This week in clinical trials – 27th to 31st May

In this week’s clinical trials round-ups, we look at life sciences research and development announced during the week of 27th to 31st May, from early-stage onwards. During this week, pharmaphorum covered a breadth of news that veered both towards the negative - the overall survival data from AstraZeneca and Daiichi Sankyo’s TROPION-Lung01 study of datopotamab deruxtecan (Dato-DXd) in lung cancer, a TROP2-directed antibody-drug conjugate (ADC), not reaching statistical significance in the final analysis – and towards the positive, such as topline results from Johnson & Johnson’s MDD3001 study of seltorexant, an orexin-2 receptor antagonist, showing that the drug met all primary and secondary endpoints as a treatment for people with major depressive disorder (MDD) and symptoms of insomnia.

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

During the week of 27th to 31st May:

Arcturus Therapeutics, a San Diego, California-based late-stage clinical messenger RNA medicines company, announced it will be presenting new Phase 1b interim data for ARCT-032 – an inhaled investigation mRNA therapeutic to treat CF – at the European Cystic Fibrosis Conference in Scotland on 7th June. 

Cystic fibrosis is a life-shortening disease with a worldwide distribution. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in a reduction or absence of CFTR protein and/or function in the airways, causing insufficient chloride transport to maintain airway surface homeostasis. CF mucus is more difficult to clear, clogging the airways and leading to infection, inflammation, respiratory failure, or other life-threatening complications.

In the first four patients treated with ARCT-032, safety and toleration were good, with no serious adverse events. There was also observed “an encouraging trend towards lung function improvements […] after only two inhaled administrations”, according to Joseph Payne, president and CEO of the company. 

ARCT-032 has already received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) and Orphan Drug Designation from the US Food and Drug Administration (FDA) to treat CF. The ARCT-032 programme is supported by pre-clinical data in rodents, ferrets, and primates, as well as demonstrating restoration of CFTR expression and function in human bronchial epithelial cells. 

Positive results from a Phase 1 trial of AstraZeneca’s AZD0780, an oral small molecule PCSK9 inhibitor administered on top of statin treatment, were presented at the European Atherosclerosis Society in Lyon, France.

AZD0780 demonstrated a statistically significant reduction of 52% in low-density lipoprotein cholesterol (LDL-C) levels on top of rosuvastatin treatment, with 78% total reduction from baseline, in treatment-naive participants with hypercholesterolaemia. Elevated LDL-C levels in plasma is a key risk factor for cardiovascular disease and is estimated to cause 2.6 million deaths worldwide annually.

The Phase 1 trial included participants receiving AZD0780 30 mg or 60 mg daily versus placebo for four weeks. An additional arm including 35 participants with hypercholesterolaemia received rosuvastatin 20 mg for three weeks followed by AZD0780 30 mg or placebo for four weeks.

The trial assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD0780 in lowering LDL-C in plasma when administered as monotherapy and in combination with rosuvastatin. Preliminary data comparing dosing with food versus fasting indicates dosing flexibility with regard to food and no serious adverse events were reported.

Earlier this year, AZD0780 progressed into Phase 2 trials in patients with dyslipidaemia.

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the company. 

Vesper Bio, a clinical stage biotech specialising in sortilin receptor biology, announced completion of the single ascending dose stage of its first-in-human trial of VES001 – an oral, brain penetrant, small molecule sortilin inhibitor designed as a potentially disease-modifying treatment for the neuro-cognitive disorder fronto-temporal dementia (FTD) – in healthy volunteers. 

FTD, also known as fronto-temporal lobar degeneration (FTLD), is a group of brain disorders that cause degeneration in the frontal and temporal lobes of the brain. FTD impacts a person’s behaviour, judgement, communication, and ability to participate in all activities of daily living. It is the most common cause of dementia in people under the age of 60, and is often misdiagnosed as Alzheimer’s. 

Data returned from the study demonstrated the safety and tolerability of VES001 across the full range of doses tested and showed “excellent” pharmacokinetics and distribution to relevant parts of the brain. The data predicts a once or twice daily efficacious dose. 

Importantly, volunteers who received VES001 experienced “significant and robust” increases in levels of progranulin, demonstrating target engagement. Progranulin is a protein known to play a key role in promoting neuron survival, growth, and function. People with FTD(GRN) have inherited gene mutations associated with low progranulin levels, thought to account for a quarter of FTD cases.

Ultragenyx announced positive topline results from its Phase 3 GlucoGene study evaluating DTX401, an investigational gene therapy for the treatment of patients aged eight years and older with glycogen storage disease type Ia (GSDIa).

GSDIa is a serious inherited glycogen storage disease. It is caused by a defective gene coding for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar (glucose). GSDIa can be a devastating disease for patients and families, impacting how patients eat and sleep, as well as their physical activity.

Hypoglycemia in patients with GSDIa can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. 

Ultragenyx’ study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. 

Incannex Healthcare announced that patient dosing commenced in its Phase 2/3 RePOSA clinical trial to assess the safety and efficacy of IHL-42X in patients with obstructive sleep apnoea (OSA).

OSA is significantly undertreated, with no FDA approved prescribed medications. Patient compliance to positive air way pressure (PAP) devices is also low.

The RePOSA study is a Phase 2/3, randomised, double-blind clinical trial to determine the safety and efficacy of IHL-42X – a proprietary synergistic composition drug comprising low-dose dronabinol (2.5 mg), a synthetic form of tetrahydrocannabinol (THC), and acetazolamide ( 125 mg), a carbonic anhydrase inhibitor – in patients with OSA who are intolerant, non-compliant, or naïve to PAP.

The study includes a four-week Phase 2 dose ranging trial, followed by a 52-week Phase 3 factorial trial that will compare the optimal dose of IHL-42X to the component active ingredients at equivalent doses, as well as placebo.

There are 25 clinical trial sites recruiting patients in the United States.

Earlier studies demonstrated that IHL-42X reduced the apnoea hypopnoea index (AHI), the standard measure of OSA, by an average of greater than 50% at the low dose and 25% of those patients had an 80% reduction.