3rd to 7th June – This week in clinical trials

This week in clinical trials

In this instalment of our clinical trials round-ups, we look at life sciences research and development announced during the week of 3rd to 7th June, from early-stage onwards.

During that week, pharmaphorum news was on the pulse of two big conferences: ASCO and BIO International, both of which our editor-in-chief Jonah Comstock was live on site for, including live blogging BIO.

From the revelation that Gilead Sciences’ bid to extend the uses of TROP2-directed Trodelvy into lung cancer currently rests on the results of its EVOKE-01 study, to an artificial intelligence-based tool showing impressive results in raising colorectal cancer screening rates in underserved populations, and from GSK’s increasing confidence that its anti-BCMA drug Blenrep could be returned to the US market (be sure to check out Comstock’s video interview with Dr Suzanne Trudel on this) to three of AstraZeneca’s top cancer drugs being on display – EGFR inhibitor Tagrisso (osimertinib), PD-L1 inhibitor Imfinzi (durvalumab), and Daiichi Sankyo-partnered HER2 antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan), with new data that could expand their use and drive sales – the 3rd through 7th June was a big week, to say the least, when it comes to industry news. And that includes the below.

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

Key Takeaways

  • uniQure announces FDA grants RMAT designation for AMT-130 for Huntington’s disease
  • Takeda shares late-breaking Phase 2 TAK-861 data for narcolepsy type 1 at SLEEP
  • Otsuka announces results from Ionis’ Phase 3 OASIS-HAE + OASISplus studies of donidalorsen for hereditary angioedema
  • CatalYm announces positive GDFather Phase 1/2a trial at ASCO
  • Agios announces Mitapivat meets endpoints in ENERGIZE-T study in transfusion-dependent alpha- or beta-thalassaemia
  • Transgene announces first patient enrolled in Ph II part of randomised Phase 1/2 trial in TG4050 for head and neck cancer
  • QuellTx advances QEL-001 CAR-Treg cell therapy into efficacy cohort of LIBERATE Ph 1/2 in liver transplant


During the week of 3rd to 7th June:

uniQure announces FDA grants RMAT designation for AMT-130 for Huntington’s disease

uniQure announced that the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to AMT-130, a gene therapy in development for Huntington’s disease – the first ever investigational therapy for the disease to receive such designation.

Huntington’s disease is a rare, inherited neurodegenerative disorder that leads to motor symptoms including chorea, behavioural abnormalities, and cognitive decline resulting in progressive physical and mental deterioration. The disease is an autosomal dominant condition with a disease-causing CAG repeat expansion in the first exon of the huntingtin gene that leads to the production and aggregation of abnormal protein in the brain.

RMAT designation was created as part of the 21st Century Cures Act to expedite the development and review processes of regenerative medicine therapies. A regenerative medicine therapy can be eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious condition, and if preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such a condition. Receiving RMAT designation offers sponsor companies all the benefits of the fast track and breakthrough therapy designation programmes, allowing for early, close, and frequent interactions with the FDA.

With AMT-130, the designation follows the FDA’s review of interim Phase 1/2 clinical data announced in December 2023 and is based on an analysis comparing the 24-month data to a non-concurrent criteria-matched natural history cohort.

By mid-year, uniQure expects to provide updated interim data from the ongoing Phase 1/2 US and European studies of AMT-130, including up to three years of follow-up on 29 treated patients, 21 of which will have been followed for at least two years.

In October 2023, Netherlands-based uniQure had announced it would shed 20% of its workforce, around 114 jobs, and slash its R&D projects in an effort to extend its cash reserves, prioritising the development of AMT-130 and a handful of other projects.

Takeda shares late-breaking Phase 2 TAK-861 data for narcolepsy type 1 at SLEEP

Meanwhile, Takeda shared late-breaking Phase 2b data for TAK-861, a homegrown oral orexin receptor 2 (OX2R) agonist and a new approach to combatting narcolepsy type 1 (NT1) that is designed to address the underlying pathophysiology of the disease at 38th annual meeting of the American Academy of Sleep Medicine and the Sleep Research Society (SLEEP) meeting.

