This week on Pipeline Moves, we start by looking at the negative topline results from a Phase II systemic lupus trial. We continue by reviewing a Phase III trial in keratitis that started recruitment, and completions of two Phase II trials in dermatitis and obesity. We finish off the round-up with trial terminations in several oncology indications.

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Negative topline data from Phase II lupus trial

Nektar Therapeutics’s rezpegaldesleukin saw its Phase Transition Success Rate (PTSR) plunge in systemic lupus erythematosus (SLE) by 18 points to 13% after the announcement of negative topline data from a partner-sponsored Phase II trial.

On 23 February, Nektar issued a press release sharing negative topline data from the Phase II study (NCT04433585). GlobalData appraised the asset on 27 February. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The ISLAND trial studied the use of rezpegaldesleukin in 291 subjects with moderate to severe SLE. The trial was sponsored by Eli Lilly. In July 2017, the two companies announced their strategic collaboration to develop rezpegaldesleukin.

The study did not meet its primary endpoint of a four-point reduction in the SLEDAI-2K score in pre-defined study populations, based on the press release. However, clinically meaningful improvements were reported in the majority of the trial’s secondary endpoints at the drug’s 900mcg mid-dose level. This includes the response measured by the British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) assessment.

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By GlobalData

Lilly will not move rezpegaldesleukin to a Phase III trial in SLE, but the two companies aim to discuss the next steps for a planned Phase IIb trial in atopic dermatitis, as per the press release.

Rezpegaldesleukin, also known as LY3471851 and NKTR-358, acts as a selective regulatory T-cell inducing interleukin-2 (IL-2) conjugate. It targets the IL-2 receptor complex to stimulate regulatory T cells, which could address immune system imbalance in autoimmune and inflammatory conditions. SLE is the most common form of lupus, an autoimmune condition which leads to inflammation and tissue damage.

Phase III keratitis trial starts recruitment

ReGenTree’s timbetasin acetate saw its Likelihood of Approval (LoA) in keratitis jump 20 points to 44% after a Phase III trial began recruiting. ClinicalTrials.gov updated the trial listing from not yet recruiting to recruiting on 23 February, and the LoA change took effect the following day.

LoA is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm. LoA can be calculated for a drug by considering characteristics like therapy area, indication and molecule type.

The Phase III SEER-2 trial (NCT05555589) has a recruitment goal of 70 patients with neurotrophic keratopathy, also known as keratitis. As a primary endpoint, the study assesses the percentage of patients with complete healing of the Persistent Epithelial Defect (PED) at day 29. PED describes damage to the outer corneal layer, which is assessed using corneal fluorescein staining.

Previously, the Phase III SEER-1 trial of timbetasin acetate in neurotrophic keratopathy (NCT02600429) was terminated due to an unspecified business decision, as per the trial listing.

Timbetasin acetate, also known as RGN-259, is a synthetic protein containing thymosin b4 (Tβ4), which can regulate inflammation, wound healing, and cell protection in ophthalmic indications. Neurotrophic keratopathy is a degenerative corneal disease characterized by impairment of trigeminal innervation.

BMS completes Phase II dermatitis study

Bristol Myers Squibb’s branebrutinib saw its PTSR rise after a Phase II trial was completed. The PTSR increased by 30 points to 35% in atopic dermatitis.

The trial’s status was updated to completed on ClinicalTrials.gov on 24 February, and GlobalData evaluated the asset on 27 February.

The purpose of the Phase II trial (NCT05014438) was to evaluate the safety, efficacy, and tolerability of branebrutinib and BMS-986166, each, versus placebo for the treatment of atopic dermatitis. The trial enrolled only 17 patients out of the 150 originally anticipated to participate.

Branebrutinib acts as Burton’s tyrosine kinase (BTK) inhibitor. The drug candidate is under development for the treatment of moderate to severe atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, and primary Sjogren’s syndrome.

Lilly’s Phase II obesity trial completed

Eli Lilly’s retatrutide saw its PTSR rise after a Phase II trial was completed. The PTSR increased by eight points to 35% in obesity following the completion. The trial’s status was updated to completed on ClinicalTrials.gov on 21 February, and GlobalData evaluated the asset the following day.

The purpose of the Phase II trial (NCT04881760) was to learn more about how retatrutide affects body weight loss. The trial enrolled 338 patients who have obesity or are overweight.

Retatrutide acts by agonizing the GLP-1/GIP/glucagon receptors. The biologic candidate is under development for the treatment of type 2 diabetes and obesity.

Investigator-led Phase II tumour trial terminated

TerSera Therapeutics’s LX-1032 (telotristat ethyl) saw its PTSR drop after a Phase II trial in neuroendocrine tumours (NET) was terminated. The PTSR decreased by 10 points to 38% in NET. The trial was sponsored by Dr Lowell Anthony, a NET treatment specialist at the University of Kentucky Markey Cancer Center.

The investigator-led trial’s status was updated on ClinicalTrials.gov from recruiting to terminated on 20 February, and GlobalData evaluated the asset on 22 February. As per ClinicalTrials.gov, the study was terminated because the sponsor cancelled the research.

The open-label Phase II trial (NCT04543955) evaluated the effect of LX-1032 on the antitumor efficacy of Novartis’s Lutathera (lutetium Lu 177 dotatate) therapy in NETs. The study aimed to recruit 70 adult participants with metastatic or unresectable, histologically confirmed well-differentiated grade 1 and 2 NETs, but ended up recruiting only one patient.

The trial tested the hypothesis that inhibition of serotonin production with LX-1032 will complement the anti-tumour activity of Lutathera. LX-1032 is a tryptophan 5-monooxygenase inhibitor that acts by regulating serotonin synthesis. LX-1032 is marketed for carcinoid syndrome under the brand name Xermelo.

Termination of Phase I/II oncology trial

Basilea Pharmaceutica’s derazantinib saw its PTSR fall after a Phase I/II trial was terminated. The PTSR dropped by 26 points to 19% in adenocarcinoma of the gastroesophageal junction and by 23 points to 12% in gastric cancer.

The trial’s status was updated from ongoing, recruiting to terminated on ClinicalTrials.gov on 16 February, and GlobalData evaluated the asset the following day. The trial was terminated prematurely for administrative reasons not related to patient safety.

The purpose of Phase I/II trial (NCT04604132) was to evaluate the efficacy of derazantinib alone or in combination with paclitaxel, ramucirumab, or atezolizumab in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 genetic aberrations. The trial enrolled 47 patients.  

Derazantinib is a pan-FGFR and CSF1R inhibitor. The drug candidate is under development for the treatment of intrahepatic cholangiocarcinoma (iCCA), adrenocortical tumours, advanced solid tumours, and urothelial cell carcinoma.

Phase I urothelial cancer trial terminated

Bristol Myers Squibb’s Yervoy (ipilimumab) saw its PTSR decline after a Phase I oncology trial was terminated because the business objectives have changed. The PTSR decreased by 35 points to 44% in metastatic transitional (urothelial) tract cancer. GlobalData evaluated the asset on 27 February, after a ClinicalTrials.gov update on 24 February.

The open-label trial (NCT04311710) evaluated the drug levels of Yervoy as a monotherapy or in combination with Opdivo (nivolumab). The trial enrolled 21 patients with various tumour types.

Yervoy is a monoclonal antibody that targets cytotoxic T lymphocyte associated antigen 4 (CTLA-4). It was approved in various oncology indications in 2011.

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.