This week on Pipeline Moves, the team looks into a Phase II trial in essential tremor, as well as one in glioblastoma multiforme (GBM). We also feature a Phase II trial in open-angle glaucoma, plus a Phase III trial in chronic urticaria (hives).
Phase II essential tremor trial completes
Neurocrine Bioscience’s NBI-827104 saw its Phase Transition Success Rate (PTSR) in essential tremor rise following the completion of a Phase II study. The PTSR increased by nine points, reaching 24%.
The trial’s completed status was updated on its ClinicalTrials.gov listing on July 12, with GlobalData evaluating the asset the next day. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The placebo-controlled Phase II crossover study (NCT04880616) initially aimed to recruit 20 patients but completed with 31 subjects. The study’s primary outcome measure is postural tremor changes at day 28 of each treatment period.
Oral NBI-827104 acts by inhibiting T-type calcium channels, which in turn block the calcium-dependent release of multiple neurotransmitters. Essential tremor is a neurological disorder that causes involuntary and rhythmic shaking. NBI-827104 is also under development in epilepsy and epileptic encephalopathy.
Phase II GBM trial completes
Merck KGaA’s Bavencio (avelumab) saw its PTSR in GBM jump nine points to 38% following the completion of an investigator-led Phase II trial. ClinicalTrials.gov updated the trial’s status from active, not recruiting to completed on July 21, and the PTSR change took effect the next day.
The 30-patient Phase II study (NCT03047473) tested Bavencio, alongside SOC temozolomide and radiotherapy, in patients newly diagnosed with GBM. The study was sponsored by Clinique Neuro-Outaouais. As a primary endpoint, the trial assessed the number of treatment-emergent adverse events leading to Bavencio interruption or termination over 52 weeks. The secondary endpoint was radiological tumour response according to the immunotherapy Response Assessment for Neuro-Oncology (iRANO).
Bavencio is a checkpoint inhibitor that blocks the protein programmed death-ligand 1 (PD-L1). The monoclonal antibody is marketed for treating Merkel cell carcinoma, metastatic renal cell carcinoma, and metastatic transitional tract cancer.
Betaliq Phase II trial completes
Betaliq’s BTQ-1901 (nebivolol) saw its PTSR in open-angle glaucoma rise following the completion of a Phase II study. The PTSR grew by eight points to 39%. The Phase II trial’s (NCT04910100) status on ClinicalTrials.gov changed from recruiting to completed on July 20, with GlobalData assessing the candidate a day later.
The Phase II recruited patients with open-angle glaucoma or ocular hypertension. The trial investigated two doses of the ophthalmic suspension nebivolol (1% and 0.5%), as well as one dose of an ophthalmic suspension of BTQ-1902 (timolol) (0.5%). It lists an ophthalmic solution of timolol (0.5%) as an active comparator. Participants are divided among these four arms, to be dosed twice daily to both eyes for 84 days.
The trial had a primary endpoint measuring intraocular pressure over 84 days. The study aimed to enrol 240 participants but closed with 225. Nebivolol antagonises the beta-1 adrenergic receptor, while Timolol targets both beta-1 and -2 and adrenergic receptors.
Novartis completes trial in hives
Novartis’s dermatology asset QGE031 (ligelizumab) saw its Likelihood of Approval (LoA) increase in hives after a Phase III trial was completed. The LoA went up six points to 55%. GlobalData appraised the asset on July 18 after a ClinicalTrials.gov update on July 15.
The open-label, single-arm, Japan-based Phase III trial (NCT03907878) enroled 66 adult subjects with chronic hives who remain symptomatic despite H1-antihistamines treatment. The trial’s primary endpoint investigated QGE031’s safety profile, with changes in the Urticaria Activity Score (UAS) as a notable secondary endpoint. The trial measured UAS every four weeks within a 64-week time frame. UAS is the sum of Hive Severity Score (HSS) and Itch Severity Score (ISS).
QGE031 is an anti-immunoglobulin E (IgE) antibody which was granted a Breakthrough Therapy Designation in January 2021. In December 2021, Novartis announced that QGE031 showed superiority compared to placebo at week 12, but not against Novartis’s Xolair (omalizumab) in twin Phase III studies PEARL 1 (NCT03580369) and PEARL 2 (NCT03580356). Full data in these two trials will be released after study completion in H2 2022. The asset is also under investigation in a Phase III food and peanut allergy study (NCT04984876).
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 data points from the individual drugs, clinical trials, regulatory milestones, company, and financial databases.