This week on Pipeline Moves, we kick off by looking at the termination of a Phase III trial in parkinson’s disease. On a good note, we investigate the completions of Phase III trial in heterozygous familial hypercholesterolaemia, a Phase IIb study in osteoarthritis pain and a Phase II trial in cytokine release syndrome.

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Termination of Phase III trial

Denali Therapeutics’ DNL-151 saw its Likelihood of Approval (LoA) drop after a Phase III trial in Parkinson’s disease was terminated. The LoA decreased by 14 points to 14%.

The trial’s status on ClinicalTrials.gov changed from active, not recruiting to terminated on 6 September, with GlobalData evaluating the asset the next day. The study was terminated due to the sponsor’s decision, according to the trial registry.

LoA is identified via GlobalData’s analysis using a combination of machine learning and a proprietary algorithm. LoA can be calculated for a drug by considering characteristics like therapy area, indication and molecule type.

The Phase III trial (NCT05418673) assessed the safety and efficacy of oral DNL-151 in patients with early-stage Parkinson’s disease and pathogenic leucine-rich repeat kinase 2 (LRRK2) gene variant. The study enrolled six patients.

DNL-151 is an LRRK2 inhibitor and is co-developed by Denali and Biogen, who was listed as the sponsor of the trial on ClinicalTrials.gov.

Approval prospects rise in Phase III trial

LIB Therapeutics’ lerodalcibep saw its LoA in heterozygous familial hypercholesterolaemia (HeFH) rise after the publication of positive data from a Phase III trial. The LoA grew by 11 points to 65%.

On 28 August, the Cincinnati, Ohio-based company announced positive results from the Phase III LIBerate-HeFH study (NCT04797104), which investigated the efficacy, safety, and tolerability of subcutaneous injections of lerodalcibep in patients with HeFH on stable, maximally tolerated statin therapy with or without additional oral lipid lowering therapy, per the 28 August press release. GlobalData appraised the asset on 31 August.

The 478-subject trial achieved both of its co-primary endpoints, reporting 58.6% statistically significant placebo adjusted reductions in mean LDL cholesterol levels in the intent-to-treat population after 24 weeks. Similarly, the trial reported 65% LDL cholesterol reductions at the mean of week 22 and week 24, based on the announcement. The drug was reported to have had a favourable safety profile with treatment-emergent adverse events that were broadly similar to placebo.

Lerodalcibep is a next-generation PCSK9 inhibitor. The drug is developed as a potential adjunct therapy patients who are already on a diet and maximally tolerated statin therapy who require additional LDL cholesterol reduction, based on the company’s website. HeFH is a genetic condition that results in high LDL cholesterol levels.

AstraZeneca’s Phase IIb trial completion

AstraZeneca’s MEDI-7352 saw its Phase Transition Success Rate (PTSR) increase in osteoarthritis pain after the completion of a Phase IIb study. The PTSR grew by six points to 45%. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The Phase IIb BESPOKE trial’s (NCT04675034) status on its ClinicalTrials.gov listing changed from active, not recruiting to completed on 6 September, with GlobalData appraising the asset on 7 September. The Phase IIb trial investigated the efficacy and safety of multiple doses of MEDI-7352 in participants with moderate to severe chronic pain persistent for three months or longer, which is not controlled by standard treatments. The study also investigates the drug’s immunogenicity, pharmacodynamics and pharmacokinetics.

The trial measured the change in the weekly average of daily numerical rating scale pain scores from baseline until week 12 as a primary endpoint. MEDI-7352 is a nerve growth factor and tumour necrosis factor inhibiting-bispecific antibody.

Phase II trial completion

Incyte’s itacitinib saw its PTSR jump in cytokine release syndrome (CRS) after a Phase II trial completion. The PTSR increased by nine points to 60%.

The trial’s status on ClinicalTrials.gov changed from active, not recruiting to completed on 31 August, and GlobalData evaluated the asset the following day.

The Phase II trial (NCT04071366) evaluated the safety and efficacy of oral itacitinib for the prevention of CRS. The study recruited 112 patients who received an approved immune effector cell (IEC) therapy for hematologic malignancies.

Itacitinib is a Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities.

Read the last edition:

Pipeline Moves: Advancement prospects plunge for Bristol-Myers’ oncology drug after trial termination

Need to know:

GlobalData’s proprietary model uses a combination of machine learning and an algorithm to calculate an individual drug’s PTSR and LoA. While LoA provides the probability of a drug ultimately receiving market authorization, PTSR indicates the probability of a drug’s advancement to the next stage of clinical development. The model uses datapoints from individual drugs, clinical trials, regulatory milestones, company, and financial databases.