Akeso Reports Positive Phase 3 Results for Ivonescimab in Lung Cancer, Building on Recent FDA Approval Success
• Akeso announced positive Phase 3 results for ivonescimab, a novel PD-1/VEGF bispecific antibody, demonstrating superior tumor progression control when combined with chemotherapy compared to PD-1 inhibitor plus chemotherapy in lung cancer patients.
• The company recently secured FDA approval for penpulimab, its PD-1 monoclonal antibody, for first-line treatment of nasopharyngeal carcinoma, marking significant expansion of Akeso's oncology portfolio.
• Akeso and Summit Therapeutics are advancing ivonescimab in a global study against the standard Keytruda-chemotherapy regimen, with results expected in 2027, potentially challenging the current treatment paradigm in lung cancer.
Pacira BioSciences Advances Novel Gene Therapy for Knee Osteoarthritis with First Patient Dosed in Phase 2 Trial
• Pacira BioSciences has dosed the first patient in its Phase 2 ASCEND study evaluating PCRX-201, a locally administered gene therapy designed to treat osteoarthritis of the knee by boosting anti-inflammatory protein production.
• The innovative therapy utilizes Pacira's proprietary high-capacity adenovirus vector platform and features an inducible promoter that activates IL-1Ra expression during inflammation and deactivates when inflammation subsides.
• In previous Phase 1 trials, PCRX-201 demonstrated sustained pain relief for at least two years across all osteoarthritis severity levels, with topline results from the current two-part study expected by late 2026.
FDA Approves First Treatment for Hyperphagia in Prader-Willi Syndrome
• The FDA has approved VYKAT XR (diazoxide choline) as the first therapy specifically targeting hyperphagia in Prader-Willi syndrome, offering new hope to patients and families affected by this rare genetic disorder.
• Clinical trials demonstrated VYKAT XR's efficacy through a Phase 3 randomized withdrawal study, where patients switching to placebo showed significant worsening of hyperphagia compared to those remaining on the medication.
• Soleno Therapeutics expects to make VYKAT XR available in the US by April 2025, supported by the Soleno One patient support program to facilitate access to this breakthrough treatment.
Afuresertib Plus Paclitaxel Fails to Improve Survival in Platinum-Resistant Ovarian Cancer Trial
• Phase 2 PROFECTA-II/GOG-3044 trial shows afuresertib plus paclitaxel did not significantly improve progression-free or overall survival compared to paclitaxel alone in platinum-resistant ovarian cancer patients.
• Biomarker analysis suggests patients with higher pAKT expression (>1) may benefit more from the combination therapy, with median PFS of 5.4 months versus 2.9 months with paclitaxel alone.
• The combination therapy demonstrated a manageable safety profile but had higher rates of diarrhea (64.6% vs 19.1%) and more frequent treatment discontinuations (20.2% vs 6.4%) compared to paclitaxel monotherapy.
Nivolumab Shows Promising Results in dMMR/MSI-H Endometrial Cancer, Potentially Eliminating Need for Surgery
• Phase 2 NIVEC trial demonstrates 80% clinical complete response rate with nivolumab in patients with resectable dMMR/MSI-H endometrial cancer, allowing many to avoid surgery.
• No disease recurrence was observed during follow-up, and the treatment showed a manageable safety profile with only two grade 3/4 adverse events reported.
• The trial has now entered its second stage, recruiting an additional 15 patients after successfully demonstrating efficacy in stage 1 of the study.
Kodiak Sciences Completes Enrollment in GLOW2 Phase 3 Trial for Diabetic Retinopathy Treatment
• Kodiak Sciences has successfully enrolled over 250 patients in its GLOW2 Phase 3 trial of tarcocimab tedromer for diabetic retinopathy, with topline data expected in Q1 2026.
• The GLOW2 study mirrors the successful GLOW1 trial design with an additional loading dose, potentially offering a twice-yearly dosing regimen that could transform treatment for millions of diabetic retinopathy patients.
• If successful, Kodiak plans to file a single Biologics License Application for tarcocimab covering wet AMD, diabetic retinopathy, and retinal vein occlusion following completion of the DAYBREAK study in Q2 2026.
Denali Therapeutics' Tividenofusp Alfa Receives FDA Breakthrough Therapy Designation for Hunter Syndrome
• Denali Therapeutics' tividenofusp alfa (DNL310) has received Breakthrough Therapy Designation from the FDA for Hunter syndrome (MPS II).
