Iovance Biotherapeutics' cellular immunotherapy MDA-TIL for oncology experienced a setback as a Phase II investigator-led trial was terminated due to lack of efficacy. This termination led to a significant drop in its Phase Transition Success Rate (PTSR) across several cancer types. The Phase I/II trial (NCT03610490), led by the M.D. Anderson Cancer Center, aimed to evaluate the objective response rate (ORR) over five years using Iovance’s autologous expanded tumor-infiltrating lymphocytes immunotherapy.
The PTSR for MDA-TIL fell by 24 points to 7% in ovarian cancer, 16 points to 7% in colorectal cancer, and 21 points to 12% in pancreatic ductal adenocarcinoma. Iovance is collaborating with the National Cancer Institute and Bristol Myers Squibb to develop this immunotherapy, which targets immunodominant minor histocompatibility antigens to reduce T cell responses and cancer recurrence risk.
Sention Therapeutics Completes Phase II Hypothyroidism Trial
In contrast, Sention Therapeutics' ST-1891 saw its PTSR increase following the completion of a Phase II trial in hypothyroidism. The drug's PTSR rose by nine points, reaching 22% in this indication. The multicenter, randomized, double-blind Phase II study (NCT05412979) assessed the safety and efficacy of ST-1891 compared to Merck’s Euthyrox (levothyroxine sodium) in 490 participants with primary hypothyroidism. The primary endpoints focused on comparing the dosing conversion factor of Euthyrox to ST-1891 over 52 weeks and the percentage of patients achieving thyroid-stimulating hormone levels within the standard reference range within 26 weeks.
ST-1891, an orally administered hormone replacement therapy, works by replacing diminished T3/T4 hormone levels in hypothyroidism patients.
Karyopharm's Selinexor Trial Halted in Metastatic Melanoma
Karyopharm Therapeutics' Xpovio (selinexor) experienced a PTSR decrease in metastatic melanoma after a Phase II trial was terminated. The PTSR dropped by 14 points to 11%. The Phase II trial (NCT04768881) was terminated by the sponsor due to a lack of sufficient anti-melanoma tumor signal for the combination of selinexor and pembrolizumab, according to the ClinicalTrials.gov listing. The open-label, multi-center study aimed to evaluate the safety and efficacy of selinexor in combination with Merck’s Keytruda (pembrolizumab) in recurrent advanced melanoma, enrolling 15 patients before termination.
Selinexor is a selective inhibitor of nuclear export, being developed for various cancer indications.
Worg Pharmaceuticals Suspends Graves’ Disease Trial
Worg Pharmaceuticals Hangzhou’s WP-1302 saw its PTSR in Graves’ disease decrease by 16 points to 4% after a Phase II study was suspended. The Phase II trial (NCT06240455) was suspended because it was not feasible to recruit suitable subjects. The double-blind, placebo-controlled study aimed to assess the efficacy and safety of WP-1302 in preventing disease relapse following methimazole withdrawal in subjects with Graves’ disease.
WP-1302 functions as a tolerogen designed to induce immunological tolerance. The peptide vaccine is being developed for Graves’ disease.
Armata Pharmaceuticals Completes Bronchiectasis Trial
Armata Pharmaceuticals’ APPA-02 saw its PTSR increase after a Phase II trial was completed. The drug candidate’s PTSR increased by seven points in bronchiectasis to 43%. The Phase II trial (NCT05616221) evaluated the safety, phage kinetics, and efficacy of APPA-02 in treating subjects with non-cystic fibrosis bronchiectasis, enrolling 48 patients. APPA-02 is a synthetic phage that can kill specific bacteria through the expression of biofilm-degrading enzymes and antimicrobial peptides, targeting multidrug-resistant chronic pulmonary Pseudomonas aeruginosa infections in cystic fibrosis patients and non-CF bronchiectasis (NCFB).
Stealth BioTherapeutics' Elamipretide Shows Promise in Friedreich's Ataxia
Stealth BioTherapeutics’ Bendavia (elamipretide hydrochloride) saw a nine-point increase in its PTSR, settling at 38% in Friedreich’s ataxia, following the completion of a Phase II investigator-led trial (NCT05168774). The Children’s Hospital of Philadelphia led the study, investigating the safety, tolerability, and efficacy of Bendavia in treating advanced symptoms of Friedreich ataxia, measuring the change in high-contrast visual acuity as its primary outcome.
Bendavia is a cardiolipin binder that treats Friedreich’s ataxia by enhancing ATP synthesis in multiple organs, including the heart, kidney, neurons, and skeletal muscle. It prevents the opening of the mitochondrial membrane permeability transition pore (mPTP) during reperfusion, potentially mitigating tissue necrosis and apoptosis. Stealth has been granted orphan drug designation for Bendavia in treating Friedreich’s ataxia and is also investigating it for Barth syndrome, Duchenne muscular dystrophy, and various mitochondrial diseases.
