This week on Pipeline Moves, we start off by looking at two Phase III trial terminations in colorectal and bladder cancers. We continue by investigating the trial terminations in glycogen storage disease and several oncology indications. We finish the week on a positive note by reviewing a Phase II trial completion in cardiomyopathy.
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By GlobalDataPhase III colorectal cancer trial terminated
G1 Therapeutics’s Cosela (trilaciclib) saw its Likelihood of Approval (LoA) plunge after a Phase III oncology trial was terminated. The LoA dropped by 33 points to 17% in metastatic colorectal cancer (mCRC).
GlobalData evaluated the asset on 10 April, after a ClinicalTrials.gov update on 7 April. 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.
Even though Cosela achieved co-primary endpoints and other secondary measures of myeloprotection and tolerability, G1 decided to terminate the trial due to the low likelihood of achieving progression-free survival and overall survival endpoints.
The double-blinded, placebo-controlled trial (NCT04607668) enrolled 326 patients with mCRC receiving chemotherapy and bevacizumab. Cosela, a CDK4/6 inhibitor, was marketed by the FDA as a treatment for chemotherapy induced myelosuppression in 2021.
Termination of Phase III bladder cancer trial
UroGen Pharma’s VesiGel (UGN-102) saw its LoA drop after a Phase III trial in non-muscle invasive bladder cancer (NMIBC) was terminated. The drug’s LoA decreased by five points to 27%.
As per ClinicalTrials.gov, the trial was terminated because the company chose to pursue an alternate approach. The trial status was updated from recruiting to terminated on ClinicalTrials.gov on 3 April, and GlobalData evaluated the asset on the following day.
The open-label trial (NCT04688931) evaluated the efficacy, durability, and safety of VesiGel in patients with NMIBC. The trial recruited only 282 out of the 632 patients originally anticipated to participate.
VesiGel, a sustained release formulation of high dose mitomycin C, is under development for the treatment of low-grade intermediate NMIBC. The small molecule drug candidate acts as a DNA synthesis inhibitor. Vesigel is also under investigation in a separate single-arm Phase III NMIBC study (NCT05243550), with a trial completion date of February 2028.
Phase I/II study in rare metabolic disease terminated
Ultragenyx Pharmaceuticals’s UX053 saw its Phase Transition Success Rate (PTSR) fall in glycogen storage disease type III (GSD III) after a Phase I/II trial was terminated. The drug’s PTSR dropped by 16 points to 11%. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The Phase I/II trial’s (NCT04990388) status was updated from ongoing, not recruiting to terminated on ClinicalTrials.gov on 4 April, and GlobalData evaluated the asset the following day. The trial was terminated due to a sponsor decision that was unrelated to the drug’s safety.
The objective of the trial was to evaluate the efficacy, safety, tolerability, and pharmacokinetics of a single-ascending dose and repeat doses of UX053 in patients with GSD III. UX053 is an mRNA therapy that codes for glycogen debrancher enzyme (AGL). UX053 is designed to replace AGL, which is deficient in GSD III.
Pfizer terminates Phase I trial in oncology vaccine
Pfizer’s cancer vaccine candidate PF-07263689 saw its PTSR plummet in three oncology indications after a Phase I trial was terminated. The PTSR fell by 25 points to 32% in colorectal cancer, 26 points to 33% in renal cell carcinoma, and 25 points to 31% in melanoma.
The trial’s ClinicalTrials.gov listing was updated from active, not recruiting to terminated on 3 April, with the sponsor citing a “business decision that was not due to safety concerns with PF-07263689”.
The dose escalation and expansion trial (NCT05061537) was testing PF-07263689 both alone and in combination with Pfizer’s anti-programmed cell death protein 1 (PD-1) antibody sasanlimab. As primary endpoints, the 13-subject Phase I study assessed the safety, dose-limiting toxicities, and pharmacodynamics of PF-07263689 with and without sasanlimab.
PF-07263689 is an oncolytic virus designed to release tumour antigens causing the immune system to recognize and act against them. Sasanlimab is also in development in a Phase III trial (NCT04165317) for non-muscle invasive bladder cancer as well as in multiple Phase I and II studies in other oncology indications including non-small cell lung cancer and solid tumours.
Termination of Phase I lymphoma trial
Roche’s tiragolumab saw its PTSR drop in non-Hodgkin lymphoma (NHL) after a Phase I trial was terminated due to slow recruitment. Tiragolumab is being developed by trial sponsor Genentech, a division of the Roche group.
The drug’s PTSR dropped by 45 points to 21%. The trial status was updated from recruiting to terminated on ClinicalTrials.gov on 7 April, and GlobalData evaluated the asset the following day.
The objective of the trial (NCT04045028) was to evaluate the efficacy, safety, tolerability, pharmacodynamics, preliminary activity, and pharmacokinetics of tiragolumab alone or in combination with certain therapies in participants with relapsed or refractory NHL or multiple myeloma (MM).
The trial was evaluating tiragolumab with Roche’s Tecentriq (atezolizumab) and/or Janssen Oncology’s, a part of Johnson and Johnson, Darzalex (daratumumab) or Rituxan (rituximab), which is marketed by Biogen and Genentech.
Tiragolumab is a monoclonal antibody (mAb) that binds to the T cell immunoglobulin and ITIM domain protein. The mAb is under development for the treatment of various cancers.
Phase II cardiovascular trial completed
Berlin Cures’s BC-007 saw its PTSR in dilated cardiomyopathy rise nine points to 38% following the completion of a Phase II trial. The ClinicalTrials.gov updated the trial listing from active, not recruiting to completed on 3 April, and the PTSR change took effect the following day.
The 30-subject, placebo-controlled study (NCT04192214) tested BC-007’s ability to neutralize autoantibodies directed against the beta1 adrenergic receptor (β1 AAb) over 12 months. β1 AAb is associated with the development of dilated cardiomyopathy and associated chronic heart failure. BC-007 is a DNA aptamer that binds to β1 AAb and is administered via infusion.
The study’s primary endpoint is the proportion of β1 AAb-negative participants after 12 months, and secondary endpoints include measures of safety, tolerability, and pharmacokinetics. An exploratory efficacy endpoint is evaluating the change of the left ventricular ejection fraction (LVEF) after BC-007 dosing.
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.
