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September 6, 2022

Pipeline Moves: Novartis completes Phase II Sjögren’s syndrome trial, advancement prospects jump

The Clinical Trials Arena team also reviews a trial suspension in leishmaniasis, a termination in lymphoma and trial completions in endometriosis and dry eye disease.

By Clinical Trials Arena Team

This week on Pipeline Moves, we look into the Novartis completion of a Phase II trial in Sjögren’s syndrome. We follow it up by a Phase I suspension in visceral leishmaniasis, a Phase I termination in B-cell lymphoma, and two trial completions in endometriosis and dry eye disease.

Interested in seeing these updates in your inbox? Sign-up for our weekly Pipeline Moves newsletter. You can read last Tuesday’s edition here.

Novartis completes Phase II immune disorder trial

Novartis’s remibrutinib (LOU-064) saw its Phase Transition Success Rate (PTSR) in Sjögren’s syndrome grow by eight points to 34% after the completion of a Phase II study. The study’s status on its ClinicalTrials.gov listing changed from recruiting to completed on 26 August. GlobalData appraised the asset on 29 August.

The adaptive design Phase II study (NCT04035668) investigated the efficacy and safety of remibrutinib in patients with moderate to severe Sjögren’s syndrome. The trial measured the change in the EULAR Sjögren’s syndrome disease activity index (ESSDAI) at week 24 as the primary outcome. It tracked the occurrence of treatment-emergent adverse events (TEAEs) over 34 weeks as one of its 10 secondary endpoints. The study was initially anticipated to recruit 252 patients but enrolled 73.

Sometimes referred to as sicca syndrome, this immune system disorder is experienced through a constant dryness of the eyes and the mouth. Remibrutinib acts as a Bruton’s tyrosine kinase (BTK) inhibitor. Blocking BTK signalling inhibits the signalling of B cell receptors. Remibrutinib is also being studied in chronic spontaneous urticaria and other indications.

GSK suspends parasitic disease Phase I trial

GSK’s GSK3494245 saw its PTSR drop in visceral leishmaniasis, also known as Kala-Azar, after a Phase I trial was suspended due to an adverse event (AE) observed in one participant. The AE met the protocol-defined stopping criteria, according to the ClinicalTrials.gov entry. The PTSR declined by 28 points to 32%.

GlobalData evaluated the asset on 29 August after a ClinicalTrials.gov update on 26 August. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.

The double-blind, four-arm trial (NCT04504435) anticipated enrolling 54 healthy volunteers. The study was intended to investigate the safety, tolerability, and pharmacokinetic profile of GSK3494245 as a single dose in fed and fasted states. The trial was already once suspended due to an AE, GlobalData reported on 22 October 2021. 

Leishmaniasis is a parasitic disease spread by the bite of phlebotomine sand flies. GSK3494245 acts as a selective inhibitor of the chymotrypsin-like activity of the parasite’s proteasome.

Phase I lymphoma trial terminates

Humanigen’s lenzilumab saw its PTSR drop in four oncology indications after a sponsor-led Phase I trial in relapsed/refractory large B-cell lymphoma was terminated.

The Phase I trial was sponsored by Kite Pharma, which is owned by Gilead Sciences, and was testing the combination of lenzilumab with the latter’s Yescarta (axicabtagene ciloleucel), and chemotherapy in participants with relapsed or refractory large B-cell lymphoma.

The study ended when the entire development programme was terminated, according to the study’s ClinicalTrials.gov listing. The trial’s status was updated on ClinicalTrials.gov on 30 August, with GlobalData evaluating the asset on 1 September.

Lenzilumab’s PTSR decreased by 24 points in non-Hodgkin lymphoma settling at 31%. The PTSR also declined by 26 points to 30% in primary mediastinal B-cell lymphoma and 27 points to 32% in diffuse large B-cell lymphoma. The largest PTSR decrease was a 28-point drop to 31% in follicular lymphoma.

The open-label ZUMA-19 study (NCT04314843) was initially intended to be a Phase I/II study but the planned Phase II part was subsequently cancelled. The study was anticipated to recruit 36 patients but ended up enrolling only six subjects.

The primary endpoint for the Phase I part of the trial measured the percentage of participants experiencing treatment-related adverse events in a time period of up to 28 days. All participants who received an infusion of lezilumab and Yescarta will have the chance to transition to a separate long-term follow-up study.

Lenzilumab is a monoclonal antibody that targets the soluble granulocyte-macrophage colony stimulating factor (GM-CSF) and in turn, reduces inflammation. The drug was also under development for severe asthma, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), multiple sclerosis and psoriasis among other indications.

Bayer completes Phase I endometriosis trial

Bayer’s BAY-2395840 saw its PTSR jump in endometriosis after a Phase I study was completed. The PTSR increased by 14 points to 58%. GlobalData evaluated the asset on 27 August after the study’s ClinicalTrials.gov entry was updated the previous day.

The double-blind, placebo-controlled Phase I trial (NCT05517746) enrolled 63 healthy white men with no previous COVID-19 history. The study investigated the safety, tolerability, and pharmacokinetic profile of increasing single and multiple oral doses of BAY-2395840.

BAY-2395840 is a bradykinin B1 receptor antagonist that reduces the initiation of pain and inflammation. The drug is being developed to treat pain in people with endometriosis, and is also being investigated in a Phase II diabetic neuropathic pain trial. Endometriosis is a condition where womb-like tissue grows outside uterus, affecting one in 10 women.

Bayer reported that BAY-2395840 was safe and well tolerated at single doses up to 1,600 mg and multiple doses of up to 600 mg over a period of seven days, according to a Clinical Trial Results Synopsis published on 18 February 2022.

Phase II dry eye disease study completes

Glaukos’s GLK-301 saw its PTSR in dry eye disease spring by nine points to 44% after the completion of a Phase II study.

The study’s ClinicalTrials.gov page was updated on 30 August, with the status changing from active, not recruiting to completed. GlobalData appraised the asset on 1 September. The study’s completion was expected in May 2023 but ended on 27 July 2022. 

The double-masked Phase II study (NCT05119920) investigated the safety and efficacy of three doses of pilocarpine topical eye cream for subjects with dry eye disease. Also known as keratoconjunctivitis sicca, dry eye disease is caused by a lack of tears needed for hydration.

The study measured the mean change from baseline and at day 28 using the Eye Dryness Symptom Score on the Visual Analogue Scale (VAS) as one of its two primary endpoints. It also tracked the mean change from baseline in fluorescein staining of the inferior cornea at day 28 as a coprimary endpoint.

On 11 January 2022, the company announced the recruitment of the first subject for the trial. The trial was expected to enrol 220 subjects but concluded with 226 participants.

GLK-301 is an ophthalmic topical cream. Its active ingredient is pilocarpine, which functions as a cholinergic muscarinic agonist and stimulates muscarinic receptors and smooth muscle such as the iris sphincter muscle.

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.

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