This week on Pipeline Moves, we start the week by looking at two terminations of Phase II trials in pancreatitis and radiation-induced esophagitis. On a positive note, we review trial completions in several oncology indications and psychiatric disorders.
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Regeneron terminates Phase II pancreatitis trial
Regeneron Pharmaceuticals’s Evkeeza (evinacumab) saw its Phase Transition Success Rate (PTSR) fall in pancreatitis after a Phase II trial was terminated. The drug’s PTSR dropped by 10 points to 30% in pancreatitis. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The Phase II trial’s (NCT04863014) status was updated from ongoing, not recruiting to terminated on ClinicalTrials.gov on 22 March, and GlobalData evaluated the asset the following day. The trial was terminated due to the “sponsor decision”.
The objective of the trial was to evaluate the efficacy and safety of Evkeeza in patients with severe hypertriglyceridemia for the prevention of recurrent acute pancreatitis (AP). The trial enrolled 21 patients before the termination. The primary endpoint measured the proportion of patients with at least one positively adjudicated AP episode.
Evkeeza is a monoclonal antibody (mAb) marketed for the adjunct treatment of homozygous familial hypercholesteremia (HoFH). The mAb is under development for the treatment of dyslipidaemia in HoFH, severe forms of hypercholesteremia, and the prevention of acute pancreatitis.
Termination of Phase II esophagitis trial
Galera Therapeutics’s avasopasem manganese (GC4419) saw its PTSR drop after a Phase II trial in esophagitis was terminated. The drug’s PTSR decreased by 32 points reaching 15% in esophagitis.
The trial status was updated from completed to terminated on ClinicalTrials.gov on 14 March. The study was under a quality control review process on ClinicalTrials.gov, which concluded on 22 March, and the asset was evaluated by GlobalData on 24 March. The trial was terminated due to lack of study enrolment.
The open-label, multicentre study (NCT04225026) evaluated the effects of intravenous avasopasem manganese therapy on the incidence and severity of radiation-induced esophagitis in subjects receiving chemoradiotherapy for lung cancer.
The study initially aimed to enrol 60 adult patients with unresectable Stage 3A/3B or post-operative Stage 2B non-small cell lung cancer or small cell lung cancer. However, the trial recruited only 39 participants, according to a ClinicalTrials.gov listing update on 7 June 2022.
Avasopasem manganese is a MnSOD (manganese superoxide dismutase) mimetic, which acts by disrupting tumour metabolism and microenvironment. The drug candidate is also under development for radiation-chemotherapy-induced oral mucositis in head and neck cancer patients.
Completion of Phase I/II oncology trial
TCR2 Therapeutics’s TC-110 saw its PTSR rise in acute lymphocytic leukaemia (ALL) after a Phase I/II trial was completed. The drug’s PTSR increased by six points, reaching 41% in ALL.
The trial status was updated from recruiting to completed on ClinicalTrials.gov on 14 March, and GlobalData evaluated the asset on 17 March.
The open-label study (NCT04323657) evaluated the safety and efficacy of genetically modified TC-110 T-cells combined with fludarabine and cyclophosphamide lymphodepletion regimen in adults with relapsed or refractory Non-Hodgkin lymphoma (NHL) and ALL.
The study initially aimed to recruit 120 participants with histologically confirmed NHL or ALL but ended up recruiting only six subjects. The trial’s primary endpoints measured the recommended Phase II dose based on dose-limiting toxicities (DLTs) within a time frame of 28 days post-treatment, as well as the overall response rate and minimum residual disease within three months following treatment.
TC-110 is composed of T-cells expressing T-cell receptors (TCR) developed based on TRuC-T platform technology. The drug candidate acts by targeting cells expressing CD19, which is a surface antigen which is highly expressed on the surface of tumour cells.
Psychiatric disorder trial completed
Evecxia Therapeutics’s EVX-301 saw its PTSR rise in psychiatric disorders by 13 points to 61% after the completion of a Phase I trial. Evecxia announced the completion of the trial on 15 March, and GlobalData evaluated the asset on 17 March.
The purpose of the single ascending dose, double-blind, placebo-controlled study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics data of EVX-301 in healthy volunteers. 29 subjects received single 24-hour intravascular infusions of EVX-301 (total doses of 1,2 or 3 mg/kg/24 hour) and 10 subjects received a placebo.
EVX-301 is exogenously administered 5-HTP that is converted to serotonin in the brain. EVX-301 is under development for the treatment of acute suicidal ideation and behaviour (ASIB) in patients with MDD responding inadequately to a first-line antidepressant.
Phase I oncology trial completed
Prelude Therapeutics’s PRT-1419 saw its PTSR rise in several cancers after a Phase I trial was completed. The PTSR increased by eight points to reach 62% in both cervical cancer and small-cell lung cancer, and 59% in melanoma, oesophageal cancer, and head and neck cancer. The PTSR also rose by eight points to land at 60% in sarcomas, and 37% in solid tumours.
On 15 March, the trial’s status was updated to completed on ClinicalTrials.gov, and GlobalData evaluated the asset the following day. The purpose of the open-label, multi-centre, dose-escalation Phase I trial (NCT04837677) was to define the dosing schedule, the maximum tolerated dose and/or estimate the optimal biological dose to be used in the subsequent development of PRT-1419. The trial enrolled 26 patients with advanced solid tumours.
PRT-1419 is under development for the treatment of various cancers. The drug candidate acts as a highly selective and reversible MCL-1 inhibitor.
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.