Jared Baeten, MD, PhD, Senior Vice President and Head of the Virology Therapeutic Area at Gilead Sciences, stated, “The future of HIV treatment focuses on individualized care, offering long-acting solutions designed to address the specific needs and preferences of those affected by HIV. A universal approach won’t suffice; the complexities of HIV care necessitate prioritizing individuals in the development of biomedical advancements. Our ongoing efforts aim to provide options for everyone living with HIV. The findings shared at IDWeek highlight our dedication to ongoing scientific exploration that seeks to reshape the landscape of HIV treatment.”
Islatravir in combination with lenacapavir, is currently under investigation and has not received global approval. The safety and effectiveness of this combination have yet to be determined. Lenacapavir is being explored in several ongoing clinical trials, both early and late-stage, and may provide a range of personalized treatment options that can be tailored to the needs of individuals living with HIV. However, its application for treating HIV in virologically suppressed patients is still investigational and has not been approved worldwide.
REGENXBIO Unveils Promising Phase II Data on ABBV-RGX-314 for Bilateral Wet AMD at AAO 2024
REGENXBIO Inc. reported encouraging results from the Phase II sub-study focusing on the fellow eye, which assessed the subretinal delivery of ABBV-RGX-314 in patients with bilateral wet age-related macular degeneration (wet AMD). These findings were shared by Arshad Khanani, M.D., M.A., FASRS, Director of Clinical Research at Sierra Eye Associates in Reno, NV, during the American Academy of Ophthalmology (AAO) meeting.
The findings presented at the AAO from the Phase II sub-study, which is the first to assess a gene therapy in fellow eyes for wet AMD, indicate that ABBV-RGX-314 has the potential to treat patients with bilateral disease. This adds to the substantial evidence supporting ABBV-RGX-314’s ability to influence the treatment approach for wet AMD patients,” stated Curran Simpson, President and CEO of REGENXBIO. “With a larger number of patients treated and the longest-term data available for any gene therapy program addressing wet AMD, REGENXBIO, in collaboration with AbbVie, is well-positioned to introduce the first gene therapy aimed at preserving long-term vision for millions of patients worldwide suffering from wet AMD.
The fellow eye sub-study aimed to assess the safety and efficacy of a single dose (1.3×10^11 GC/eye) of ABBV-RGX-314 administered via subretinal delivery in the fellow eye of patients who had already been treated. The second eye received ABBV-RGX-314 approximately one year or more after the first eye’s treatment. This dosage is currently being tested in the ongoing pivotal trials for ABBV-RGX-314 and is comparable to one of the doses examined in Phase I/IIa trial, which showed a sustained treatment effect for up to four years in a long-term follow-up study.
The fellow eye sub-study data from nine months involves nine patients who were administered ABBV-RGX-314 through subretinal delivery in Phase I/IIa or bridging studies and chose to receive treatment in their other eye. Before the administration of ABBV-RGX-314, these patients experienced a significant treatment burden in the fellow eye, averaging nine anti-VEGF injections in the year leading up to their participation in the study, which included anti-VEGF injections aimed at providing longer-lasting results.
U.S. FDA Approves Astellas’ VYLOY for Advanced Stages of Gastric and GEJ Cancers
Astellas Pharma Inc. has announced that the FDA has approved VYLOY (zolbetuximab-clzb) to be used in combination with fluoropyrimidine- and platinum-based chemotherapy as a first-line treatment for adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma, specifically for those whose tumors are claudin (CLDN) 18.2 positive, as confirmed by an FDA-approved test. VYLOY is the first and only therapy targeting CLDN18.2 that has received approval in the U.S.
The approval was granted based on findings from the Phase III SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study assessed the efficacy of VYLOY combined with mFOLFOX6 (which includes oxaliplatin, leucovorin, and fluorouracil) against a placebo with mFOLFOX6. Meanwhile, the GLOW study compared VYLOY plus CAPOX (which consists of capecitabine and oxaliplatin) to a placebo with CAPOX.
Both trials achieved their primary goal of progression-free survival (PFS) and a key secondary goal of overall survival (OS) for patients receiving VYLOY along with chemotherapy, compared to those on placebo with chemotherapy. In both SPOTLIGHT and GLOW trials, the most frequently reported all-grade treatment-emergent adverse events (TEAEs) in the VYLOY groups were nausea, vomiting, and loss of appetite.
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development at Astellas, stated, “The approval of VYLOY as the first and only targeted therapy for patients with CLDN18.2-positive cancers in the U.S. represents a significant step forward in our ongoing commitment to advancing science for serious illnesses like gastric and GEJ cancers, which are often diagnosed at advanced stages. This accomplishment stems from years of dedicated research and development aimed at targeting a novel biomarker. We extend our gratitude to the patients, researchers, and Astellas team members who have contributed to this crucial progress for patients.”
