10th to 14th June – This week in clinical trials

In the latest instalment of our clinical trials round-ups, we look at life sciences research and development announced during the week of 10th to 14th June, from early-stage onwards.

During this week, pharmaphorum covered a broad range of news: from the last three slots of the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot scheme being filled by Moderna, Myrtelle, and Calico Life Sciences, to Moderna saying it has become the first company with phase 3 data on a combined vaccine for both COVID-19 and influenza, and from Pfizer’s $7 billion partnership with venture capital firm Flagship Pioneering announcing that it will work with biotech start-up ProFound Therapeutics to find first-in-class protein therapeutics with potential in obesity to the converse disappointing news for Pfizer’s Duchenne muscular dystrophy (DMD) gene therapy after it failed a phase 3 trial – this has been a week of highs and lows for the pharmaceutical industry.

And no less so for the companies and studies mentioned below.

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

During the week of 10th to 14th June:

Clinical-stage biotech NMD Pharma A/S announced that it had dosed the first generalised myasthenia gravis (gMG) patient in its Phase 2b clinical trial of NMD670, having received FDA IND clearance in March this year to conduct the study.

MG is a rare and chronic autoimmune disease where IgG antibodies disrupt communication between nerves and muscles causing debilitating and potentially life-threatening muscle weakness. It commonly affects the muscles that control the eyes and eyelids, facial expressions, chewing, swallowing, and speaking, but in most patients, it eventually impacts most skeletal muscles. More than 85% of people with MG progress to generalised MG within 18 months. There are approximately 100,000 people in the European Union, and more than 65,000 people in the United States and 20,000 people in Japan with living with gMG.

The Phase 2b trial is a dose range-finding, double-blinded, placebo-controlled study of NMD670 - a twice daily, small molecule oral inhibitor of the skeletal muscle specific CIC-1 chloride ion channel – over 21 days in patients with gMG who are anti-acetylcholine receptor (AChR), or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

The study will evaluate changes in the Quantitative Myasthenia Gravis Total Score and the Myasthenia Gravis Activities of Living, alongside other endpoints. It is being conducted at both US and European clinical sites.

NMD Pharma recently published positive Phase 1/2a data in the journal Science Translational Medicine, establishing the first clinical proof-of-mechanism of CIC-1 inhibitors in patients suffering from gMG and confirming safety and tolerability after a single dose of NMD670 in patients.

NMD670 has been granted Orphan Drug Designation by the US FDA for treatment of gMG, and NMD Pharma has raised ~€155 million from investors including Novo Holdings, Lundbeckfonden BioCapital, INKEF Capital, Roche Venture Fund, and Jeito Capital.

Late-stage biotech Minoryx Therapeutics announced that results from its compassionate use study of leriglitazone (NEZGLYAL) for treatment of progressive cerebral adrenoleukodystrophy (cALD) in adult male patients have been published in the peer-reviewed journal Brain.

The study was led by Dr Fanny Mochel as part of an Early Access programme through the French national drug agency (ANSM) that allows for the use of innovative treatments with favourable safety profiles under a Compassionate Access Authorization protocol (ATU)2.

cALD is a fatal neurodegenerative disorder characterised by growing, demyelinating brain lesions, with death typically occurring within three to four years of onset. The 13 adult male participants in the study were either awaiting haematopoietic stem cell transplantation (HSCT) or ineligible for HSCT, only treatment currently available for cALD patients.

Leriglitazone is Minoryx Therapeutics’s novel orally bioavailable and selective PPAR gamma agonist with a potential first-in-class and best-in-class profile for CNS diseases. It is being developed to treat X-linked adrenoleukodystrophy (X-ALD) and other orphan CNS diseases and has shown robust preclinical proof-of-concept in animal models of multiple diseases by modulating pathways leading to mitochondrial dysfunction, oxidative stress, neuroinflammation, demyelination, and axonal degeneration.

