This week on Pipeline Moves, we start off by looking at the positive topline data from a Phase II trial investigating cardiovascular gene therapy. We continue with negative topline data from a Phase II trial in metabolic disorders and a suspension of an investigator-led Phase II oncology trial. We finish the week on a positive note by reviewing completions of a Phase IIb trial in plaque psoriasis and a Phase I/II trial in glioblastoma multiforme.

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Cardiovascular gene therapy sees positive topline data

XyloCor Therapeutics’s XC001 (encoberminogene rezmadenovec) saw a leap in its Phase Transition Success Rates (PTSR) in coronary artery disease (CAD) and refractory angina after the announcement of positive Phase II topline data. The PTSR increased by 19 points to 45% in CAD and by 16 points to 67% in refractory angina. 

The topline data from the Phase I/II EXACT study (NCT04125732) was announced in a company press release on 26 January, with GlobalData appraising the gene therapy the next day. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

In the press release, the company announced the completion of the Phase II portion of the EXACT trial, which investigated the safety and efficacy of the gene therapy in refractory angina patients. According to the company update, the trial achieved its efficacy and safety objectives. XyloCor is now finalising the design of the pivotal study.

The therapy promotes new blood vessels in the heart, which restores blood flow and potentially reduces chest pain associated with refractory angina.

The six-month data showed no safety issues related to the therapy and no serious adverse events related to XC001’s administration in 28 patients. The therapy reduced ischemic burden, and improved total exercise duration.

Negative Phase II topline data in metabolic disorders

Ocuphire Pharma’s APX-3330 saw a decline in its PTSR after the announcement of negative Phase II topline data. The PTSR decreased by 17 points to 11% in diabetic macular oedema, 18 points to 13% in non-proliferative diabetic retinopathy, and 21 points to 16% in proliferative diabetic retinopathy. The PTSR changes took place on 27 January after a company press release was issued on 25 January.

The randomised, double-masked, placebo-controlled trial (NCT04692688) evaluated the efficacy and safety of APX3330 in diabetic retinopathy patients. According to the press release, the drug was unable to meet its primary endpoint measuring the percentage of subjects with an improvement in Diabetic Retinopathy Severity Score (DRSS).

However, the results from the Phase II trial showed that APX-330 achieved statistical significance on a key pre-specified secondary endpoint, which measured the percentage of patients whose diabetic retinopathy worsened according to their DRSSs. The company hopes that these results will be adequate to plan a new potential Phase III registration endpoint and an end-of-Phase II FDA meeting.

APX-330 is a first-in-class, small molecule, oral inhibitor of the transcription factor regulator Ref-1 (reduction-oxidation effector factor-1). The drug blocks the downstream angiogenesis and inflammation pathways to decrease any abnormal activity associated with diabetic retinopathy and diabetic macular oedema.

Suspension of investigator-led Phase II oncology trial

Exelixis’s Cabometyx (cabozantinib s-malate) saw its PTSR decrease after an investigator-led Phase II trial in melanoma was suspended. The drug’s PTSR declined by 11 points and settled at 25% in melanoma.

The trial’s status was updated from ongoing, recruiting to suspended on ClinicalTrials.gov on 20 January, and GlobalData evaluated the asset on 23 January. The trial was suspended because the futility stage with the first 14 subjects was completed. The study was sponsored by Georgetown University.

The open-label Phase II study (NCT04091750) aimed to evaluate the efficacy and safety of Cabometyx combined with Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) for a 12-week induction period followed by maintenance therapy of Opdivo plus Cabometyx for up to two years in melanoma patients.

The trial recruited 27 adult participants with unresectable stage IIIb-IIId or IV melanoma. The trial’s primary endpoint measured progression-free survival (PFS) within a timeframe of one-year post-treatment. The multiple secondary endpoints measured the incidence of adverse events over a period of two years, overall survival (OS) up to three years and response rate up to one-year post-treatment.

Cabometyx is an anti-neoplastic agent marketed for renal cell carcinoma, thyroid cancer and hepatocellular carcinoma. The asset is a tyrosine kinase inhibitor that blocks the activity of RET, MET, and VEGFR2 as well as other receptor tyrosine kinases, which can be responsible for angiogenesis and oncogenesis.

Phase IIb completion in plaque psoriasis

Protagonist Therapeutics’ PN-235 saw its PTSR rise after a Phase IIb trial completion. The PTSR increased by nine points to 37% in plaque psoriasis. GlobalData evaluated the asset on 19 January after a ClinicalTrials.gov update on 16 January.

The randomised, placebo-controlled, dose-ranging study (NCT05223868) evaluated the safety and efficacy of PN-235. The primary endpoint measured the percentage of participants achieving the Psoriasis Area Severity Index (PASI) 75 Score at week 16. The PASI is used in psoriasis trials to assess and grade the severity of psoriatic lesions and the patient’s response to treatment.

PN-235 is an oral candidate being co-developed by Protagonist Therapeutics and Janssen Biotech. The drug targets the IL-23 pathway. IL-23 is a cytokine that regulates inflammatory and immune function and plays a key role in the development of psoriasis.

Phase I/II glioblastoma multiforme trial completed

Hanmi Pharmaceutical’s HM-21001 saw its PTSR in glioblastoma multiforme increase by ten points to 30% following an investigator-led Phase I/II trial completion. ClinicalTrials.gov updated the trial listing on 18 January, and the PTSR change took effect the following day.

The investigator-initiated, open-label, single-centre Phase I/II trial (NCT04657315) evaluated the maximum tolerated dose, safety, and efficacy of HM-21001 injected into the resection cavity of subjects with recurrent glioblastoma. The trial enrolled 10 patients with recurrent glioblastoma. HM-21001 acts through immunomodulation, self-renewal, and multi-directional differentiation.

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.