In this week’s Pipeline Moves, we look at six different assets in various stages of drug development. First, we investigate the likelihood of further study by Roche in untreated blood cancers and by Celularity in glioblastoma multiforme after their respective Phase I trial suspension and termination. We also review Sino Biopharmaceutical’s and AbbVie’s respective assets in gastric cancer and ulcerative colitis.
On the back of Phase III trial completions by Citius Pharmaceuticals in blood cancer and by Pfizer’s respiratory syncytial virus asset, we look into their respective likelihood of approvals in those indications.
Roche suspends trial in blood cancers
Roche’s Polivy (polatuzumab vedotin) saw its Phase Transition Success Rate (PTSR) flop 36 points to 34% in B-cell non-Hodgkin lymphoma and sink 31 points to 40% in thymic carcinoma. This was after a Phase I trial in untreated, aggressive large B-cell lymphoma was suspended.
ClinicalTrials.gov updated the trial to “suspended (enrollment on hold; likely opening to accrual again)” on 21 January. The PTSR change took effect 24 January. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The 18-patient Phase I trial (NCT04231877), which tested Polivy in combination with chemotherapy, had the incidence of adverse events as its primary endpoint. Polivy consists of polatuzumab and vedotin. Polatuzumab is a monoclonal antibody that attaches to CD79b-positive cancer cells; vedotin is a toxin that kills these cancerous cells.
Polivy gained accelerated approval from the FDA to treat previously treated diffuse large B-cell Lymphoma in 2019. Polivy is marketed by Genentech, a subsidiary of Roche.
Celularity slumps in GBM
Celularity’s CYNK-001 saw its PTSR in recurrent glioblastoma multiforme (GBM) dive after the termination of its Phase I study. The PTSR fell by 32 points to 31%.
The open-label study (NCT04489420) had its status changed to “terminated” in a ClinicalTrials.gov update on 27 January, and the PTSR change occurred the next day. According to the trial registry, the study was terminated based on a business decision.
The study originally sought to find the asset’s maximum safe dose (MSD) or the maximum tolerated dose (MTD) in 36 subjects with GBM but enrolled only 3 individuals. CYNK-001 is an intravenous allogeneic natural killer-cell therapy designed to target tumour cells.
Sino Biopharm sees progress in gastric cancer
Sino Biopharm’s TQB-3101 had its PTSR in gastric cancer bounce after the completion of a Phase I study. The PTSR grew by 11 points to 65%.
The Shanghai, China-based, 16-subject study (NCT04804904) had its status changed to “completed” in a ClinicalTrials.gov update on 21 January. GlobalData updated its system on 24 January. The open-label study has multiple primary endpoints evaluating the effect of food on the pharmacokinetics of TQB-3101 in healthy participants.
TQB-3101 is an oral ALK (anaplastic lymphoma kinase) inhibitor, designed to block the uncontrollable proliferation of cancer cells caused by ALK. The study was sponsored by the Chia Tai Tianqing Pharmaceutical Group, a subsidiary of Sino Biopharm.
AbbVie concludes ulcerative colitis Phase IIa study
AbbVie’s ravagalimab for ulcerative colitis saw its PTSR leap nine points to 44% after its Phase II trial was completed. ClinicalTrials.gov updated the trial’s status on 21 January. The PTSR change took effect 24 January. Ravagalimab is a monoclonal antibody targeting CD40.
The Phase IIa study (NCT03695185) enrolled 42 patients with moderate-to-severe ulcerative colitis who had failed prior therapy. As a primary endpoint, the trial measured the percentage of patients with endoscopic improvement after 18 weeks, using the endoscopic subscore of the Mayo Clinic Score, a validated measure of ulcerative colitis activity.
Citius makes strides in blood cancers
Citius Pharma’ oncological candidate Ontak (denileukin diftitox) saw its Likelihood of Approval (LoA) in Sezary syndrome and mycosis fungoides bump by five points to 35% and by six points to 47%, respectively, after the completion of a Phase III study.
The Phase III study (NCT01871727) had its status changed to “completed” in a ClinicalTrials.gov update on 18 January. GlobalData updated its system on 19 January. LoA is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm. Both LoA and PTSR can be calculated for a drug by considering characteristics like therapy area, indication and molecule type.
The open-label study sought to evaluate the asset’s efficacy in subjects with recurrent or persistent cutaneous T-cell lymphoma (CTCL). Both Sezary syndrome and mycosis fungoides are indications classified as forms of CTCL, which affect the skin.
In the lead-in part of the trial, dose-limiting toxicities and maximum tolerated dose were primary endpoints. In the main trial, the primary outcome was overall response rate until disease progression and/or recurrence, or up to 30 months. Ontak is a recombinant DNA-derived cytotoxic protein, which acts as a cytotoxin.
Pfizer completes Phase III RSV trial
Pfizer’sPF-06928316 for respiratory syncytial virus (RSV) infections saw its LoA rise six points to 35% after a Phase III trial was completed. ClinicalTrials.gov updated the trial to “completed” on 25 January. The LoA change occurred on 27 January.
The Phase III study (NCT05096208) tested the clinical lot consistency of PF-06928316, also called RSVpreF, in 625 healthy participants. Three different lots of RSVpreF were tested alongside one placebo group to confirm manufacturing standards. Primary endpoints included measures of neutralizing titers and incidence of adverse events and prespecified systemic events.