In this week’s edition of Pipeline Moves, the Clinical Trials Arena team studies Nektar Therapeutics’s termination of a Phase I/II cancer trial. We also dive into the termination of a Phase II peanut allergy study and a Phase I traumatic brain injury trial.
Meanwhile, we review Cara Therapeutics’s positive update on a Phase II trial in notalgia paresthetica, as well as a Phase III study completion in Stargardt disease.
Nektar terminates Phase I/II cancer study
Nektar’s NKTR-262 saw its PTSR (Phase Transition Success Rate) plummet across seven cancer indications after the termination of the Phase I/II REVEAL trial. The termination was based on overall results from the Phase I portion, which led to the trial’s premature end, according to its ClinicalTrials.gov listing. The termination was not based on safety reasons, it notes.
The PTSR fell by 20 points to 12% in sarcomas, renal cell carcinoma, and Merkel cell carcinoma. It dropped by 18 points to 14% in metastatic melanoma and head and neck squamous cell carcinoma. The PTSR also dove by 16 points to 6% in solid tumours, while falling by 12 points to 11% in colorectal cancer. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
REVEAL’s (NCT03435640) status was updated on June 29, with the PTSR changing a day later. The study initially anticipated to enrol 393 patients, but eventually recruited 64 participants. The Phase I is the dose escalation portion of the study, while the Phase II is for dose expansion.
The trial was investigating the use of NKTR-262 in combination with bempegaldesleukin (NKTR-214), as well as a triple approach with Bristol-Myers Squibb’s Opdivo (nivolumab). Patients had either locally advanced or metastatic solid tumour malignancies. NKTR-262 is a toll-like receptor 7 and 8 agonist, while bempegaldesleukin targets the interleukin-2 receptor.
Peanut allergy study terminated
Cour Pharmaceuticals’s CNP-201 saw its PTSR decline in peanut allergy following a Phase Ib/IIa trial termination. The PTSR dropped by 11 points, settling at 39%. The termination update was made on June 29, with GlobalData evaluating the asset the next day.
The Phase Ib/IIa study (NCT04950504) was terminated due to lagging enrolment. Its ClinicalTrials.gov listing states that a separate Phase Ib/IIa study (NCT05250856) was opened, with the first patient recruited on March 14.
The terminated Phase Ib/IIa study aimed to evaluate CNP-201 in participants diagnosed with peanut allergy with a history of non-severe anaphylaxis. The trial was initially anticipated to recruit 48 participants but ended up only recruiting three subjects. The trial initially aimed to enrol participants between the ages of 16–55 but then was changed to 16–35 years old on March 11.
The new 58-subject Phase Ib/IIa study aims to recruit participants aged between of 16–55. As with the first trial, it is targeting patients with non-severe anaphylaxis. The study has coprimary endpoints looking into adverse events and serum cytokines. CNP-201 is comprised of purified peanut extract drug substance, dispersed within negatively charged poly(lactic-co-glycolic acid) particles to modify binding.
Pinteon terminates Phase I trial
Pinteon Therapeutics’s PNT-001 saw its PTSR in traumatic brain injury (TBI) drop nine points to 56% following a Phase I trial termination. ClinicalTrials.gov updated the trial listing from recruiting to terminated on June 29, and the PTSR change took effect the next day.
The Phase I study (NCT04677829) was terminated due to administrative reasons and not safety concerns, according to the trial listing. The study had an enrolment goal of 64 subjects but only recruited one. Primary endpoints for the placebo-controlled, ascending-dose trial included measures of adverse events, vital signs, and a neurological exam.
PNT-001 is an intravenously administered monoclonal antibody that inhibits the tau protein, designed to prevent the spread of misfolded tau in TBI. The Phase I trial recruited patients who were hospitalised due to documented evidence of TBI and could receive treatment within 24 hours of their brain trauma.
Positive notalgia paresthetica data announced
Cara’s oral difelikefalin saw its PTSR in notalgia paresthetica spring 15 points to 30% after the company announced positive topline Phase II results. The press release was revealed on June 30, with GlobalData appraising the asset on July 4.
The 120-participant Phase II KOMFORT study (NCT04706975) studied twice daily, oral difelikefalin for moderate-to-severe pruritus in notalgia paresthetica patients. KOMFORT met its primary endpoint of score change in the Worst Itch-Numeric Rating Scale (WI-NRS). While patients in the treatment arm had a 4-point decrease, those on placebo only had a 2.4-point drop (p=0.001). Improvements were seen as early as week one and sustained to week eight.
An intravenous bolus injection version of difelikefalin is marketed in the US by Vifor Pharma under the brand name Korsuva for pruritus linked to chronic kidney disease in adult patients on haemodialysis. Notalgia paresthetica is a chronic, sensory neuropathy in the upper back.
Phase III Stargardt disease study completed
Kubota Vision’s emixustat hydrochloride saw its Likelihood of Approval (LoA) in Stargardt disease increase by four points to 12% following the completion of a Phase III trial. A company press release announced the trial’s completion on June 24, and the LoA change took effect June 28. LoA is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm.
The Phase III SeaStar trial (NCT03772665) tested the mean rate of change in total area of macular atrophy as the primary endpoint. SeaSTAR had a target enrolment of 162 patients, but 194 were enroled due to high interest in the study, according to the press release. Patients were randomised 2:1 to receive 10mg of emixustat or placebo during the 24-month study. The trial database will be locked in the Q3 2022, as per the company.
Stargardt disease, also known as juvenile macular degeneration, is a rare genetic disease that affects the retina, leading to progressive vision loss in children. Emixustat inhibits the enzyme retinal pigment epithelium protein 65, thereby modulating the visual cycle. Both the FDA and the EMA have granted emixustat orphan drug status for the treatment of Stargardt disease. Kubota Vision is a wholly owned subsidiary ofKubota Pharmaceuticals.
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.