Otsuka and Lunbeck report positive Phase III results in agitation in Alzheimer’s, Acer’s vEDS program hits Phase III and BridgeBio’s primary hyperoxaluria type 1 program progresses.
There’s plenty of clinical trial news every week, as companies work to develop new and exciting drugs to treat serious illnesses. Here’s a look at just some of last week’s clinical trial announcements.
Otsuka Pharmaceutical and Lundbeck reported positive Phase III results for Rexulti (brexpiprazole) for agitation in Alzheimer’s dementia patients. They expect to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration based on the data. The drug is already approved for schizophrenia and as adjunctive therapy for major depressive disorder. In the study, which has not yet been fully analyzed, the partners report a statistically significant difference in mean changes from baseline to week 12 in an assessment of agitation.
Acer Therapeutics initiated its Phase III DISCOVER trial of Edisivo (cliprolol) for patients with COL3A1-positive vascular Ehlers-Danlos Syndrome (vEDS). vEDS is an autosomal inherited disorder caused by mutations in the genes responsible for the structure, production, or processing of collagen. EDS is a spectrum disorder with a range of symptoms, the most serious of which is vEDS, also called vEDS type IV, usually caused by a COL3A1 gene mutation, which decreases collagen levels. vEDS causes abnormal fragility in blood vessels, which can result in aneurysms, arteriovenous fistulas, arterial dissections, and spontaneous vascular ruptures, which can be life-threatening.
BridgeBio Pharma announced positive Phase I data for BBP-711, which is being developed for primary hyperoxaluria type 1 (PH1) and recurrent kidney stone formers. The drug is an orally-administered small molecule glycolate oxidase (GO) inhibitor. The study demonstrated effective pharmacokinetic parameters and rapid and clinically meaningful pharmacodynamic increases in plasma glycolate of 10-15-fold above baseline levels. It was well tolerated with few emergent adverse events, all of which were mild or moderate. Based on the data the company plans to launch a proof-of-concept Phase II study in adult recurrent kidney stone formers with elevated urinary oxalate excretion by the end of the year.
Basilea Pharmaceutica announced positive topline data from the Phase III ERADICATE trial of ceftobiprole for adults with bacterial bloodstream infections caused by Staphylococcus aureus (SAB). The trial enrolled 290 patients with complicated SAB, including right-sided endocarditis. The drug hit the pre-specified efficacy objective of overall success in the modified intent-to-treat (mITT) population at 70 days after randomization, within the pre-specified non-inferiority margin of 15% compared to daptomycin, with or without aztreonam. The overall success rate was 69.8% with ceftobiprole compared to 68.7% with daptomycin, with or without aztreonam. Ceftobiprole medocaril, the prodrug of the active moiety ceftobiprole, is a cephalosporin antibody for IV administration.
Jazz Pharmaceuticals announced topline results from the Phase III RELEASE MSS1 trial of nabiximols oromucosal spray on clinical measures of spasticity in people with multiple sclerosis. The study failed to hit the primary endpoint of change in Lower Limb Muscle Tone-6 (LLMT-6) between baseline and Day 21, as measured by the Modified Ashworth Scale (MAS). The drug is a complex botanical mixture formulated from extracts of the cannabis sativa plant and contains the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) as well as other cannabinoid and non-cannabinoid components. It is marketed outside the U.S. as Sativex for adults with moderate to severe spasticity due to MS who have not responded adequately to other anti-spasticity drugs.
Corcept Therapeutics plans to initiate a Phase III trial of relacorilant plus nab-paclitaxel in patients with recurrent, platinum-resistant ovarian cancer after announcing positive results from its Phase II trial of the drug. The ROSELLA trial will enroll 360 women, randomized 1:1, to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone. The primary endpoint will be progression-free survival (PFS) with overall survival (OS) a key secondary endpoint. All patients will have received previous bevacizumab therapy, the typical standard of care in the U.S. for patients with platinum-resistant ovarian cancer. Relacorilant is a non-steroidal, selective glucocorticoid receptor modulator.
Lexicon Pharmaceuticals announced topline data from its Phase II RELIEF-DPN-1 trial of LX9211 in painful diabetic neuropathy. The drug hit the primary endpoint, demonstrating a statistically significant decrease in average daily pain score (ADPS) at week 6 compared to placebo in the low dose arm, with results that plateaued in the high dose arm. Adverse events were more frequent in the drug treatment arms and at the higher dose, with the most common being dizziness, headache and nausea, although almost all were mild or moderate. LX9211 is a potent, orally delivered, selective small molecule inhibitor of adaptor-associated kinase 1 (AAK1).
Sanofi reported that the FDA has placed a partial clinical hold on several trials involving tolebrutinib. The drug, a brain-penetrant Bruton’s tyrosine kinase inhibitor, is being developed for relapsing forms of multiple sclerosis (MS), myasthenia gravis (MG), non-relapsing secondary progressive MS (nRSPMS) and primary progressive MS (PPMS). Participants in the study who have been receiving the drug for more than 60 days will be allowed to continue. Sanofi indicated that the majority of the affected individuals already had complications that predisposed them to drug-induced liver injury. The liver injury caused the FDA to impose a partial hold.
AstraZeneca announced positive high-level data from a planned interim analysis of the Phase III AEGEAN study of Imfinzi (durvalumab) with neoadjuvant chemotherapy prior to surgery in patients with resectable non-small cell lung cancer (NSCLC). The data demonstrated a statistically significant improvement in pathologic complete response (pCR) compared to neoadjuvant chemotherapy alone. The data also showed a statistically significant improvement in major pathologic response. Imfinzi is an anti-PD-L1 checkpoint inhibitor.
BeiGene announced new data from the Phase III RATIONALE L306 study of tislelizumab in advanced or metastatic esophageal squamous cell carcinoma (ESCC) in patients who had yet to receive systemic treatment. The combination decreased the risk of death by 34% compared to chemotherapy plus placebo. There were also significant improvements in progression-free survival and overall response rate. Tislelizumab is a humanized IgG4 anti-PD-1 checkpoint inhibitor.
