This week in clinical trials: 20th to 24th May

In this instalment of our renewed clinical trials round-ups, we look at life sciences research and development announced during the week of 20th to 24th May, from early-stage onwards. During this week, pharmaphorum covered positive news on Vicore’s buloxibutid, an angiotensin II type 2 receptor agonist (ATRAG), and Endeavor’s ENV-101, a Hedgehog (Hh) signalling pathway inhibitor – both in development to treat idiopathic pulmonary fibrosis (IPF) – as well as GSK’s follow-up to its severe asthma therapy Nucala showing value in a pair of phase 3 trials, reducing exacerbations compared to placebo with dosing once every six months.

In this week’s round-up, there’s positivity to be shared also in diabetes, COPD, influenza, advanced solid tumours, and more.

Read on further for ongoing weekly news from studies across the globe.

During the week of 20th to 24th May:

Arecor Therapeutics’ (PDF) ultra-concentrated, ultra-rapid acting insulin candidate AT278 has demonstrated superiority in a Phase 1 clinical trial in overweight and obese people with Type 2 diabetes. AT278 has shown a significantly accelerated PK/PD profile compared to NovoRapid and Humulin R U-500 in people with Type 2 diabetes and high BMI, confirming previous trial results in people with Type 1 diabetes.

AT278 met all primary and secondary endpoints and it enables potential delivery of a highly concentrated, low volume injection for more effective mealtime glucose control to meet a growing unmet need in patients requiring high daily doses of insulin.

Back in February, Arecor Therapeutics named Dr Helen Parris as SVP, commercial and general manager of the company’s specialty pharma subsidiary Tetris Pharma. Parris came from Ipsen (via its Albireo Pharma acquisition) and prior to that worked at Gilead in multiple leadership roles.

Faron Pharmaceuticals, a clinical-stage biopharmaceutical company pursuing a CLEVER-1 receptor targeting approach to reprogramming myeloid cells to activate anti-tumour immunity in haematological and solid tumour microenvironments, provided the first data from patients treated during the Phase 2 part of the ongoing BEXMAB trial in myelodysplastic syndrome (MDS) patients that have failed a hypomethylating agent (HMA), also known as relapsed/refractory MDS (r/r MDS).

There are limited viable treatment options for r/r MDS and the mOS for these patient is only 5.6 months historically. The BEXMAB study is an open-label Phase 1/2 clinical trial investigating bexmarilimab in combination with standard of care (SoC) in the aggressive haematological malignancies of acute myeloid leukemia (AML) and MDS. The primary objective is to determine the safety and tolerability of bexmarilimab in combination with SoC (azacitidine) treatment.

The initial preliminary Phase 2 read-out from the BEXMAB Trial confirms earlier positive Phase 1 findings in MDS patients with prior HMA failure. The BEXMAB Phase 1 results have already indicated a high overall response rate (ORR) of 87.5% (7/8) amongst HMA-failed MDS patients treated with a combination of bexmarilimab + azacitidine. There are now a total of 14 HMA-failed MDS patients treated in both Phases 1 and 2 with this novel combination.

At the American Thoracic Society (ATS) International Conference in San Diego, CA, AstraZeneca presented late-breaking results from its Phase 2a COURSE trial, providing insight into tezepelumab’s impact on COPD exacerbations in patients with a broad range of eosinophil levels.

The Phase 2a COURSE trial was a proof-of-concept study in people with moderate to very severe chronic obstructive pulmonary disease (COPD) with a broad range of blood eosinophil counts (BEC) and irrespective of emphysema, chronic bronchitis, or smoking status.

The primary results showed that treatment with AstraZeneca and Amgen’s Tezspire (tezepelumab) led to a 17% numerical reduction in the annual rate of moderate or severe COPD exacerbations compared to placebo at week 52, which was not statistically significant.

Volta Medical presented positive results from the first transatlantic, multi-centre, randomised, controlled superiority trial titled Tailored vs. Anatomical Ablation Strategy for Persistent Atrial Fibrillation (TAILORED-AF) comparing artificial intelligence (AI)-assisted ablation procedure with conventional treatment for persistent atrial fibrillation (AF) patients.

The TAILORED-AF trial results were presented by principal investigator Professor Isabel Deisenhofer, of the Munich Heart Center, at the Heart Rhythm 2024 Late Breaking Clinical Trials and Science programme, demonstrating superiority in freedom from AF with or without anti-arrhythmic drugs at 12 months from a tailored cardiac ablation guided by AI when compared to pulmonary vein isolation (PVI) alone.

The AI solution is designed to assist cardiologists with real-time identification of specific abnormal electrograms (EGMs), known as spatio-temporal dispersed EGMs. Previous landmark studies looking at ablation strategies for persistent AF patients demonstrated a lack of a consistent ablation strategy that is effective for patients, with a clinical success rate in past trials of 50%.

Patients were enrolled in Europe and the United States. A total of 187 patients underwent a tailored cardiac ablation guided by Volta’s AI technology in addition to PVI (Tailored cohort), and 183 patients received the conventional treatment of PVI-only (Anatomical cohort). All were followed up for 12 months and a total of 51 electrophysiologists at 26 centres in 5 countries participated.

