This week on Pipeline Moves, we look at the recent completion of a Phase I/II trial investigating AstraZeneca’s Imfinzi in several oncology indications. We also review the terminations of Phase I/II oncology and Phase II Gaucher disease trials. We finish off with the completions of Phase II trials in kidney and bacterial infectious diseases, as well as a Phase I/II study completion in diabetic eye disease.
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By GlobalDataCompletion of Phase I/II oncology trial
AstraZeneca’s Imfinzi (durvalumab) saw its Phase Transition Success Rate (PTSR) increase in three oncology indications after a Phase I/II trial completion. The PTSR increased by nine points in non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, and Hodgkin’s lymphoma to 43%, 38% and 34%, respectively.
ClinicalTrials.gov updated the trial listing on 10 January, and the PTSR change took effect on the following day. The trial was sponsored by Celgene, a subsidiary of Bristol Myers Squibb (BMS). PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The open-label, multi-centre Phase I/II trial (NCT02733042) assessed the safety and tolerability of Imfinzi as a monotherapy or in combination with Teva Pharmaceuticals’s Bendeka (bendamustine), BMS’ Revlimid (lenalidomide), Rituxan (rituximab) marketed by Biogen and Genentech, and Imbruvica (ibrutinib) marketed by AbbVie and Janssen.
The trial enrolled 106 patients with lymphoma or chronic lymphocytic leukaemia, a significant decrease compared to the original target of 253 patients. The results of the trial concluded that Imfinzi was well tolerated as a monotherapy and combination therapy but should be closely monitored.
Imfinzi is a programmed death-ligand 1 (PD-L1) blocking antibody marketed and under development by AstraZeneca for several cancers.
Phase I/II oncology trial terminated due to product discontinuation
Roche’s LY-2940680 (taladegib) saw its PTSR decline following an institution-led Phase I/II trial termination in oesophageal and gastroesophageal junction cancer. The drug’s PTSR decreased by 21 points in oesophageal cancer and by 27 points in adenocarcinoma of the gastroesophageal junction, settling at 12% and 21% respectively.
The trial’s status was updated on ClinicalTrials.gov from completed to terminated on 16 January and GlobalData evaluated the asset on 18 January. The study was terminated due to product discontinuation. The trial was sponsored by M.D. Anderson Cancer Center in collaboration with National Cancer Institute.
The open-label Phase I/II trial (NCT02530437) evaluated the efficacy and safety of LY-2940680 administered orally daily concurrently with weekly Bristol-Myers Squibb’s Taxol (paclitaxel), Paraplatin (carboplatin) and radiation therapy in patients with adenocarcinoma of the oesophagus or gastroesophageal junction.
The study recruited seven adult participants diagnosed with localised nuclear glioma-associated oncogene homolog (Gli-1) expressing adenocarcinoma of the oesophagus or gastroesophageal junction. The study’s co-primary endpoints aimed to assess the dose-limiting toxicities and the pathologic complete response rate of LY-2940680 in combination with Taxol, Paraplatin and radiation therapy.
LY-2940680 is an SMO (smoothened) inhibitor which acts by binding to the human SMO transmembrane receptor and blocking Shh-induced Gli1 expression. The inhibition of this signalling pathway is important for the suppression of cancer growth, invasion, and metastasis.
Phase II Gaucher disease trial terminated
Orphazyme’s arimoclomol saw its PTSR drop after a Phase II trial was terminated because the Covid-19 pandemic made it impossible to assess the trial objective, according to the trial listing on ClinicalTrials.gov. The PTSR decreased by 21 points in Gaucher disease Type I and by 22 points in Gaucher disease Type III, settling at 19% in both indications.
GlobalData evaluated the asset on 12 January after a ClinicalTrials.gov update the day before. Orphazyme is a subsidiary of KemPharm, which sponsored the study.
The multi-centre, double-blinded, placebo-controlled trial (NCT03746587) recruited 39 participants with Gaucher disease Type I or Type III. The study aimed to evaluate the response of three dose levels of arimoclomol on various pharmacodynamic biomarkers in blood and cerebrospinal fluid.
Gaucher disease is a rare genetic disorder causing the build-up of fat-laden Gaucher cells in the spleen, liver and bone marrow. Arimoclomol acts by causing the up-regulation of molecular chaperones in cells and targets the heat-shock protein 70.
Completion of Phase II kidney disease study
Boehringer Ingelheim’s BI-685509 saw its PTSR in diabetic nephropathy increase by nine points to 34% following a Phase II trial completion. ClinicalTrials.gov updated the trial listing on 11 January, and the PTSR change took effect the following day.
The randomised, double-blinded, placebo-controlled, parallel-group Phase II trial (NCT04750577) investigated the effects of different doses of oral BI-685509 in patients with diabetic kidney disease. The trial enrolled 243 patients.
BI-685509 is a guanylate cyclase activator under development for the treatment of clinically significant portal hypertension, cirrhosis, diabetic nephropathy, adults with early progressive diffuse cutaneous systemic sclerosis and chronic kidney disease.
Anthrax vaccine completes Phase II
GC Biopharma’s vaccine GC-1109 saw its PTSR in anthrax increase by 15 points to 59% following a Phase II trial completion. ClinicalTrials.gov updated the trial listing on 4 January, and the PTSR change took effect on 6 January.
The Phase II trial (NCT01624532) assessed the safety, efficacy, and dose response of GC-1109 in healthy subjects. The primary objectives of the trial were to investigate the optimum volume of the vaccine candidate and evaluate if GC-1109’s Toxin Neutralization Antibody meets the NF50 standard by Toxin Neuralization Antibody (TNA assay) at four weeks after being administered three times. The trial enrolled 240 patients, while the original target was 299 patients.
GC-1109 is an anti-protective antigen (PA) antibody and acts as a prophylactic anthrax vaccine. South Korea’s GC Biopharma is developing the intramuscularly administered vaccine candidate for the prevention of anthrax.
Phase I/II study in diabetic eye disease completed
Exonate’s EXN407 saw its PTSR rise after a Phase I/II trial was completed. The PTSR increased by 10 points to 34% in diabetic macular oedema (DMO). GlobalData evaluated the asset on 11 January after a ClinicalTrials.gov update the day before.
The first-in-human, double-masked, dose-escalation study (NCT04565756) recruited 48 patients with centre involved DMO. The trial evaluated the safety and tolerability of EXN407 as primary endpoints. EXN-407 acts by inhibiting serine/threonine-protein kinase (SRPK1). DMO is the accumulation of excess fluid in the extracellular space within the retina in the macular area.
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.
