This week on Pipeline Moves, we start by looking at completions of Phase II trials in Parkinson’s disease and asthma, and a Phase I/II trial in several oncology indications. We continue by investigating trial terminations in oncology indications and sickle cell disease.
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Completion of Phase II PD trial
Hope Biosciences’s stem cell therapy for Parkinson’s disease (PD) saw its Phase Transition Success Rate (PTSR) rise nine points to 33% following the completion of a Phase II trial.
ClinicalTrials.gov updated the trial listing from active, not recruiting to completed on 8 March, and the PTSR change took effect the next day. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The 24-patient Phase II study (NCT04928287) tested autologous adipose tissue-derived mesenchymal stem cells called HB-adMSCs, which are designed to restore cell function in neurodegenerative diseases.
The study had 17 primary endpoints, including change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MD-UPDRS) Part II, which assesses motor function in daily living. Additional primary endpoints included multiple measures of adverse events (AEs), laboratory values, vital signs, and physical examination results.
The Phase II study was sponsored by the non-profit Hope Biosciences Stem Cell Research Foundation, with the pharmaceutical company Hope Biosciences listed as a collaborator. Both Hope Biosciences and its associated non-profit are based in Sugar Land, Texas.
AstraZeneca completes Phase II asthma trial
AstraZeneca’s tozorakimab (MEDI3506) saw its PTSR rise in asthma by 10 points to 34% after the completion of a Phase II trial. The study’s status on ClinicalTrials.gov was changed from active, not recruiting to completed on 2 March, with the PTSR being updated the next day.
The purpose of the randomised, double-blind, placebo-controlled trial (NCT04570657) was to assess the efficacy and safety of tozorakimab in adult subjects with uncontrolled moderate-to-severe asthma. The primary outcome measure was assessing the effect of tozorakimab compared with placebo on lung function between baseline and week 16. A total of 250 subjects were enrolled in the study.
Tozorakimab is a monoclonal antibody (mAb) that acts by targeting interleukin-33 (IL-33). The mAb is under development for the treatment of diabetic kidney disease, Covid-19, chronic bronchitis, asthma, acute respiratory failure and chronic obstructive pulmonary disease (COPD).
Phase I/II oncology trial completed
Intensity Therapeutics’s INT-2306 saw its PTSR rise after a Phase I/II trial was completed. The drug’s PTSR increased by seven points to 29% in metastatic hepatocellular carcinoma (HCC), nine points to 33% in glioblastoma multiforme (GBM), and nine points to 44% in thyroid cancer following the completion.
The trial’s status was updated to completed on ClinicalTrials.gov on 2 March, and GlobalData evaluated the asset the following day.
The purpose of the Phase I/II trial (NCT03058289) was to evaluate the safety of intratumorally dosed INT-2306 in subjects with advanced refractory cancers. The trial enrolled 110 patients, an increase over the 60 originally anticipated to participate.
INT-2306 elicits a cytotoxic effect by interfering with mitosis to inhibit DNA synthesis. The drug candidate is under development for the treatment of solid tumours and various cancers.
Investigator-led Phase II oncology trial terminated
AstraZeneca’s Imfinzi (durvalumab) saw its PTSR fall after a Phase II trial was terminated. The drug’s PTSR dropped by 12 points to 42% in metastatic adenocarcinoma of the pancreas.
The trial’s status was updated to terminated on ClinicalTrials.gov on 8 March, and GlobalData evaluated the asset the following day. The trial was terminated prematurely due to slow enrolment.
The purpose of the single-institution, single-arm, investigator-led Phase II trial (NCT03490760) was to test Imfinzi in combination with radiation therapy in patients with metastatic pancreatic cancer who have progressed after first-line chemotherapy.
Imfinzi is an anti-PD-L1 monoclonal antibody (mAb) marketed and under development for the treatment of various cancers.
BMS terminates Phase I/II AML trial
Bristol Myers Squibb’s BMS-9001 saw its PTSR fall in acute myelocytic leukaemia (AML) after a Phase I/II trial was terminated. The drug’s PTSR dropped by 23 points to 16% in AML.
The Phase I/II trial’s (NCT04748848) status was updated to terminated on ClinicalTrials.gov on 2 March, and GlobalData evaluated the asset the following day. As per ClinicalTrials.gov, the trial was terminated prematurely because business objectives changed.
The purpose of the Phase I/II trial was to evaluate the preliminary efficacy, safety, and tolerability of BMS-9001 in combination with Venclexta (venetoclax), marketed by AbbVie and Genentech, a division of Roche, and azacitidine in relapsed and refractory AML. The trial only enrolled one patient, before being terminated.
BMS-9001 acts by inhibiting lysine-specific demethylase 1 (LSD-1). The drug candidate is under development for the treatment of relapsed and refractory non-Hodgkin’s lymphoma, metastatic castration-resistant prostate cancer (mCRPC), and various relapsed and refractory solid tumours.
Phase I blood disorder trial terminated
Mitobridge’s ASP-8731 saw a drop in its PTSR by 26 points, settling at 29% in sickle cell disease. The PTSR change took place on 6 March following a Phase I trial termination.
The trial’s Clinicaltrials.gov status changed from active, not recruiting to terminated on 1 March. It was terminated due to the protocol-defined stopping criteria being met. Mitobridge is a subsidiary of Astellas Pharma, which sponsored the trial.
The trial (NCT05167526) planned to find a suitable dose of ASP-8731 and check for medical problems at each dose in healthy adults. The trial investigated eight primary endpoints to do with different patient laboratory abnormalities and adverse events.
ASP-8731 is an oral drug that targets the transcription regulator protein BACH1 which regulates the oxidation of the heme protein. The drug acts by inhibiting BACH1, increasing the expression of antioxidant and HbF genes, preventing or reducing disease progression. Sickle cell disease is caused by a gene mutation that affects red blood cell development, preventing them from carrying oxygen in the heme proteins.
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.