This week in clinical trials: 2nd-5th January 2024

Despite the multiple challenges that faced clinical trials in 2023, according to GlobalData’s Pharmaceutical Intelligence Centre, some 22,338 studies were initiated.

As we begin 2024, in the interests of bringing in new (or, pardon the wordplay, news) resolutions, pharmaphorum intends to provide rolling coverage of what’s what in the world of clinical trials on a weekly basis, from early-stage onwards.

This week:

Vicore Pharma Holding AB is working to unlock the potential of a new class of drug candidates, angiotensin II type 2 receptor agonists (ATRAGs), with a focus on idiopathic pulmonary fibrosis (IPF). The final Phase 2a AIR data on C21 in IPF is expected in the first half of this year, and the Phase 2b ASPIRE initiation will take place this first half, also.

The Almee (formerly VP04) pivotal study COMPANION completion is on track. The digital therapeutic (DTx) developed by Vicore and Alex Therapeutics has been shown to reduce the psychological burden of living with pulmonary fibrosis (PF) in the COMPANION study, while the pre-clinical IMiD programme, inhaled thalidomide for IPF cough, is to be discontinued.

“Activation of the angiotensin II type 2 receptor is a potent protective mechanism with strong potential beyond IPF,” said Johan Raud, MD, PhD, Chief Scientific Officer of Vicore, “we are reviewing a number of indications where we believe this pathway can have a disease-modifying effect and pair well with the specific properties of our ATRAG molecules.”

Meanwhile, the global healthcare company Mundipharma announced that it has received European Commission (EC) approval for REZZAYO (rezafungin) for treatment of invasive candidiasis in adults, a severe infection of the bloodstream that affects the seriously ill, especially those with a weakened immune system. The mortality rate can be over 40%.

Based on positive results from the pivotal ReSTORE Phase III clinical trial and supported by the STRIVE Phase II clinical trials, and – following a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) – rezafungin represents the first new treatment option in over 15 years for patients with invasive candidiasis.

Mundipharma’s ReSTORE Phase III clinical trial demonstrated statistical non-inferiority for rezafungin, dosed once weekly, when compared to the current standard of care, caspofungin, dosed once daily.

Rezafungin has been granted Orphan Drug Designation for its use in the treatment of invasive candidiasis in the EU.

The positivity continues with Agios Pharmaceuticals announcing that its Phase 3 ENERGIZE study of oral treatment PYRUKYND (mitapivat) has met the primary endpoint and both key secondary endpoints in adults with non-transfusion-dependent (NTD) alpha- or beta-thalassaemia.

A total of 194 patients were enrolled in the study, with 130 randomised to mitapivat 100 mg twice-daily (BID) and 64 randomised to matched placebo.

Mitapivat – a pyruvate kinase (PK) activator – demonstrated a statistically significant increase in haemoglobin response rate compared to placebo and there was also statistical significance in change from baseline in both FACIT-Fatigue Score and haemoglobin concentration. The results of the ENERGIZE study support the potential of mitapivat to be the first oral therapy for NTD thalassemia patients, including those with alpha- or beta-thalassemia.

Agios is also advancing the fully enrolled Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia and expects to announce topline data from that 48-week study in mid-2024.

Biopharma Ultragenyx has announced that it has completed patient enrolment for its Phase ½ clinical trial of GTX-102 for the treatment of paediatric patients with Angelman syndrome, a rare, spontaneously occurring neurogenetic disorder caused by loss of function of the maternally inherited allele of the UBE3A gene.

GTX-102 is an investigational antisense oligonucleotide delivered via intrathecal (IT) administration, designed to target and inhibit expression of UBE3A antisense transcript (UBE3A-AS).

Non-clinical studies have shown that GTX-102 reduces the levels of UBE3A-AS and reactivates expression of the paternal UBE3A allele in neurons of the CNS. 

Ultragenyx’s GTX-102 has been granted Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA.

French biotech EG 427, meanwhile, has announced new pre-clinical results from multiple studies of gene therapy product EG110A in neurogenic detrusor overactivity (NDO) and overactive bladder (OAB).

In a non-clinical pharmacology study in an OAB model, EG110A showed similar efficacy and a strong safety profile compared to botulinum toxin A, notably without the increase in post-void residual urine volume - a known adverse reaction.

In the second study, which evaluated EG110A transgene expression over time in the dorsal root ganglia of treated animals, EG110A demonstrated persistent gene expression out to the final six-month time point, strongly supporting the potential for EG110A to provide long-term relief for patients suffering from NDO and OAB.

EG 427 specialises in the development of pinpoint DNA medicines for neurology, based on its unique non-replicative HSV-1 vector platform. It will be filing an Investigational New Drug (IND) application for EG110A in the first quarter of this year.

Orion Corporation and MSD (known as Merck & Co in the US and Canada) have initiated two pivotal Phase 3 clinical trials evaluating ODM-208/MK5684, an investigational CYP11A1 inhibitor, in combination with hormone replacement therapy (HRT), for the treatment of certain patients with metastatic castration-resistant prostate cancer (mCRPC).

Patients are currently enrolling in the trials: OMAHA1 (NCT06136624) and OMAHA2a (NCT06136650).

OMAHA1 is a randomised, open-label Phase 3 trial evaluating ODM-208/MK5684 in combination with HRT for the treatment of patients with later-line mCRPC who have failed one prior new hormonal agent (NHA) and one or two prior taxane-based chemotherapies compared to an alternative NHA (abiraterone or enzalutamide).

OMAHA2a is a randomised, open-label Phase 3 trial evaluating ODM-208/MK5684 in combination with HRT for the treatment of patients with front-line mCRPC who have failed one prior NHA compared to physician’s choice of NHA (abiraterone or enzalutamide).