FDA Approves ZURZUVAE, the First and Only Oral Treatment Approved for Women with Postpartum Depression

Biogen Inc. and Sage Therapeutics, Inc. announced that the FDA has approved ZURZUVAE (zuranolone) 50 mg for individuals with postpartum depression (PPD). ZURZUVAE is the first and only 14-day oral, once-daily therapy for women with PPD that can produce quick relief of depression symptoms. ZURZUVAE is projected to be commercially available in the fourth quarter of 2023, following its designation as a restricted substance by the United States Drug Enforcement Administration, which is likely to happen within 90 days.

Furthermore, the FDA granted a Complete Response Letter (CRL) for zuranolone’s New Drug Application (NDA) for the treatment of adults with major depressive disorder (MDD). The CRL said that the application did not present sufficient evidence of efficacy to support the approval of zuranolone for the treatment of MDD and that further research will be required. Biogen and Sage are studying the feedback and deciding what measures to take next.

The approval of ZURZUVAE to treat postpartum depression is a significant milestone for the hundreds of thousands of women who suffer from this underdiagnosed and undertreated condition,” said Biogen President and Chief Executive Officer Christopher A. Viehbacher. “We are grateful for the help of patients, patient advocates, and researchers in reaching this milestone.” We believe that ZURZUVAE will be an essential treatment option for PPD, and we will carefully evaluate the FDA’s feedback on the use of zuranolone in MDD to determine the next steps.

ZURZUVAE was approved for the treatment of PPD in women based on the NEST clinical development program, which included two trials in adult women with PPD (ROBIN and SKYLARK trials). Both studies achieved their primary goal of a significant mean reduction from baseline in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, a typical measure of depression severity, at Day 15 when compared to placebo. All critical secondary objectives were reached in the SKYLARK Study testing ZURZUVAE 50 mg, with significant reductions in depression symptoms noted as early as Day 3 and lasting until Day 45. 

Astellas Drug Acquired in $5.9B Deal Wins FDA Approval in Vision-Loss Disorder

On August 4, 2023, Astellas Pharma Inc. announced that the United States Food and Drug Administration (FDA) approved IZERVAY (avacincaptad pegol intravitreal solution) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). IZERVAY, a novel complement C5 inhibitor, is the only licensed geographic atrophy medication that has shown a statistically significant (p0.01) reduction in the rate of geographic atrophy progression at the 12-month primary endpoint in two Phase III clinical trials.

We are overjoyed to have received FDA approval for IZERVAY and to be able to offer a new therapy to physicians and appropriate patients in the United States. In this devastating progressive disease, time, vision, and safety all matter.” We’d want to thank everyone who helped us attain this milestone and keep our promise to pioneer revolutionary therapeutics for retinal illnesses.

Pravin U. Dugel, MD, President, Iveric Bio, An Astellas Company

Geographic atrophy affects an estimated 1.5 million persons in the United States. However, it is estimated that 75% of persons living with geographic atrophy in the United States are undiagnosed. Without prompt treatment, it is anticipated that 66% of patients with geographic atrophy will go blind or severely visually impaired.

The FDA granted approval based on the results of the GATHER1 and GATHER2 Phase III clinical trials, which assessed the safety and efficacy of monthly 2 mg intravitreal IZERVAY injection in individuals with geographic atrophy secondary to AMD. The rate of geographic atrophy increase was assessed at three points: baseline, six months, and twelve months. The primary analysis of each registrational trial over a 12-month period revealed a statistically significant reduction in the rate of geographic atrophy growth in patients treated with IZERVAY compared to sham. Disease progression was slowed as early as six months, with a 35% reduction in the first year of treatment.

FDA Grants Clearance for Phase III Study of Lisaftoclax in Previously Treated CLL/SLL

Ascentage Pharma, a worldwide biopharmaceutical company dedicated to developing innovative treatments for cancer, chronic hepatitis B, and age-related diseases, has announced that lisaftoclax (APG-2575), a novel Bcl-2 inhibitor and a crucial asset for the company, has received clearance from the US Food and Drug Administration (FDA) to enter a global Phase III study for the treatment of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma who were previously treated with a Bruton’s tyrosine kinase inhibitor (BTKi). This regulatory approval is a significant advancement in the global development of lisaftoclax and represents another essential milestone following its approval for a Phase II study in patients with relapsed/refractory CLL/SLL in China.

The upcoming global Phase III study (APG2575CG301) is designed to evaluate the effectiveness and safety of lisaftoclax (APG-2575) in combination with a BTKi in CLL/SLL patients who had received prior BTKi treatment. The study is scheduled to commence in the latter half of 2023.