Following the FDA decision, VYLOY has received approval in five countries: Japan, the United Kingdom, the European Union, South Korea, and the United States. The Ministry of Health, Labour, and Welfare in Japan was the first to approve VYLOY for use on March 26, 2024. In August, the UK Medicines and Healthcare products Regulatory Agency also approved VYLOY. The European Commission followed suit in September by providing marketing authorization for the therapy within the EU, and the Ministry of Food and Drug Safety in South Korea approved it as well. Astellas has submitted additional applications for VYLOY to various regulatory bodies globally, and these reviews are currently in progress.
Merck’s CAPVAXIVE Shows Promising Immune Response in High-Risk Adults for Pneumococcal Disease
Merck shared findings from the STRIDE-8 Phase III trial assessing CAPVAXIVE (Pneumococcal 21-valent Conjugate Vaccine) during IDWeek 2024 in Los Angeles, California. This study investigated the immunogenicity, safety, and tolerability of CAPVAXIVE compared to PCV15 (pneumococcal 15-valent conjugate vaccine) in conjunction with PPSV23 (pneumococcal 23-valent polysaccharide vaccine) among vaccine-naïve adults aged 18 to 64 with specific chronic conditions that increase their risk of pneumococcal disease.
The main findings from the STRIDE-8 trial include:
– CAPVAXIVE demonstrated immunogenicity for all 21 serotypes (or strains) in the vaccine, as indicated by the geometric mean titers (GMTs) for serotype-specific opsonophagocytic activity (OPA) (the primary immunogenicity goal) and the geometric mean concentrations (GMCs) of immunoglobulin G (IgG) (the secondary immunogenicity goal) at Day 30.
– The immune responses generated by CAPVAXIVE were similar to those elicited by PCV15 followed by PPSV23 for the 13 common serotypes and were higher for the eight unique serotypes in CAPVAXIVE, based on OPA GMTs and IgG GMCs measured 30 days after vaccination.
– The rates of adverse events (AEs), including injection-site, systemic, and vaccine-related AEs, were numerically lower in the V116 + placebo group compared to the PCV15 + PPSV23 group.
Dr. Walter Orenstein, a professor emeritus at Emory University and a member of Merck’s Scientific Advisory Committee, stated, “Adults suffering from chronic medical conditions like kidney disease or diabetes are especially at risk for invasive pneumococcal disease, which can heighten their chances of severe illness. These findings further illustrate that the extensive serotype coverage offered by CAPVAXIVE can help safeguard vulnerable adults from invasive disease.”
Alongside STRIDE-8, Merck shared findings from a targeted literature review assessing the clinical and economic impact of pneumococcal disease in adults in the U.S. The review revealed that Black adults and those living in rural areas with lower education and income levels experience a greater disease burden and have lower pneumococcal vaccination rates.
Additionally, data from a modeling study examining the health effects of introducing CAPVAXIVE in U.S. adults were presented. This study determined that implementing CAPVAXIVE led to a 33.9% reduction in invasive pneumococcal disease (IPD) incidence over 10 years, alongside ongoing pediatric PCV vaccination. This reduction translated to about 14,000 fewer cases with CAPVAXIVE compared to PCV20 (the 20-valent pneumococcal conjugate vaccine) after the same period.
FDA Delays Amgen’s LUMAKRAS Colorectal Cancer Approval Decision Until Early 2025
The US regulators have postponed their review of Amgen’s LUMAKRAS (sotorasib) for second-line colorectal cancer (CRC) by three months, with a new potential approval date set for January 17 of next year. This delay alleviates some competitive pressure on Bristol Myers Squibb’s competing KRAS-blocking drug, KRAZATI (adagrasib).
The company is aiming for LUMAKRAS to be approved in combination with the EGFR antibody Vectibix (panitumumab) for chemorefractory KRAS G12C–mutated metastatic CRC, a submission backed by the Phase III CodeBreaK 300 trial.
The study presented at this year’s American Society of Clinical Oncology (ASCO) annual meeting indicated promising survival trends for the combination treatment. In the higher 960-mg dose of LUMAKRAS combined with Vectibix, the median overall survival was not reached, while the median overall survival for the investigator’s choice therapy was 10.3 months, resulting in a hazard ratio of 0.70. The objective response rate for the higher-dose combination was 30.2%, which included one complete response.
This delay comes after a previous setback for Amgen’s KRAS program when the FDA denied the company’s request for full approval of LUMAKRAS for non-small-cell lung cancer late last year. The drug currently has accelerated approval for this indication, which it received in 2021.
The regulatory delay may give Bristol Myers Squibb additional time to strengthen KRAZATI’s position in colorectal cancer without facing direct competition from LUMAKRAS. KRAZATI initially received accelerated approval for advanced non-small cell lung cancer in 2022, and in June, it received an expanded indication for use alongside cetuximab in patients with KRASG12C mutations who have locally advanced or metastatic CRC and have been previously treated.
