug candidate, CTO1681 (formerly GP1681), prevents and treats Cytokine Release Syndrome by targeting the NF-kB signaling pathway and modulating cytokine production, resulting in reduced inflammation. NF-kB plays a critical role in the body’s natural regulation, activation, and differentiation of inflammatory T-cells.