CLL/SLL is the most prevalent form of leukemia in adults, accounting for a quarter of all leukemia cases in the Western World, with over 100,000 new diagnoses globally each year. Despite the initial responses to current first-line treatments, such as immunotherapies, chemotherapies, and BTKis, relapse and drug resistance continue to pose significant challenges in clinical practice. There is a substantial unmet medical need for new treatment options for patients with CLL/SLL.

Lisaftoclax (APG-2575) is an innovative orally administered Bcl-2 selective inhibitor developed by Ascentage Pharma to treat various malignancies. It works by selectively blocking the antiapoptotic protein Bcl-2, thereby restoring the normal apoptosis process in cancer cells. With its strong global best-in-class potential, lisaftoclax (APG-2575) is the first Bcl-2 inhibitor in China and the second globally to demonstrate compelling clinical activity and enter a pivotal study.

Currently, Ascentage Pharma has initiated a total of 19 global clinical studies of lisaftoclax (APG-2575), treating more than 600 patients, including over 300 patients with CLL/SLL. Previous studies have shown that lisaftoclax, either alone or in combination with other drugs, has significant therapeutic potential as a safe, effective, and easy-to-use therapy for CLL/SLL patients. Preliminary results from a global Phase II study revealed promising objective response rates (ORRs) with lisaftoclax combined with the next-generation BTKi acalabrutinib, reaching 100% ORR in treatment-naïve patients and 98% in relapsed/refractory patients. The combination regimens demonstrated a safety profile comparable to lisaftoclax monotherapy, with a very low incidence of tumor lysis syndrome (TLS). Additionally, the study of lisaftoclax (APG-2575) was initiated with a patient-friendly daily dose ramp-up schedule, allowing them to quickly reach target doses.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, expressed that while significant progress has been made in targeted therapies, there still exist major clinical challenges and urgent unmet medical needs for safe and effective novel therapies. Lisaftoclax, a critical drug candidate in their apoptosis-targeted pipeline, has shown promising efficacy and safety in earlier studies. The FDA’s clearance for the global Phase III study represents a major milestone in lisaftoclax’s development. The company remains committed to fulfilling its mission of addressing unmet clinical needs and is determined to advance the global Phase III study of lisaftoclax (APG-2575) to provide patients worldwide with this novel therapeutic option as soon as possible.

FDA Issues CRL to BLA Resubmission for Remestemcel-L in Pediatric Steroid-Refractory aGVHD

The FDA has issued a response letter regarding the biologics license application (BLA) resubmission for remestemcel-L (Ryoncil), stating that more data is required to support the drug’s approval for pediatric patients with steroid-refractory acute graft-vs-host disease (aGVHD). To address this, additional data will be gathered through a targeted and controlled study in adult patients with the highest risk and greatest mortality.

Pilot data obtained through the company’s emergency investigational new drug program in adults showed a survival benefit with remestemcel-L in the target population for the trial. The company is now collaborating with investigators across the United States to plan the adult follow-on study protocol and will hold a Type A meeting with the FDA within 45 days to discuss the trial design.

Before the resubmission, Mesoblast addressed outstanding chemistry, manufacturing, and controls issues according to FDA guidance before initiating another trial. The FDA completed a pre-license inspection of the manufacturing facility without issuing any Form 483 or finding any objectionable conditions. Additionally, in the resubmission review, the FDA acknowledged that changes made to the assay appeared to improve its performance for subsequent research.

In a previous single-arm phase 3 trial involving 54 children with steroid-refractory aGVHD, the prespecified primary endpoint was met, and the company had agreed with the FDA on the trial’s terms. In August 2020, the FDA’s Oncologic Drugs Advisory Committee voted 9:1 in favor of remestemcel-L’s efficacy in pediatric patients. However, in September 2020, the FDA recommended taking additional steps to obtain approval.

The BLA was resubmitted in January 2023 and accepted for review in March 2023. It included long-term follow-up data from the phase 3 trial led by the Center for International Blood and Marrow Transplant Research, showing that half of the patients remained alive after more than 4 years of follow-up. The resubmission also presented a post-hoc propensity matched study demonstrating a 6-month survival rate of 67% with remestemcel-L, compared to 10% with other unapproved therapies, in the highest-risk patients defined by the Mount Sinai Acute GVHD International Consortium. Mesoblast stated in the press release that these pediatric data provide further support for the use of remestemcel-L in the proposed study in high-risk adults with steroid-refractory acute GVHD.

Bavarian Nordic Reports Positive Phase 3 Topline Results for Chikungunya Virus Vaccine in Adults and Adolescents

On August 6, 2023, Bavarian Nordic A/S (OMX: BAVA) reported encouraging top-line findings from a Phase 3 clinical trial (NCT05072080) for its CHIKV VLP (PXVX0317) chikungunya virus vaccine. The trial, which was randomized, double-blind, and placebo-controlled, focused on adults and adolescents aged 12 to 64 years. Chikungunya presents a substantial burden on public health and affected communities. This mosquito-borne viral infection can cause debilitating joint pain, fever, and fatigue, often leading to long-lasting discomfort and reduced quality of life for those affected. 