Johnson & Johnson announced data from the Phase 3 QUASAR maintenance study through 44 weeks in adults with moderately to severely active ulcerative colitis (UC), showing a 73% clinical remission rate, meeting the primary endpoint in addition to all nine major secondary endpoints, including endoscopic normalisation, while data from two 48-week GALAXI studies (GALAXI 2 and 3) in treatment of patients with moderately to severely active Crohn’s Disease (CD) demonstrated a sustained efficacy through Week 48, and a superior efficacy versus Stelara (ustekinumab).

The Phase 3 QUASAR maintenance study was a randomised-withdrawl, double-blind, placebo (PBO)-controlled study and demonstrated the efficacy and safety profile of Tremfya (guselkumab) through 44 weeks in adult patients with moderately to severely active UC, while data from the GALAXI 2 and 3 studies showed that both dose regimens of guselkumab demonstrated superior and clinically meaningful differences of efficacy compared to ustekinumab on multiple endoscopic endpoints in pooled analyses.

UCB announced publication in The Lancet of Phase 3 bimekizumab trial results in moderate to severe hidradenitis suppurativa (HS). The BE HEARD I and BE HEARD II studies are the first Phase 3 trials to evaluate the efficacy and safety of an IL-17A and IL-17F inhibitor (bimekizumab) in the treatment of adults with moderate to severe HS.

HS is one of the most burdensome, chronic, systemic, inflammatory skin diseases that can have a profound impact on patients’ health-related quality of life. Lead investigator Alexa B Kimball of the Beth Israel Deaconess Medical Center and Professor of Dermatology at Harvard Medical School commented: ““The Phase 3 studies with bimekizumab represent a significant milestone for the hidradenitis suppurativa community, and they include HiSCR75, a high threshold endpoint, as a key ranked secondary outcome. In these studies, bimekizumab consistently demonstrated sustained improvements in clinical- as well as patient-reported outcomes for people with moderate to severe disease.”

In April 2024, UCB announced that the European Commission granted marketing authorization for bimekizumab for the treatment of active moderate to severe HS in adults with an inadequate response to conventional systemic HS therapy. In April 2024, UCB also announced that the US FDA had accepted for review the supplemental biologics license application for bimekizumab-bkzx for the treatment of adults with moderate to severe HS.

Pneumagen presented positive Phase 2 Influenza Human Challenge Study data on Neumifil, its broad-spectrum antiviral, intranasal drug for the prophylaxis and treatment of viral respiratory tract infections (RTIs), at the American Thoracic Society (ATS) 2024 conference, with Neumifil delivering statistically significant reductions in influenza symptomatic infection rate, symptom severity, and viral load.

The Controlled Human Infection Model (CHIM) study had healthy volunteers challenged with influenza virus following administration of Neumifil. Penumagen’s CEO, Douglas Thomson, commented: “Based on these promising proof-of-concept results […] that reinforce the clinically significant reduction in both the incidence and severity of symptomatic influenza infection, we now look forward to advancing Neumifil into further clinical studies where its broad spectrum of activity offers significant potential.”

Further trials are expected to include Neumifil’s application in Chronic Obstructive Pulmonary Disease (COPD). It is also thought to hold potential for preventing exacerbations in people with asthma.

Nimbus Therapeutics announced new Phase 1 and 2 data on its investigational therapy NDI-101150, a novel, small molecule haematopoietic progenitor kinase 1 (HPK1) inhibitor for the treatment of advanced solid tumours, to be presented in a poster at ASCO.

HPK1 is a MAP4K family kinase and plays a key role in regulating T-cells, B-cells, and dendritic cells, producing a robust anti-tumour response. In contrast, traditional checkpoint inhibitors only activate T-cells. Based on prior research, NDI-101150 was found to be more than 300x more selective for HPK1 than related proteins in the MAP4K family – potentially reducing off-target effects.

The new Phase 1/2 data showed a clinical benefit in 5 out of 30 (16.7%) response-evaluable patients, with one patient with renal cell carcinoma (RCC) exhibiting a complete response, one patient with RCC exhibiting a partial response, and three patients with RCC, pancreatic cancer, and endometrial cancer maintaining durable stable disease for more than 6 months.

The Phase 1/2 multi-centre, open-label trial has been designed to assess NDI-101150 as a monotherapy (50-200 mg dose) and in combination with 200 mg pembrolizumab in the treatment of adults with advanced solid tumours. The results being presented at the ASCO Annual Meeting include updated data from 44 patients in the dose escalation cohorts and additional data from 15 patients in the dose expansion cohorts.

Takeda acquired a promising immunotherapy candidate, TAK-279, from Boston-based Nimbus Therapeutics, and on the sidelines of JP Morgan back in January this year Takeda VP and TAK-279 franchise lead Graham Heap sat down with pharmaphorum editor-in-chief Jonah Comstock to discuss the highly selective allosteric TYK-2 inhibitor. You can watch the interview here.