GSK cancer drug takes a hit in four indications: regulatory roundup
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Regulatory roundup: GSK’s Zejula hampered by Phase II suspension

By Reynald Castaneda 04 Oct 2021 (Last Updated October 5th, 2021 16:17)

BMS’s and Cytokinetics’ respective CVD drugs are among other assets reviewed by GlobalData’s Investigative News team.

Regulatory roundup: GSK’s Zejula hampered by Phase II suspension
A University of Florida-sponsored Phase II study of GlaxoSmithKline’s Zejula (niraparib) lead to the drug’s PTSR to dive across four oncological indications following the study’s suspension. Credit: Willy Barton / Shutterstock.com

Need to Know:

GlobalData’s proprietary model uses a combination of machine learning and an algorithm to calculate an individual drug’s Phase Transition Success Rate (PTSR) and Likelihood of Approval (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 data points from the individual drugs, clinical trials, regulatory milestones, company, and financial databases.

Keytruda combo pancreatic cancer trial shuttered

Merck’s Keytruda (pembrolizumab) saw its PTSR in advanced pancreatic cancer dip 11 points to 33% after its Phase II combination trial with Oncolytics Biotech’s Reolysin (pelareorep) was terminated. Reolysin is a virus-based therapy for solid tumours and hematological malignancies.

The Phase II trial (NCT03723915) of Keytruda plus Reolysin was terminated after it failed to meet its accrual goal of 34 patients, according to ClinicalTrials.gov. The first stage of the study did not meet the interim analysis criteria to move to Stage 2 of the Simon two-stage design. The PTSR change occurred on 22 September after the update was posted on ClinicalTrials.gov on 21 September.

The trial termination also resulted in a three-point fall to the drug’s LoA, which dropped to 9%. The trial was sponsored by Northwestern University and run in collaboration with the National Cancer Institute.

Zejula takes a hit in four cancer indications

A University of Florida-sponsored Phase II study of GlaxoSmithKline’s Zejula (niraparib) lead to the drug’s PTSR to dive across four oncological indications following the study’s suspension. The PTSR fell by 11 points to 25% in bile duct cancer and renal cell carcinoma, six points to 31% in malignant mesothelioma and 13 points to 14% in uveal melanoma.

The 57-subject, open-label Phase II trial (NCT03207347) was suspended as per a 28 September update on ClinicalTrials.gov. The PTSR update happened the same day. Recruitment has been suspended on the grounds of waiting for subject availability for an interim analysis. The primary outcome had sought the objective response rate (ORR) for subjects with BAP1 DNA double-strand mutations over a one-year timeframe.

The study also saw a similar decrease in the candidate’s LoA across all four indications. The LoA dropped by three points to 8% in bile duct cancer, five points to 10% in renal cell carcinoma, two points in malignant mesothelioma and by one point to 1% in uveal melanoma.

BMS asset in congestive heart failure dampened

The prospects for Bristol Myers Squibb’s BMS-986259 to advance as a treatment for congestive heart failure dampened by 10 points after its Phase II study was completed. The drug’s PTSR dropped to 10% after the study was closed after recruiting fewer patients than anticipated.

The Phase II study (NCT04318093) was designed to evaluate BMS-986259 in stabilised patients hospitalised for acute decompensated heart failure. While the trial was initially meant to enrol 72 participants, it was completed having accrued only 25. The study’s status was updated on ClinicalTrials.gov on 21 September, but no results have been posted yet.

In addition to the PTSR change, which occurred on 25 September, the drug’s LoA also dropped by three points to 6%.

Cytokinetics’ CVD asset transition chances bolstered

Cytokinetics’ cardiovascular drug CK-3773274 (aficamten) had its PTSR in hypertrophic cardiomyopathy bounce by 16 points to 57% after having its Phase II trial results announced. The completed Phase II randomised, double-blind study (NCT04219826) had its results published in a company press release on 12 September.

The study examined the impact of aficamten on 48 enrolled subjects with hypertrophic cardiomyopathy. Measuring the concentration-response relationship of aficamten on the resting left ventricular outflow tract gradient (LVOT-G) on echocardiogram over a timeframe of 10 weeks, participants saw their baseline levels drop. Split into two cohorts, 78.6% of the first cohort have seen their resting gradient drop to <30 mmHg, with 92.9% of the second cohort seeing a similar drop. In contrast, only 7.7% in the placebo group had a similar drop by week 10.

The study also saw the candidate’s LoA grow by one point to 4%. Both PTSR and LoA were updated on 28 September.

Adaptimmune cancer asset buoyed by trial initiation

Adaptimmune Therapeutics’ Phase II asset ADPA-2M4CD8 saw its PTSR in oesophageal cancer and gastroesophageal (GE) junction carcinomas rise by five and 12 points, respectively, due to a trial initiation and other updates. The PTSR in oesophageal cancer currently stands at 24%, which had increased by five points. In the case of gastroesophageal junction carcinomas, the PTSR sits at 33%, which jumped 12 points.

The Phase II open-label clinical trial (NCT04752358) began enrolment as per a 24 September update on ClinicalTrials.gov. The trial completion date was changed from February to April 2023. The PTSR was updated on 27 September.

The trial has 45 subjects with advanced oesophageal or gastroesophageal junction cancers. The study primary outcome measures the overall response rate (ORR) over a time frame of 2.5 years.

The trial also saw an increase in the asset’s LoA, rising by one point to 7% for oesophageal cancer and by six points to 17% for gastroesophageal junction carcinomas.

Oramed reports Phase II NASH trial data

Oramed Pharmaceuticals’ human insulin saw its PTSR in nonalcoholic steatohepatitis (NASH) jump by 16 points to 49% following Phase II trial results. The completed Phase II study (NCT02653300) had its results posted in a 23 September update on ClinicalTrials.gov.

The study examined the effect of human insulin on reducing liver fat content in 10 enrolled subjects suffering from NASH, eight of whom have completed it. Measuring the change in MRI-Proton Density Fat Fraction (MRI-PDFF) as the primary outcome, eight participants had their MRI-PDFF fall from 21.3% to 14.4% after they were administered human insulin orally. The MRI-PDFF was measured on a 12-week timeframe.

The study also saw the candidate’s LoA grow by two points to 6%. The PTSR and LoA was updated on 27 September.

EmeraMed builds momentum in rare disease

EmeraMed’s emeramide saw its PTSR in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) rise by nine points each after a Phase II trial was completed. The PTSR in PSP currently sits at 27% while that in MSA is now 56%. PSP and MSA are both atypical forms of Parkinson’s disease.

The Phase II placebo-controlled crossover study (NCT04184063) evaluating the drug’s effect on symptoms and health-related quality of life over 28 days enrolled 20 patients with PSP or MSA. Emermaide, also known as NBMI, is an oral isophthalamide derivative that can prevent oxidative damage and reduce disease toxicity.

The study completion, which was posted to ClinicalTrials.gov on 23 September, resulted in a modest one-point bump to the drug’s LoA in MSA to 2%, but there was no LoA change in PSP, which remained at 1%. EmeraMed is headquartered in Ireland and also operates in the US and Sweden.