This week on Pipeline Moves, we kick off by looking at a Phase II trial termination by Novartis after it shares concerns about the benefit-risk ratio of its amyotrophic lateral sclerosis candidate.
Meanwhile, SonALASense has terminated a Phase I/II trial of its recurrent glioblastoma multiforme candidate and Orca Biosystems terminated a Phase I trial of its graft versus host disease drug.
Go deeper with GlobalData
On a positive note, Miltenyi Biomedicine completed a Phase II trial of its oncology candidate zamtocabtagene autoleucel.
Interested in more news in your inbox? Sign-up for our daily newsletter.Novartis Phase II ALS drug dropped after benefit-risk concerns
Novartis’s sotuletinib saw its Phase Transition Success Rate (PTSR) decrease in amyotrophic lateral sclerosis (ALS) after a Phase II trial was terminated. The PTSR dropped by 23 points to 29%.
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 (NCT04066244) status was updated from completed to terminated on ClinicalTrials.gov on 26 July, and GlobalData evaluated the asset on 29 July.
How well do you really know your competitors?
Access the most comprehensive Company Profiles on the market, powered by GlobalData. Save hours of research. Gain competitive edge.
Thank you!
Your download email will arrive shortly
Not ready to buy yet? Download a free sample
We are confident about the unique quality of our Company Profiles. However, we want you to make the most beneficial decision for your business, so we offer a free sample that you can download by submitting the below form
By GlobalDataAccording to the study’s ClinicalTrials.gov listing, the sponsor terminated the study after assessment of potential benefit-risk from available data.
The purpose of the open-label study was to characterize the safety, tolerability, and brain microglia response to sotuletinib. The study enrolled 28 patients before being terminated.
Sotuletinib acts as colony stimulating factor-1 receptor (CSF-1R) antagonist.
Phase I/II GBM termination
SonALASense’s aminolevulinic acid hydrochloride saw its PTSR decrease in recurrent glioblastoma multiforme (GBM) after a Phase I/II trial was terminated. The PTSR dropped by 12 points to 5%.
The Phase I/II trial’s (NCT05370508) status was updated from completed” to terminated on ClinicalTrials.gov on 26 July, and GlobalData evaluated the asset on 29 July.
According to the study’s ClinicalTrials.gov listing, the study was terminated due to funding challenges and not due to safety concerns.
The primary objective of the study was to evaluate dose-limiting toxicities, maximum tolerated dose, the maximum administered dose, and the recommended Phase II dose for a future study. The study enrolled 8 patients.
Aminolevulinic acid hydrochloride elicits therapeutic intervention by converting to protoporphyrin IX (PpIX), which upon activation by high-energy blue light, create reactive oxygen species and ultimately kills cancer cells. The Berkeley, California-based company is developing the drug candidate for the treatment of various cancers.
Phase II oncology trial completion
Miltenyi Biomedicine’s zamtocabtagene autoleucel saw its PTSR increase after a Phase II trial was completed. The drug candidate’s PTSR increased by six points in diffuse large B cell lymphoma to 38%, seven points in follicular lymphoma to 38%, and eight points to 39% in B cell non-Hodgkin lymphoma.
The Phase II trial’s (NCT03870945) status was updated from active, not recruiting to completed on ClinicalTrials.gov on 19 July, and GlobalData evaluated the asset on 22 July.
The trial investigated the safety, dose-finding and feasibility of zamtocabtagene autoleucel in patients with relapsed or resistant CD20 and CD19 positive B cell non-Hodgkin lymphoma. The study enrolled 12 patients.
Zamtocabtagene autoleucel elicits cytotoxic activity by acting on CD20- and CD19-expressing cancer cells and is under development for the treatment of B cell non-Hodgkin lymphoma including diffuse large B cell lymphoma, primary (thymic) large mediastinal B cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia, and small lymphocytic lymphoma.
Phase I GvHD trial terminated
Orca Biosystem’s TRGFT-201 has seen its PTSR drop after an investigator-led Phase I trial of the candidate in graft versus host disease (GvHD) was terminated. The PTSR for TRGFT-201 dropped in GvHD by nine points to 62%.
The status of the trial, which was being run by Stanford Cancer Institute, was changed from “Active, not recruiting” to terminated on ClinicalTrials.gov on 18 July. GlobalData evaluated the asset on the following day. The ClinicalTrials.gov listing did not disclose the reason for terminating the trial.
The Phase I trial (NCT03198234) investigated the use of TRGFT-201 for blood disorders. The study accrued only five patients out of the 30 originally anticipated to enrol.
TRGFT-201 exhibits therapeutic intervention by an undisclosed mechanism of action and is under development for the treatment of myelodysplastic syndrome, B cell acute lymphoblastic leukaemia, acute myeloid leukaemia, acute lymphoid leukaemia, hematopoietic stem cell transplant, myelofibrosis, blastic plasmacytoid dendritic cell neoplasm, chronic myelocytic leukaemia.
Phase I/IIa trial of gene therapy completes
Kolon Life Science Inc’s KLS-2031 saw its PTSR in radiculopathy increase by nine points to 41% after a Phase I/IIa study was completed.
The Phase I/IIa trial’s (NCT04238793) status was updated from active, not recruiting to completed on ClinicalTrials.gov on 25 July, with GlobalData evaluating the product on 30 July.
The double-blind, randomised, first-in-human study evaluated the effects of single ascending doses KLS-2031 in 18 participants, aged 18 to 75 years old. The purpose of the study was to determine the safety, tolerability, and analgesic effects of the epidurally injected therapy in patients with neuropathic pain from lumbosacral radiculopathy. The drug is being developed by Seoul, South Korea-based Kolon.
KLS-2031 is a gene therapy designed to employ an adeno associated virus (AAV) to deliver genes encoding and activating the glial cell line-derived neurotropic factor (GDNF), interleukin-10 (IL-10), and glutamate decarboxylase (GAD) 65. In doing so, the therapy suppresses the pain signal delivered to the brain and alleviates the pain area by mitigating neuroinflammation and neurotropic effects in the spinal cord. Radiculopathy refers to a condition wherein nerve roots are injured or damaged, which leads to pain.
Phase I monoclonal antibody trial suspended
Sanofi’s SAR-446422 saw its PTSR in autoimmune disorders decrease by 24 points to 32% after a Phase I healthy subject study was suspended. The trial’s suspension also resulted in the drug’s PTSR in inflammation decrease by 17 points to 22%.
The Phase I trial’s (ACTRN12623001176651) status was updated from recruiting to suspended on the Australian New Zealand Clinical Trials Registry (ANZCTR) on 28 July, with GlobalData evaluating the product on 30 July.
The randomised, placebo-controlled study was a two-part study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of ascending single and multiple doses of SAR-446422 in healthy adult participants aged 18 to 55 years old.
Part one was comprised of the single ascending dose study which included up to nine cohorts, with five cohorts being administered intravenous (IV) infusions and four cohorts receiving subcutaneous injections. The second multiple ascending dose portion of the study enrolled up to four cohorts that were treated with 30, 60, and 120 mg subcutaneous doses of treatment.
SAR-446422, a bispecific monoclonal antibody in development for autoimmune disorders and inflammatory diseases, is designed to target CD28 and the OX40 receptor. OX40 is a member of the tumour necrosis factor (TNF) receptor family, and its expression on T cells in a tumour environment is a marker of inflammation.
Read the last edition:
Read OnNeed 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.
