Denali Therapeutics and Biogen faced a setback as the Phase III trial for their Parkinson's disease drug, DNL-151, was terminated, impacting its approval prospects. Meanwhile, LIB Therapeutics reported positive Phase III results for lerodalcibep in treating heterozygous familial hypercholesterolemia, and AstraZeneca and Incyte saw advancements in their respective clinical programs.
DNL-151 Phase III Trial Termination
The Phase III trial (NCT05418673) evaluating Denali Therapeutics' DNL-151 in early-stage Parkinson's disease patients with a pathogenic leucine-rich repeat kinase 2 (LRRK2) gene variant was terminated. The trial's termination, attributed to the sponsor's decision, led to a 14-point decrease in the drug's Likelihood of Approval (LoA), bringing it down to 14%. The study had enrolled only six patients. DNL-151, an oral LRRK2 inhibitor co-developed by Denali and Biogen, aimed to assess the drug's safety and efficacy in this specific patient population.
Lerodalcibep's Positive Phase III Data in HeFH
LIB Therapeutics announced positive results from its Phase III LIBerate-HeFH study (NCT04797104), evaluating lerodalcibep in patients with heterozygous familial hypercholesterolemia (HeFH) already on maximally tolerated statin therapy. The trial achieved both co-primary endpoints, demonstrating a statistically significant 58.6% placebo-adjusted reduction in mean LDL cholesterol levels after 24 weeks in the intent-to-treat population. Additionally, a 65% reduction in LDL cholesterol was observed at the mean of weeks 22 and 24. The drug also exhibited a favorable safety profile, with treatment-emergent adverse events similar to placebo. As a result, lerodalcibep's LoA increased by 11 points to 65%. Lerodalcibep is a next-generation PCSK9 inhibitor being developed as an adjunct therapy for patients requiring additional LDL cholesterol reduction.
AstraZeneca's MEDI-7352 Phase IIb Completion in Osteoarthritis Pain
AstraZeneca's MEDI-7352 saw its Phase Transition Success Rate (PTSR) increase by six points to 45% in osteoarthritis pain following the completion of the Phase IIb BESPOKE trial (NCT04675034). This trial investigated the efficacy and safety of multiple doses of MEDI-7352 in participants with moderate to severe chronic pain lasting three months or longer and uncontrolled by standard treatments. The study also assessed the drug's immunogenicity, pharmacodynamics, and pharmacokinetics, with the primary endpoint being the change in the weekly average of daily numerical rating scale pain scores from baseline until week 12. MEDI-7352 is a nerve growth factor and tumor necrosis factor inhibiting bispecific antibody.
Incyte's Itacitinib PTSR Increase in Cytokine Release Syndrome
Incyte's itacitinib experienced a nine-point jump in its PTSR in cytokine release syndrome (CRS) after the completion of a Phase II trial (NCT04071366). The trial evaluated the safety and efficacy of oral itacitinib for the prevention of CRS in 112 patients receiving approved immune effector cell (IEC) therapy for hematologic malignancies. Itacitinib is a Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities.