• The designation aims to expedite the development and review of tividenofusp alfa, a potential improvement over existing therapies.
• Denali plans to submit a Biologics License Application (BLA) in early 2025 for accelerated approval of tividenofusp alfa.
• Tividenofusp alfa is designed to address both neurological and physical symptoms of Hunter syndrome by crossing the blood-brain barrier.
Corcept Therapeutics Submits New Drug Application for Relacorilant to Treat Cushing's Syndrome
• Corcept Therapeutics has submitted a New Drug Application to the FDA for relacorilant, a selective cortisol modulator designed to treat patients with endogenous hypercortisolism (Cushing's syndrome).
• The application is supported by positive results from multiple clinical trials, including the pivotal GRACE trial, Phase 3 GRADIENT study, and long-term extension studies, demonstrating improvements in various symptoms with an acceptable safety profile.
• Relacorilant showed no instances of serious adverse events common in current treatments, such as drug-induced adrenal insufficiency, hypokalemia, or QT prolongation, positioning it as a potential new standard of care.
Relacorilant Shows Durable Cardiometabolic Benefits in Cushing's Syndrome Patients
• Corcept Therapeutics' relacorilant demonstrates sustained improvements in cardiometabolic measures in patients with Cushing's syndrome over six years.
• The Phase III extension study showed statistically significant reductions in systolic (10.0 mm Hg) and diastolic (7.3 mm Hg) blood pressure after 24 months.
• Relacorilant is a selective cortisol modulator targeting the glucocorticoid receptor and is well-tolerated by patients with hypercortisolism.
• Corcept plans to submit a new drug application (NDA) for relacorilant, potentially establishing it as a new standard of care.
Mifepristone Demonstrates Significant HbA1c Reduction in CATALYST Trial for Hypercortisolism and Difficult-to-Control Type 2 Diabetes
• Mifepristone (Korlym) achieved a statistically significant 1.32% placebo-adjusted reduction in HbA1c in patients with hypercortisolism and difficult-to-control type 2 diabetes.
• The CATALYST trial revealed that approximately 23.8% of patients with difficult-to-control type 2 diabetes also have hypercortisolism.
• The safety profile of mifepristone in the CATALYST trial was consistent with its known safety profile, with no new adverse events identified.
• Complete results from the CATALYST trial will be presented at an upcoming medical conference, offering further insights into mifepristone's efficacy and safety.
Dazucorilant Fails Primary Endpoint in Phase 2 ALS Trial but Shows Survival Benefit
• Corcept Therapeutics' dazucorilant did not meet the primary endpoint in the DAZALS Phase 2 trial for amyotrophic lateral sclerosis (ALS).
• The study, involving 249 patients, aimed to slow the decline in motor skills as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
• A statistically significant survival benefit was observed in the 300 mg dazucorilant arm compared to placebo (p-value: 0.02) over the 24-week study.
• An open-label extension study is ongoing to assess long-term survival, with results expected in March 2025, and complete DAZALS results will be presented at a future medical conference.
Durvalumab Gains Priority Review for Muscle-Invasive Bladder Cancer Treatment
• The FDA has granted priority review to durvalumab (Imfinzi) for muscle-invasive bladder cancer (MIBC), potentially expediting its approval.
• Phase 3 NIAGARA trial data supports the application, showing a 32% reduction in disease progression or recurrence with perioperative durvalumab.
• The Imfinzi regimen also demonstrated a 25% reduction in the risk of death, offering a significant survival benefit.
• Regulatory decisions are anticipated in the second quarter of 2025, with potential implications for MIBC treatment standards.
Endocrinology Review: MariTide's Weight Loss, Semaglutide Eligibility, and CVD Benefits in T2D
• MariTide, a bispecific GLP-1 and GIPR agonist, demonstrated up to 20% weight loss in a phase 2 trial, showing promise for obesity treatment.
• A study indicated that over 50% of US adults may be eligible for semaglutide treatment based on current labeling for diabetes and weight management.
• The BPROAD trial highlighted that intensive blood pressure control (120 mmHg target) significantly reduces cardiovascular risk in type 2 diabetes patients.
• Semaglutide 2.4 mg was found to reduce knee osteoarthritis pain and improve physical function in obese individuals, according to the STEP 9 trial.
Relacorilant Plus Nab-Paclitaxel Shows Promise in Platinum-Resistant Ovarian Cancer
• Relacorilant, a selective glucocorticoid receptor modulator, combined with nab-paclitaxel, demonstrates potential in treating platinum-resistant ovarian cancer.
