This week on Pipeline Moves we look into the termination of Novartis’s Phase I/Ib oncology trial. We also feature a Phase Ib/II solid tumour termination and missed primary endpoint in radiculopathy Phase IIa trial. On a good note, we review completions of Phase I/II in radicular pain and Phase I in autoimmune disorders and inflammation.
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Novartis terminates Phase I/Ib cancer trial
Novartis’s LHC-165 saw its Phase Transition Success Rate (PTSR) slump in three cancer indications after a Phase I/Ib trial was terminated. The PTSR dropped by 35 points to 25% in metastatic melanoma and head and neck cancer squamous cell carcinoma, and 21 points to 15% in solid tumours.
The Phase I/Ib trial (NCT03301896) was terminated owing to business reasons, according to its ClinicalTrials.gov listing. GlobalData evaluated the asset on 2 August after the update the day before. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The study anticipated to enrol 206 patients with advanced solid tumours to investigate LHC-165 as a single agent or in combination with PDR001 (spartalizumab). Some 45 patients were enrolled before termination. The primary endpoints investigated safety and ideal dosing. LHC-165 is a toll-like receptor 7 (TLR7) agonist activating immune cell responses; spartalizumab is a PD1-inhibitor.
Eliem’s radiculopathy asset misses primary endpoint
Eliem Therapeutics’s ETX-810 saw its PTSR drop in radiculopathy after a Phase IIa trial didn’t meet its primary endpoint. The PTSR decreased by 28 points to 14%.
Eliem issued a press release on 2 August indicating that the Phase IIa trial (NCT04778592) did not achieve its primary efficacy endpoint of statistical significant difference in the daily pain score against placebo. The trial enrolled 148 patients with lumbosacral radicular pain.
Eliem will discontinue further development of ETX-810, as per company’s press release. The candidate also failed in a Phase IIa trial (NCT04688671) recruiting subjects with diabetic peripheral neuropathic pain, reported in a 25 April press release. ETX-810 is a non-opioid pain killer targeting the palmitoylethanolamide (PEA) pathway, which modulates neuroinflammation and pain signalling.
Phase Ib/II solid tumour trial terminated
Clovis Oncology’s lucitanib saw its PTSR tumble 16 points to 19% in metastatic transitional tract cancer following the termination of a Phase Ib/II solid tumour trial. ClinicalTrials.gov updated the study’s listing from active, not recruiting to terminated on 28 July, and the PTSR change took effect the next day.
The Phase Ib/II SEASTAR trial (NCT03992131) was designed to evaluate lucitanib in combination with Clovis’s Rubraca (rucaparib) or Gilead Sciences’s Trodelvy (sacituzumab govitecan). The study had a recruitment target of 329 patients with an advanced/metastatic solid malignancy, but only enrolled 25 patients prior to the termination. There are no further plans of studying lucitanib in combination with either drug due to a change in development priorities, as per the trial listing. Gilead is a listed collaborator for the study.
Primary endpoints for the Phase Ib portion were adverse events and dose-limiting toxicities, and the Phase II primary outcome was overall response rate (ORR). Lucitanib is an angiogenesis inhibitor.
SpineThera completes Phase I/II radicular pain trial
SpineThera’s SX600 (dexamethasone acetate) saw its PTSR leap nine points to 32% in sciatica following the completion of a Phase I/II radicular pain trial. ClinicalTrials.gov updated the study’s listing from active, not recruiting to completed on 2 August, and the PTSR change took effect the next day.
The Phase II SALIENT trial (NCT03952377) enrolled 55 patients with radicular pain secondary to lumbar intervertebral disc herniation. Radicular pain describes symptoms stemming from a pinched nerve root in the spinal column, and sciatica is a common type of radicular pain that originates in the lower back. The primary endpoint was the proportion of subjects with at least a 50% improvement in the mean Worst Daily Leg Pain score after 60 days.
SX600 is a sustained-release version of dexamethasone, a glucocorticoid receptor agonist that can reduce pain by inhibiting prostaglandin synthesis. The drug, which is administered via a transforaminal epidural injection, is the lead candidate for Plymouth, Minnesota-based SpineThera.
Autoimmune disorders and inflammation Phase I completes
Q32 Bio’s ADX-914 saw its PTSR jump seven points in autoimmune disorders and inflammation following a Phase I trial completion. The PTSR now sits at 58% in autoimmune disorders and 42% in inflammation. ClinicalTrials.gov updated the study from recruiting to completed on 28 July, and the PTSR change took effect the next day.
The 42-subject Phase I study (NCT04485481) assessed the safety, pharmacokinetics, and pharmacodynamics of ADX-914 in healthy volunteers. The trial was placebo controlled and comprised of a single ascending dose and a multiple ascending dose component. Q32 Bio is based in Cambridge, Massachusetts, and the Phase I trial took place in Melbourne, Australia, as per ClinicalTrials.gov.
ADX-914 is an interleukin-7 receptor (IL-7R) alpha antagonist, which can restore immune regulation by inhibiting IL-7R signalling.
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 data points from the individual drugs, clinical trials, regulatory milestones, company, and financial databases.