The study involved 3,254 participants who were divided into groups to receive a single intramuscular dose of either CHIKV VLP or a placebo. The findings up until day 22 after vaccination indicated that CHIKV VLP triggered a robust immune response in both healthy adolescents and adults. This was evidenced by the significant production of chikungunya-neutralizing antibodies in 98% of those who received the active vaccine. The levels of these potent neutralizing antibodies met or surpassed the established threshold accepted by regulatory bodies for indicating protection against the virus. Consequently, the study’s primary goals were successfully achieved.

We are highly encouraged by the positive topline results now demonstrated in both Phase 3 studies of our chikungunya vaccine candidate. Our focus remains to finalize the studies and prepare for regulatory submissions next year. With a fast and durable response, our vaccine has the potential to be the best in class to prevent chikungunya infections in adolescents to elderly adults. Chikungunya which can often result in a severe and incapacitating disease affects large parts of the world, and with international travel on the rise again, our CHIKV vaccine offers a significant opportunity to address this large unmet medical need.

Paul Chaplin, President and CEO of Bavarian Nordic

Of significant note, CHIKV VLP triggered notable levels of neutralizing antibodies in 97% of participants just two weeks after vaccination, affirming the swift development of protective immunity. These immune responses were not only strong but also enduring; 6 months after vaccination, 86% of subjects maintained seroprotective levels of neutralizing antibodies. Moreover, CHIKV VLP demonstrated excellent tolerability within this group of adolescents and adults, with any adverse events primarily characterized as mild or moderate in severity.

Earlier, in June 2023, Bavarian Nordic unveiled encouraging top-level findings from a Phase 3 trial involving healthy adults aged 65 years and older (NCT05349617). This study exhibited that CHIKV VLP prompted chikungunya-neutralizing antibodies in 87% of those who received the vaccine within 22 days of a single dosage. Furthermore, the vaccine was well-received in terms of tolerability. The outcomes of both these trials will serve as the foundation for the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in 2024. These submissions are aimed at supporting the potential introduction of the vaccine in 2025.

Chikungunya outbreaks can overwhelm healthcare systems, leading to increased hospitalizations and medical expenditures. The economic impact also extends to reduced workforce productivity due to illness and absenteeism. With its potential to cause widespread epidemics, Chikungunya places a significant strain on healthcare resources, economies, and the overall well-being of affected regions. Globally, several major pharma and biotech companies are actively working in the Chikungunya therapeutics market to improve the treatment dynamics. 

US FDA Grants Orphan Drug Designation to ABM-1310 for the Treatment of Glioblastoma Harboring BRAF V600 Mutation

On Aug. 2, 2023, ABM Therapeutics (ABM) communicated that the US FDA has granted Orphan Drug Designation (ODD) to its therapy, ABM-1310, an innovative small molecule BRAF inhibitor created by the company. This designation is intended for the therapeutic use of ABM-1310 in patients who have Glioblastoma (GBM) and possess the BRAF V600 mutation.

ABM-1310, an orally administered medication, exhibits notable features including a strong preference for BRAF mutations, excellent water solubility, and the capability to effectively cross the blood-brain barrier. This groundbreaking drug is the result of ABM’s independent developmental efforts. ABM-1310 is currently undergoing Phase I trials at various clinical sites both in the United States and China, focusing on its application in treating advanced solid tumors marked by the BRAF V600 mutation. The interim findings from its Phase I study in the U.S. were unveiled at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2023. These results showcased the encouraging anti-cancer effects of ABM-1310 and its favorable safety profile among patients with advanced BRAF V600 mutant solid tumors, including primary brain tumors like GBM and other gliomas. A fresh Phase I clinical trial, specifically directed towards GBM, has recently been initiated in China.

GBM represents a formidable and fiercely aggressive brain tumor that poses considerable treatment difficulties. The intricate process of tumor formation and its resistance to therapy contribute to the considerable challenges associated with treating Glioblastoma. As per DelveInsight, the total incident population of Glioblastoma in the 7MM was 32,546 in 2021. In the United States, incident cases were observed to be 13,251 in 2021.  The total incident cases of Glioblastoma patients in the 7MM were maximum in males as compared to females in the 7MM. Traditional approaches such as surgical removal, radiation treatment, and chemotherapy continue to fall short of optimal outcomes. Given the scarcity of viable treatment alternatives following disease advancement, there is a substantial need for the creation of more potent therapeutic solutions. Globally, several major pharmaceutical and biotech companies are actively working in the Glioblastoma market to develop effective treatment options.