• Phase 2 trial data supports the combination's efficacy, leading to the ongoing phase 3 ROSELLA trial to further evaluate its benefits.
• The treatment approach targets the glucocorticoid receptor, offering a novel strategy in managing this challenging gynecologic malignancy.
Cell Therapy and Targeted Therapies Dominate Oncology Advances in Early 2025
• The FDA issued a CRL for Atara Biotherapeutics' tabelecleucel due to third-party manufacturing issues, not efficacy or safety data, delaying potential approval for EBV+ PTLD.
• EsoBiotec dosed the first patient in a trial for ESO-T01, an in vivo BCMA-directed CAR-T therapy for multiple myeloma, aiming for lower costs and simplified administration.
• Obecabtagene autoleucel (obe-cel) gained FDA approval for relapsed/refractory B-cell precursor ALL, offering a less toxic CD19-directed CAR T-cell therapy option.
• Arlocabtagene autoleucel (arlo-cel) shows promise in heavily pretreated relapsed/refractory multiple myeloma, eliciting a 48% complete response rate in phase 1 studies.
Relacorilant Fails to Meet Primary Endpoint in GRADIENT Trial for Cushing's Syndrome
• Corcept Therapeutics' Phase III GRADIENT trial of relacorilant in Cushing's syndrome did not meet its primary endpoint of statistically significant improvement in systolic blood pressure.
• Despite missing the primary endpoint, patients on relacorilant showed clinically meaningful improvements in hypertension, hyperglycemia, weight, and body composition compared to baseline.
• The GRADIENT trial's data, along with the GRACE trial results, will support Corcept's New Drug Application (NDA) submission for relacorilant, expected by year-end.
• Relacorilant was well-tolerated in the GRADIENT trial, with no reported cases of hypokalemia, endometrial hypertrophy, adrenal insufficiency, or QT prolongation.
Corcept's Relacorilant Shows Promise in Cushing's Syndrome Treatment
• Corcept Therapeutics' GRADIENT trial demonstrates relacorilant's efficacy in treating Cushing's syndrome, showing clinically meaningful improvements in hypercortisolism signs and symptoms.
• The Phase 3 trial supports the New Drug Application (NDA) for relacorilant, expected to be submitted by year-end, offering a potential new treatment option.
• Relacorilant was well-tolerated in the GRADIENT study, with a safety profile consistent with previous trials, and no instances of hypokalemia or other severe adverse effects.
• Corcept's revenue increased by 48% compared to the same period in 2023, with increased revenue guidance for 2024.
FDA Accepts UroGen's NDA for UGN-102 in Low-Grade Non-Muscle Invasive Bladder Cancer
• The FDA has accepted UroGen Pharma's NDA for UGN-102 (mitomycin) intravesical solution for treating low-grade, intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).
• UGN-102, if approved, would be the first FDA-approved treatment for LG-IR-NMIBC, offering a novel non-surgical approach.
• The NDA is supported by Phase 3 ENVISION trial data, demonstrating a 79.6% complete response rate at 3 months and an 82.3% duration of response at 12 months.
• The FDA has set a PDUFA target action date of June 13, 2025, for the decision on UGN-102.
Relacorilant and Surgery Improve Hemostatic Markers in Cushing's Syndrome
• A study shows that hypercoagulopathy, a complication in Cushing's Syndrome (CS), improves with both relacorilant treatment and surgery.
• Relacorilant, a selective glucocorticoid receptor modulator (SGRM), demonstrated improvements in coagulation markers after 3-4 months of treatment.
• Surgical intervention also led to improvements in coagulation markers within an average of 6 months post-operation in CS patients.
• The study suggests relacorilant may offer a beneficial treatment option for CS patients, particularly those at high risk of VTE or not suitable for surgery.
MIROCALS Trial Results: Low-Dose IL-2 Shows Potential Benefit for Subset of MND Patients
• The MIROCALS trial testing low-dose interleukin-2 (IL-2) for motor neurone disease (MND) failed to meet its primary endpoint for the overall population, with results published in The Lancet on May 9, 2025.
• Post-hoc analysis revealed a potential benefit for patients with slower disease progression, identified by low neurofilament levels, showing 18% higher survival rates and 23% decreased functional decline compared to placebo.
• The UK MND Clinical Studies Group is currently evaluating the complex findings to determine next steps, with three MND organizations collaborating to expedite access to proven treatments.
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