This week on Pipeline Moves, we kick off by looking at Novo Nordisk’s completion of a Phase III trial of liraglutide in children aged under 12.
Meanwhile, Pfizer’s maplirpacept saw its transition prospects fall after a Phase I oncology termination and Les Laboratories saw its transition prospects fall after a Phase I oncology drug trial was terminated.
On a positive note, Vaxctye has reported positive topline data from its Phase I/II pneumonia vaccine trial, sending its phase transition prospects up while Atensa Therapeutics’s Phase I/II trial of its rare disease ophthalmology drug met all endpoints.
Novo Nordisk’s liraglutide Phase III win in paediatric patients
Novo Nordisk’s liraglutide saw an increase in its Likelihood of Approval (LoA) by 13 points to 50% in obesity following the completion of a Phase IIIa trial in paediatric patients under 12.
An article, published on 10 September in the New England Journal of Medicine, outlined that the trial (NCT04775082) achieved its primary endpoint of change in body mass index (BMI) between patients aged 6 to 11 years treated with liraglutide versus placebo. GlobalData assessed the asset on 12 September.
In the trial, 56 weeks after initial dosing, mean BMI change from baseline was -5.8% among liraglutide-treated participants and +1.6% for those given placebo — a -7.4% difference. BMI was reduced by at least 5% in 46% of treated patients and 9% in the placebo group. The rates of adverse events were similar between study arms.
Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue. The drug ensures insulin is released only in response to excessive glucose levels and inhibits appetite. It is marketed as Saxenda for obesity and Victoza as a treatment for type 2 diabetes. Novo Nordisk is also studying the drug in Alzheimer’s disease and Parkinson’s disease in Phase II trials.
The drug’s LoA is identified via GlobalData’s analysis using a combination of machine learning and a proprietary algorithm.
Pfizer reports Phase I termination
Pfizer’s maplirpacept saw its Phase Transition Success Rate (PTSR) drop by in two indications, following the termination of a Phase I trial. The drug’s PTSR was reduced by 32 points to reach 35% in peripheral T cell lymphoma (PTCL) and by 14 points to 54% and B cell Hodgkin lymphoma. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The Phase I trial’s (NCT03530683) status was updated from active, not recruiting to terminated on ClinicalTrials.gov on 29 August, and GlobalData evaluated the asset on 4 September.
The open-label, non-randomised trial evaluated maplirpacept safety and efficacy in a dose-escalation Phase Ia portion and by comparing monotherapy with a series of combined therapies in the Phase Ib part.
According to the study’s ClincalTrials.gov listing, the trial termination was a business decision by Pfizer that was not due to any safety concerns, requests from regulatory authorities, changes to the benefit/risk profile or any new concerns regarding the investigational product.
Maplirpacept is an immune checkpoint inhibitor which alleviates CD47-mediated immune suppression and promotes anti-tumour responses. It is being developed by Pfizer in numerous cancer settings.
Phase I/II trial of pneumonia vaccine completes
Vaxcyte’s VAX-31 saw its PTSR in streptococcal pneumonia increase by 16 points to 54% after a Phase I/II trial studying the vaccine reported positive topline data.
The clinical-stage vaccine company released topline data for the Phase I/II trial (NCT06151288) on 3 September, with GlobalData evaluating the product on 5 September.
The observer-blind, randomised, dose-finding study evaluated the safety, tolerability, and immunogenicity of a single injection of VAX-31 compared to Pfizer’s Prevnar 20 (PVC20). The Phase I portion of the study evaluated three dose levels of VAX-31 in 64 healthy adults aged 50–64 years old, while the Phase II part evaluated 951 healthy adults aged 50 years and older.
As per the press announcement, VAX-31 demonstrated robust opsonophagocytic activity (OPA) immune responses for all 31 serotypes at all the studied doses.
VAX-31 is a conjugate vaccine designed to prevent invasive pneumococcal disease (IPD) by stimulating a humoural and cellular immune response, which results in the production of B lymphocytes and T lymphocytes. IPD is defined as more severe and invasive pneumococcal infections caused by the bacterium Streptococcus pneumoniae. The disease is especially serious in infants, young children, older adults, and individuals who are immunocompromised or have certain chronic conditions.
Phase I/II rare disease trial meets endpoints
Atsena Therapeutics’s ATSN-101 has seen its PTSR rise in Leber Congenital Amaurosis (LCA) after a Phase I/II trial studying the same indication achieved its endpoints. The PTSR for ATSN-101 increased in LCA by 11 points to 58%.
An article published in The Lancet on 7 September stated that the trial recorded clinically significant improvements in retinal sensitivity that were sustained in patients receiving the high dose. The report also stated that ATSN-101 was well tolerated 12 months after treatment, with no drug-related serious adverse events. GlobalData evaluated the asset on 9 September.
In patients who received the high dose, the mean change in dark-adapted full-field stimulus test (FST) was 20.3 dB for treated eyes and 1.1 dB for untreated eyes after 12 months. Improvements were observed as early as day 28. Modest improvements in best-corrected visual acuity (BCVA) were also observed.
The Phase I/II trial (NCT03920007) was an open label dose escalation study of sub-retinally injected ATSN-101. The study was separated into two parts including a dose escalation phase (part A) and a dose expansion phase (part B). The trial enrolled 15 patients with LCA due to a mutation in the GUCY2D gene. The rare disease affects less than 100,000 people worldwide and causes a significant amount of vision loss as early as infancy.
Durham, North Carolina-based Atsena’s ATSN-101 is a gene therapy that uses an adeno-associated virus serotype 5 (AAV5) vector encoding the human retinal guanylate cyclase 1 gene.
Oncology Phase I trial of two drugs terminated
Les Laboratoires Servier’s S-64315 (MIK-665) and S-65487 (VOB-560) saw their PTSR decline in non-Hodgkin lymphoma (NHL), acute myeloid leukaemia (AML) and multiple myeloma (MM) after a Phase I trial was terminated.
S-64315’s PTSR decreased by 25 points to 31% in relapsed/refractory AML, and by 36 points to 32% in NHL. S-65487’s PTSR decreased by nine points in four indications to reach 56% in MM, 55% in NHL, 54% in relapsed AML, and 52% in refractory AML.
The Phase I trial’s status was updated on ClinicalTrials.gov from active, not recruiting to terminated on 4 September and GlobalData evaluated the asset on the next day. The study’s termination was due to business reasons according to the trial’s ClinicalTrials.gov listing. The trial was sponsored by Novartis.
Les Laboratoires Servier SAS (Servier) is a private parent company that develops, manufactures, and markets drugs for CNS disorders, cardiovascular diseases, oncology, respiratory diseases, haematological disorders and others, headquartered in Suresnes, Ile-de-France, France.
The first-in-human, open-label, non-randomised Phase I trial (NCT04702425) evaluated the safety of doses and schedules of the combination of S-64315 and S-65487 in 37 patients with NHL, MM or AML. The study’s co-primary endpoints assessed the incidence and severity of adverse events, serious adverse events, changes in laboratory values, vital signs and dose-limiting toxicities as well as other measures in a time frame of up to 18 months.
S-65487 and S-64315 are selective inhibitors of the B cell lymphoma 2 (BCL2) protein and of the myeloid cell leukaemia 1 (MCL1) protein, respectively. Both proteins are over-expressed and may protect tumour cells from cell death, thus both assets act by blocking these proteins and preventing tumour growth and survival.
Read the last edition:
[Link src="https://www.clinicaltrialsarena.com/features/oncology-cell-therapy-termination-investigator/" title="Pipeline Moves: Investigator-led oncology cell therapy trial terminated" font-size="20px"]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.
