This week on Pipeline Moves, we look into the completion of a Phase III trial in open-angle glaucoma. For Phase II trials, we investigate the termination of a severe swelling study, positive topline results in cervical dystonia, and a trial completion in two lung indications. We finish with two Phase I oncology trial completions.
Phase III glaucoma trial completed
NicOx ’s NCX 470 saw a rise in its Likelihood of Approval (LoA) of four points, settling at 46% in open-angle glaucoma after a Phase III NCX 470 trial was completed, according to a press release issued on 19 September.
The LoA change took effect on 21 September. LoA is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm. NCX 470 is a nitric oxide-donating prostaglandin analog designed to reduce intraocular pressure (IOP).
The randomised, multi-regional, double-masked Phase III (NCT04445519) study investigated the safety and efficacy of NCX 470 against the IOP standard of care latanoprost in subjects with open-angle glaucoma or ocular hypertension. The study enrolled 691 participants. The primary endpoint of the study measures the reduction of IOP from baseline in the study eye after three months.
Valbonne, France-based NicOx, and its China-based partner Ocumension Therapeutics are investigating NCX 470 in another Phase III trial (NCT04630808) in the same patient group. They expect topline results to be released after 2024, according to the press release.
Phase II trial in severe swelling terminated
Kalvista Pharmaceuticals ’s KVD-824 saw its Phase Transition Success Rate (PTSR) drop by 41 points to 17% in in hereditary angioedema (HAE) after a Phase II trial was terminated. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next. The termination was announced on 4 October, with GlobalData evaluating the asset on 6 October.
The KOMPLETE trial (NCT05055258) was terminated due to safety signals, specifically the observation of “liver enzyme elevations in multiple patients in all treatment groups”, according to the company’s press release. The company said it does not expect the safety profile of KVD-824’s current formulation to meet the requirements for a best-in-class oral prophylactic therapy.
The Phase II study evaluated the safety and efficacy of three dose levels of KVD-824 in adults suffering from type 1 or type 2 HAE. The trial recruited 33 patients and seven patients experienced either Grade 3 or Grade 4 elevations of liver enzymes within a timeframe of two to 12 weeks.
KVD-824 is a plasma kallikrein inhibitor that acts by blocking the dilation of vessels as well as oedema and inflammation caused by the activation of plasma kallikrein. HAE is caused by C1 esterase inhibitor deficiency and is characterised by recurrent episodes of severe swelling. The oral prophylactic was also under development for diabetic macular oedema.
The company will continue to enrol participants in the Phase III KONFIDENT trial (NCT05259917) which investigates KVD-900 (sebetralstat) as a potential oral, on-demand therapy for HAE attacks. KVD-900 is a distinct compound from KVD-824 with no observed treatment-related liver enzyme elevations in participants in clinical studies.
Positive Phase II topline results in cervical dystonia
AEON Biopharma’s ABP-450 (prabotulinumtoxin A) saw its PTSR rise by 16 points to 62% in spasmodic torticollis (cervical dystonia) after announcing positive topline results from a Phase II trial. GlobalData evaluated the asset on 26 September after a press release was issued on 23 September.
The triple-blind trial (NCT04849988) recruited 57 patients to investigate the asset as a monotherapy treatment for cervical dystonia in adults. Subjects were randomised to low, medium, high doses and placebo arms and received intramuscular injection into affected neck muscles. Cervical dystonia is a condition in which neck muscles contract involuntarily, causing head to twist or turn to one side.
All three treatment doses appear to be generally safe and well tolerated, achieving the primary endpoint of treatment-related serious adverse events. The secondary endpoints measured change at week four from baseline in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score. Low and mid dose regimens showed statistically significant improvement, whereas the highest dose nearly missed statistical significance.
ABP-450 is a proprietary botulinum toxin complex and blocks neuromuscular transmission by binding to acceptor sites on motor and sympathetic nerve terminals.
Completion of Phase II lung indication trial
Lung Therapeutics ’s LTI-01 saw its PTSR in two lung indications spring after the completion of a Phase II trial. The PTSR grew by nine points in empyema and pleural effusion, rising to 58% and 40%, respectively.
The study’s status on the ClinicalTrials.gov listing changed from recruiting to completed on 29 September, with GlobalData appraising the treatment the next day. Pleural effusion refers to the build-up of fluid in lung lining. Empyema refers to the collection of pus in the cavity between the lung and the membrane.
The quadruple masked study (NCT04159831) investigated the drug’s effect in subjects with infected, non-draining pleural effusions. The trial measured the incidence of referral to surgery, which marks the treatment’s failure, as the primary endpoint.
The primary endpoint was measured at Day 4, at hospital discharge or at time of treatment failure. The study also tracked the relative change in pleural opacity as a secondary endpoint at Day 4 or at time of treatment failure. It was anticipated to enrol 160 patients but finished with 44.
LTI-01 is a single-chain urokinase plasminogen activator, which reduces fibrinous scars in the lung cavity. Lung Therapeutics is headquartered in Austin, United States.
Phase I oncology trial completed
Celldex Therapeutics’s CDX-1140 saw its PTSR rise after a Phase I oncology trial completed. The PTSR increased by six points to 61% in ovarian cancer and seven points to 47% in hepatic (liver) tumours. GlobalData evaluated the asset on 30 September, following a ClinicalTrials.gov update the day before.
The open-label, non-randomised Phase I trial (NCT03329950) enrolled 132 patients with advanced malignancies, either with one line of treatment or none. The study determined the maximum tolerated dose (MTD) of CDX-1140 as a monotherapy or in combination with CDX-301 (FLT3L), Merck’s Keytruda (pembrolizumab), or chemotherapy (gemcitabine/nab-paclitaxel). The trial also evaluated the safety, tolerability, and efficacy of the different regimens.
CDX-1140 is an anti-CD40 monoclonal antibody designed to balance good systemic exposure and safety with potent biological activity.
Completion of Phase I oncology study
Holy Stone Healthcare ’s CA-102N saw its PTSR rise after the Phase I oncology trial was completed. The PTSR increased by seven points to 36% in solid tumours and to 62% in metastatic colorectal cancer. GlobalData evaluated the asset on 22 September after a ClinicalTrials.gov update the day before.
The open-label, dose escalation and expansion study (NCT03616574) recruited 37 patients. The first part of the study evaluated CA-102N as a monotherapy in subjects with advanced solid tumours. The second part of the study investigated the safety and tolerability of the asset in combination with Tokyo, Japan-based Taiho Pharmaceuticals’ Lonsurf (trifluridine + tipiracil hydrochloride) in patients with relapsed or refractory locally advanced or metastatic colorectal cancer. CA-102N targets CD44 expressing cells that are observed in colorectal cancer.
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.