This week on Pipeline Moves, we look into the terminations of two oncology clinical trials. We also review the positive data from a Phase II trial in Parkinson’s disease. We finish off with trial completions in autism, liver disease and respiratory failure.
Termination of Phase III lymphoma trial
AbbVie’s and Janssen Biotech’s Imbruvica (ibrutinib) saw its Likelihood of Approval (LoA) decrease in non-Hodgkin lymphoma after a Phase III trial was terminated. The asset’s LoA fell by 11 points to 34%.
The trial’s status was updated on its ClinicalTrials.gov listing on 2 December. GlobalData evaluated the asset on 6 December. GlobalData’s analysis uses a combination of machine learning and its proprietary algorithm. LoA can be calculated for a drug by considering characteristics like therapy area, indication and molecule type.
Janssen terminated the Phase III study (NCT02703272), citing the Independent Data Monitoring Committee (IDMC) recommendation to stop enrolment, as “the EFS hazard ratio and associated p-value crossed the futility boundary specified in protocol”. The randomised, open-label, safety and efficacy trial enrolled paediatric and young adults. A total of 75 subjects were accrued, which was less than the 84 originally anticipated to enrol.
Imbruvica is an inhibitor of Bruton’s Tyrosine Kinase (BTK). The drug is marketed for several oncology indications including chronic lymphocytic leukaemia, Waldenstrom macroglobulinemia, and extradonal marginal zone b-cell lymphoma. Imbruvica is jointly developed and commercialized by AbbVie and Janssen Biotech, a subsidiary of Johnson & Johnson.
Novartis terminates Phase I/II oncology study
Novartis’s BLZ-945 (sotuletinib) saw its Phase Transition Success Rate (PTSR) drop after a Phase I/II trial terminated. The PTSR decreased by 20 points to 15% in pancreatic cancer, 16 points to 8% in solid tumours, and 13 points to 13% in recurrent glioblastoma multiforme (GBM). PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
BLZ-945 was compared to PDR-001 (spartalizumab) which also saw its PTSR drop by 12 points to 11% in GBM and 10 points to 27% in triple-negative breast cancer (TNBC). GlobalData evaluated the assets on 8 December after a ClinicalTrials.gov update the day before.
The open-label and first-in-human trial (NCT02829723) recruited 198 patients with advanced solid tumours. The study aimed to evaluate the safety, efficacy, and anti-tumour activity of BLZ-945 as a single agent or in combination with PDR-001.
BLZ-945 acts as a colony stimulating factor-1 receptor (CSF-1R) antagonist and PDR-001 acts by antagonizing programmed death 1 protein (PD-1).
Positive Phase II data from Parkinson’s trial
BioVie’s NE3107 saw its PTSR rise by 20 points to 47% after the reveal of positive Phase II data from a study featuring patients with Parkinson’s disease. The company shared a press release on 5 December, with GlobalData updating the PTSR the next day.
The 45-patient study examined the pharmacokinetics, safety and tolerability of NE3107 used in combination with carbidopa and levodopa. Carbidopa and levodopa are used for the treatment of symptoms related to Parkinson’s disease.
According to the press release, the study (NCT05083260) met both of its objectives. Specifically, the Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3 motor score of subjects treated with NE3107 and levodopa was three points greater than in patients who were treated solely with levodopa after 28 days at both 2-and 3-hour marks. The release says that this superiority is regarded as clinically meaningful by experts in the indication.
Adding to this, the UPDRS score of patients treated with this combination younger than 70 was roughly six points greater than those on levodopa. 88.9% of patients under 70 treated with both assets reported greater than 30%-part 3 score improvements, two hours post-dose after 28 days of treatment. In contrast, 63.6% of patients on levodopa reported such improvements. 80% of patients on the combination but older than 70 experienced a more than 30% improvement.
The company says that it will proceed with the planning of a potential Phase III trial of NE3107. It will share full data from the Phase II trial at the 2023 International Conference on Alzheimer’s and Parkinson’s disease, which will be hosted in Sweden in March and April.
Completion of Phase II study in autism
Johnson and Johnson’s JNJ-5279 saw a rise in its PTSR by nine points, settling at 43% in autism after the completion of a Phase II trial. The study’s Clinicaltrials.gov listing was updated from active, not recruiting to completed on 8 December. The PTSR change took place on 9 December.
The randomised, double-blind study (NCT03664232) investigated the efficacy, safety, and tolerability of JNJ-42165279 in adolescent and adult participants with autism spectrum disorder. The primary endpoints of the study analysed the changes from baseline for three factors within the Autism Behavior Inventory (ABI).
JNJ-5279 is a non-opioid painkiller underdevelopment for the treatment of generalised anxiety disorder, autism spectrum disorder and neuropathic pain. The drug candidate is a new molecular entity (NME), which acts by inhibiting fatty acid amide hydrolase (FAAH) to reduce chronic stress.
Phase II liver disease trial completed
89bio’s pegozafermin saw its PTSR rise after a Phase II trial in non-alcoholic fatty liver disease (NAFLD) was completed. The PTSR increased by nine points to 36%. GlobalData evaluated the asset on 1 December, following a ClinicalTrials.gov update on the previous day.
The multi-centre Phase II trial (NCT04048135) enrolled 101 patients. The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetic properties of pegozafermin in patients with non-alcoholic steatohepatitis (NASH) or NAFLD and at high risk of NASH.
Pegozafermin is a glycopeglyated fibroblast growth factor 21 (FGF21) analogue, which acts as a FGR1 agonist in the presence of beta klotho. 89bio is developing the subcutaneous drug candidate for the treatment of NASH, NAFLD and severe hypertriglyceridemia.
Completion of Phase II in respiratory failure
Cynata Therapeutics’s CYP-001 saw its PTSR rise by nine points to 43% in respiratory failure, following a Phase II trial completion. The study’s Clinicaltrials.gov listing was updated from recruiting to completed on 28 November. The PTSR change took place on 1 December.
The Covid-19 (Mend) trial (NCT04537351) was a pilot, open-label, randomised controlled Phase I/II study that investigated the early efficacy of CYP-001 in adults admitted to intensive care with respiratory failure. 14 participants were enrolled in the clinical trial.
The primary endpoint of the study was a trend in trajectory of PaO2/FiO2 ratio (P/F ratio) between groups. The P/F ratio is the ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction).
CYP-001 is a mesenchymal stem cell therapy under development for the treatment of steroid-resistant graft versus host disease, respiratory failure and acute respiratory distress syndrome associated with Covid-19. The mesenchymal stem cells function by having an anti-inflammatory effect on the immune system, enhancing tissue regeneration, and protecting cells from damage.