This week on Pipeline Moves, we kickoff by looking at the terminations of a Phase II trial in hearing disorders, two Phase I/II trials in metastatic uveal melanoma and diffuse large B-cell lymphoma, and a Phase I trial in systemic lupus erythematosus. We also examine the completion of a Phase III trial in amyotrophic lateral sclerosis. On a good note, we investigate the completion of a Phase II trial in colorectal cancer.

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Phase II trial termination

Gateway Biotechnology’s zonisamide saw its Phase Transition Success Rate (PTSR) drop in hearing disorders after an investigator-led Phase II trial was terminated. The drug’s PTSR fell by 12 points to 12%. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The Phase II trial (NCT04768569) was sponsored by the Washington University School of Medicine. The trial’s status was updated from recruiting to terminated on ClinicalTrials.gov on 6 October, and GlobalData evaluated the asset on 9 October. According to the study’s ClinicalTrials.gov listing, the study was terminated due to undisclosed reasons by the Department of Defense (DoD).

The study assessed the safety and efficacy of zonisamide for the treatment of noise-induced hearing loss. The trial enrolled 24 patients.

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By GlobalData

Zonisamide acts as a voltage-dependent T type calcium channel blocker. The drug candidate is under development by the St Louis, Missouri-based company for the treatment of noise-induced hearing loss.

Termination of Phase I/II trial

Bellicum Pharmaceuticals’s BPX-701 saw its PTSR drop in metastatic uveal melanoma after a Phase I/II trial was terminated. The PTSR decreased by 20 points to 8%.

The trial’s (NCT02743611) status was updated from active, not recruiting to terminated on 5 October, with GlobalData evaluating the asset the following day.

According to the ClinicalTrials.gov registry, the trial was terminated due to a company decision.

The Phase I/II dose-finding trial evaluated the safety, feasibility and activity of BPX-701 in patients with acute myeloid leukaemia (AML) or metastatic uveal melanoma. The study enrolled four out of the estimated 28 participants before the termination.

BPX-701 is a controllable PRAME T-Cell receptor therapy that elicits anti-neoplastic activity.

Phase I/II trial termination

Philogen SpA’s darleukin saw its PTSR fall in diffuse large B-cell lymphoma after a sponsor-led Phase I/II trial was terminated. Darleukin’s PTSR dropped by 15 points to 12%.

The trial’s status on ClinicalTrials.gov was changed from active, not recruiting to terminated on 6 October. GlobalData evaluated the asset on 9 October. The company said the trial was terminated because of slow progression due to difficulties in finding eligible patients adding that competitive clinical trials with innovative agents and new approved products lead to a definitive stop.

The Phase I/II open-label, multicentre, prospective study (NCT02957019) enrolled six patients. The study was to investigate the safety and dose level of darleukin in combination with rituximab in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Darleukin is under development for the treatment of metastatic melanoma and stage III and IV unresectable melanoma patients. The drug candidate is administered by intravenous and intratumoural routes.

Novartis Phase I trial termination

Novartis’s PTSR for pipeline drug MHS-552 has more than halved for systemic lupus erythematosus after the company terminated a Phase I trial.

The PTSR fell by 24 points to 21% in systemic lupus erythematosus as a result of the termination.

The Phase I trial’s status was updated from active, not recruiting to terminated on ClinicalTrials.gov on 26 September. The reason for the termination has not been reported but it has been confirmed that it was a sponsor decision. GlobalData evaluated the asset on 29 September.

It is also reported that the randomised, placebo-controlled, participant- and investigator- blinded, two-part non-confirmatory multiple ascending dose (MAD) trial (NCT05203419) was planned to be conducted in two parts but the study was terminated before Part B was initiated. The study had enrolled eight patients, much lower than the anticipated 28.

Increased approval prospects in Phase III trial

Seelos Therapeutics’s  Cabeletta (trehalose) saw its Likelihood of Approval (LoA) increase in amyotrophic lateral sclerosis after the completion of a Phase III trial. The LoA grew by four points to 16%.

LoA is identified via GlobalData’s analysis using a combination of machine learning and a proprietary algorithm. LoA can be calculated for a drug by considering characteristics like therapy area, indication and molecule type.

The trial’s status (NCT05136885) was updated from recruiting to completed on ClinicalTrials.gov on 4 October, and GlobalData evaluated the asset on the following day.

The purpose of the multi-centre, multi-regimen study was to evaluate the safety and efficacy of investigational products for the treatment of amyotrophic lateral sclerosis. The trial enrolled 161 patients.

Cabletta reduces the aggregate formation of mutant PABPN1. The drug candidate is under development for the treatment of oculopharyngeal muscular dystrophy (a type of congenital myopathy), Huntington’s disease (HD), Friedreich ataxia, Amyotrophic lateral sclerosis, Sanfilippo syndrome and undisclosed liver disease.

Phase II trial completion

TRACON Pharmaceuticals’s methoxyamine hydrochloride saw a 10-point jump in its PTSR in colorectal cancer, landing at 32% following an investigator-led Phase II trial completion.

The Phase II study’s (NCT01851369) Clinicaltrials.gov status was updated from recruiting to completed on 5 October, and GlobalData evaluated the asset on 9 October.

The Phase II trial was led by the National Cancer Institute. The study investigated the safety and effectiveness of the therapy in combination with temozolomide in patients with relapsed solid tumours and lymphomas. The primary endpoints of the trial were to measure the response rate to the combination, the safety, tolerability, and maximum tolerated dose, and the pharmacokinetic (PK) profile of oral methoxyamine hydrochloride.

Methoxyamine hydrochloride is a DNA repair inhibitor that acts by covalently binding to apurinic/apyrimidinic (AP) DNA damage sites and inhibiting base excision repair. This causes an increase in DNA strand breaks and apoptosis, preventing cancer cells from repairing themselves. The treatment is also being developed for several other cancers such as non-small cell lung cancer, ovarian cancer and malignant mesothelioma.

Read the last edition:

Pipeline Moves: Advancement prospects plunge for myelodysplastic syndrome drug after trial termination

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.