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September 13, 2022

Pipeline Moves: Trial completions in Duchenne muscular dystrophy and chronic urticaria

The Clinical Trials Arena team also investigates missed endpoints in wound infections, and terminations in head and neck cancer and liver cancer.

By Clinical Trials Arena Team

This week on Pipeline Moves, we look into the completion of a Phase I trial in Duchenne muscular dystrophy (DMD), alongside completion of Phase IIa in chronic urticaria. We analyse the missed primary endpoint in Phase III surgical wound infections trial. Finally, we feature terminations of investigator-led Phase II study in head and neck cancer squamous cell carcinoma and Phase III in hepatocellular carcinoma.

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Duchenne Phase I trial completed

Edgewise Therapeutics’s EDG-5506 saw its Phase Transition Success Rate (PTSR) jump seven points to 66% in Duchenne muscular dystrophy (DMD) following the completion of a Phase I trial.

ClinicalTrials.gov updated the study’s listing from enrolling by invitation to completed on 2 September, and the PTSR change took effect on 5 September. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The Phase I study (NCT05492734) compared EDG-5506 concentrations in venous and capillary blood samplings in ten healthy volunteers. Primary outcome measures included the difference in area under the concentration-time curve, plasma maximum drug concentration, and time of maximum concentration.

DMD is a rare genetic disorder characterised by progressive muscle degeneration, occurring most commonly in young boys. EDG-5506 is a small molecule designed to modulate the skeletal muscle motor protein myosin, preventing muscle breakdown.

Missed endpoint in Phase III surgical wound infections

PolyPid’s D-PLEX (doxycycline hyclate) saw its Likelihood of Approval (LoA) drop in surgical wound infections after a Phase III trial did not achieve its primary endpoint of reduction in surgical site infections and mortality. The LoA decreased by 16 points to 21%.

GlobalData evaluated the asset on 6 September after a 2 September company press release announced the results. LoA is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm.

The two-arm, double-blind Phase III trial (NCT04233424) had planned to enrol 1,116 patients undergoing elective colorectal surgery involving resection. The trial accrued 977 patients, according to the press release. D-PLEX was administered in combination with standard of care (SoC) in 488 patients compared to SoC alone in 489 participants.

The primary outcome measures anti-infective efficacy of the asset over a period of 30 days post operation. The trial was designed to demonstrate at least a 50% reduction in surgical site infections (SSIs).

The topline results show a 23% decrease in the prevention of SSIs and mortality compared to the SoC control arm. There were 15 deaths in the SoC arm and 11 deaths in the treatment arm in the first 30 days after surgery. The treatment arm also did not achieve statistical significance on the key secondary endpoint measuring SSIs within 30 days post-abdominal index surgery. In a pre-specified subgroup analysis requested by the FDA of subjects with incision lengths >20 cm, the local administration of D-PLEX100 resulted in a statistically significant reduction of 54% on the primary endpoint, compared to SoC alone.

D-PLEX is administered by topical route and elicits anti-bacterial properties. The asset received Breakthrough Therapy designation in 2020.

Investigator-led Phase II head and neck cancer trial terminates

Oncosec Medical’s TAVO (tavokinogene telseplasmid) saw its PTSR in head and neck cancer squamous cell carcinoma dive by 14 points to 15% after the termination of a Phase II study.

The trial’s status on ClinicalTrials.gov changed from active, not recruiting to terminated on 6 September. The trial was terminated due to the treatment (being) ineffective as per the ClinicalTrials.gov entry. GlobalData appraised the asset on 7 September. The trial was sponsored by Dr Chase Heaton, associate professor from the University of California, San Francisco.

The open-label study (NCT03823131) investigated the use of tavokinogene telseplasmid with electroporation (TAVO-EP), Merck’s Keytruda (pembrolizumab), and epacadostat work in subjects with head and neck squamous cell carcinoma. The primary endpoint for the 14-subject trial featured was best overall response rate.

Tavokinogene telseplasmid is an interleukin-12 alpha and beta activator, which stimulates the production of interferon-gamma and inhibits tumour angiogenesis.

Completion of Phase IIa chronic urticaria trial

Leo Pharma’s LEO-152020 saw its PTSR in chronic urticaria jump by nine points to 40% after the completion of a Phase IIa trial. The study’s status changed from recruiting to completed as per a 2 September update on its ClinicalTrials.gov listing. GlobalData appraised the asset on 5 September.

Leo Pharma is a private Danish company and a subsidiary of the Leo Foundation. LEO-152020 is an oral histamine receptor 4 (H4R) antagonist that reduces the secretion of proinflammatory proteins and peptides such as cytokines. It is also being studied in atopic dermatitis or eczema.

The double-masked study (NCT04853992) investigated the efficacy and safety of LEO-152020 in adult subjects with cholinergic urticaria. Urticaria is more commonly known as hives. The study measured the change from baseline in post-provocation Urticaria Activity Score after a seven-day treatment course. It also tracked the number of treatment-emergent adverse events per subject from the start of treatment until three days after its end. The study was expected to recruit 28 subjects but enrolled 20.

Phase III in hepatocellular carcinoma terminates

Jiangsu Hengrui Medicine’s Airuika (camrelizumab) saw its LoA drop in hepatocellular carcinoma after a Phase III trial was terminated due to sponsor’s R&D strategy adjustment. The LoA decreased by seven points to 31%. GlobalData evaluated the asset on 2 September after a ClinicalTrials.gov update the day before.

The randomised, open-label trial (NCT04985136) anticipated to recruit 482 patients with advanced hepatocellular carcinoma with no more than two previous lines of treatment. One subject was recruited before termination. The study intended to investigate the efficacy and safety of Airuika in combination with Aitan (rivoceranib mesylate) versus investigator’s choice of regimen. Primary endpoints measured objective response rate (ORR) and overall survival (OS) at 2.5 years.

Airuika is a monoclonal antibody that binds programmed cell death protein (PD-1), resulting in inhibition of downstream signalling pathways that prevent the immune system from killing cancer cells. Airuika was marketed for oesophageal squamous cell carcinoma, Hodgkin lymphoma, metastatic hepatocellular carcinoma, nasopharyngeal cancer, non-small cell lung cancer in 2019.

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.

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