Among the 13 patients treated with leriglitazone, the disease stabilised clinically and in radiological tests in 10 patients through up to two years of follow-up. Five patients that had originally presented with gadolinium enhancement (active neuroinflammation) lesions in the corticospinal tract all became gadolinium negative. Moreover, plasma neurofilament light chain levels (a biomarker for neurodegeneration) stabilised in all 10 patients and correlated with lesion load.

Leriglitazone was well tolerated in all patients, with minimal weight gain in most patients and moderate leg oedema in only two patients.

In consultation and alignment with the US FDA, Minoryx has launched a phase 3 clinical trial (CALYX5) in patients with adult progressive cALD that have a profile similar to those treated at Hôpital Universitaire La Pitié-Salpêtrière. CALYX is currently recruiting adult patients with progressive cALD in the US, Brazil, and Argentina.

In Europe, NEZGLYAL is exclusively licensed to Neuraxpharm.

Clinical stage biotech Moonlake Immunotherapeutics has announced the successful outcome of its end-of-Phase 2 interactions with both the US FDA and the European Medicines Agency (EMA), both regulatory bodies unanimously supporting the company’s proposed approach to advance its Phase 3 trial of Nanobody sonelokimab in psoriatic arthritis (PsA).

PsA is a chronic and progressive inflammatory arthritis associated with psoriasis, primarily affecting the peripheral joints. The clinical features of PsA are diverse, involving pain, swelling, and stiffness of the joints, which can result in restricted mobility and fatigue. PsA occurs in up to 30% of patients with psoriasis, most commonly those aged between 30 and 60 years.

The Phase 3 programme, named IZAR, is expected to enrol around 1,500 patients and, in combination with data from the Phase 2 ARGO trial, is designed to support both a Biologics License Application (BLA) and EU Marketing Authorization Application. Two global, randomised, double blind, placebo-controlled trials are planned (IZAR-1 and IZAR-2) to evaluate the efficacy and safety of Nanobody sonelokimab over one year.

Nanobodies represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies (VHH).

IZAR-1 will enrol a biologic naïve population and include an evaluation of radiographic progression, while IZAR-2 will enrol a TNF-IR population and will be the first trial to include a risankizumab active reference arm. The IZAR programme will assess a 60 mg sonelokimab dose, as well as a 120 mg sonelokimab dose.

Both trials will also include a range of secondary endpoints reflecting the multiple disease manifestations characteristic of PsA, including skin and nail outcomes, multidomain endpoints, and patient-reported outcome measures such as pain and quality of life assessments.

Sonelokimab is being assessed in two lead indications, HS and PsA, and the company is pursuing other indications in dermatology and rheumatology. For PsA, Phase 3 initiation is anticipated in Q4 2024.

The US FDA granted accelerated approval of Ipsen’s Iqirvo (elafibranor) for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have inadequate response to UDCA or as a monotherapy in patients unable to tolerate UDCA.

PBC is a rare, autoimmune, cholestatic liver disease, impacting approximately 100,000 people in the US, with about 90% of patients women between the ages of 35 and 65.

Iqirvo (elafibranor) 80 mg tablets are the first new treatment for PBC in almost a decade and the first in the peroxisome proliferator-activated receptor (PPAR) agonist class. Its therapeutic effects include inhibition of bile acid synthesis through activation of PPAR-alpha and PPAR-delta.

Approval was based on positive results from the pivotal Phase 3 ELATIVE clinical trial, presented as late-breaking data at AASLD 2023 and published in the New England Journal of Medicine, demonstrated that 13 times more patients had a rapid and sustained biochemical response with Iqirvo (51%) versus UDCA alone (4%) at 52 weeks and as early as week 4.

This indication is approved under accelerated approval based on reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated.

US approval of Iqirvo establishes Ipsen as a leader in the treatment of rare cholestatic liver diseases.

Iqirvo has been submitted to the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), seeking authorisation for PBC, with final EMA and MHRA regulatory decisions anticipated in the second half of 2024.