NT1 is a chronic, rare neurological central disorder of hypersomnolence caused by a significant loss of orexin neurons, resulting in low levels of orexin neuropeptides in the brain and cerebrospinal fluid. No currently approved treatments target the underlying pathophysiology of NT1. People with NT1 suffer from excessive daytime sleepiness (EDS), cataplexy (sudden loss of muscle tone), disrupted nighttime sleep, hypnagogic and hypnopompic hallucinations, and sleep paralysis.

The randomised, double-blind, placebo-controlled, multiple dose Phase 2b trial of 112 patients demonstrated statistically significant and clinically meaningful improvements across primary and all secondary endpoints up to 8 weeks.

The primary endpoint demonstrated statistically significant and clinically meaningful increased sleep latency on the Maintenance of Wakefulness Test (MWT) versus placebo across all doses, while consistent results were achieved in the key secondary endpoints including the Epworth Sleepiness Scale (ESS) and Weekly Cataplexy Rate (WCR), demonstrating significantly improved subjective measures of sleepiness and cataplexy (sudden loss of muscle tone) frequency versus placebo that were also sustained over 8 weeks.

The majority of the participants who completed the trial enrolled in the long-term extension (LTE) study with some patients reaching one year of treatment.

Based on these results, and in consultation with global health authorities, Takeda plans to initiate global Phase 3 trials of TAK-861 in NT1 in the first half of its fiscal year 2024. The Phase 2b data also supported the recent Breakthrough Therapy designation for TAK-861 for the treatment of EDS in NT1 from the US Food and Drug Administration (FDA).

Otsuka announces results from Ionis’ Phase 3 OASIS-HAE + OASISplus studies of donidalorsen for hereditary angioedema

Otsuka Pharmaceutical Europe (PDF) announced new results from Ionis’ Phase 3 OASIS-HAE and OASISplus studies of donidalorsen (80 mg) via subcutaneous injection every four or eight weeks in people with hereditary angioedema (HAE).

The results were presented in three late-breaking oral presentations at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Annual Meeting in Valencia, Spain (31st May – 3rd June 2024), with the OASIS-HAE results having been published in The New England Journal of Medicine (NEJM) on Friday 31st May.

HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face, and/or throat. Donidalorsen is an investigational RNA-targeted prophylactic medicine designed to reduce the production of prekallikrein (PKK), interrupting the pathway that leads to HAE attacks.

Results from the OASIS-HAE study, OASISplus open-label extension (OLE) cohort, and OASISplus switch cohort all demonstrated reductions in mean monthly HAE attack rates following treatment with donidalorsen, when compared to either placebo or baseline.

Donidalorsen has received Orphan Drug Designation (ODD) in the EU.

CatalYm announces positive GDFather Phase 1/2a trial at ASCO

CatalYm announced positive results from it GDFather Phase 1/2a trial (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 1/2a), highlighting that the visugromab/nivolumab combination treatment investigated achieves deep and durable anti-tumoural activity, including multiple complete responses in late- to last-line patients with metastatic non-squamous non-small cell lung cancer (NSCLC), urothelial cancer (UC), and hepatocellular carcinoma (HCC).

GDF-15 impedes T-cell recruitment into tumour microenvironments, which is a significant obstacle to standard treatments and immunotherapies like checkpoint inhibitors, while visugromab counters these suppressive mechanisms to facilitate immune cell infiltration into tumours.

The Phase 2a GDFATHER-2 programme was initiated in March 2022. The ongoing study consists of two segments with up to seven cohorts and is expected to enrol over 200 patients in various cohorts. Based on a previous positive readout presented at the ESMO IO Congress in December 2023, CatalYm is in preparations to launch randomised, controlled studies in several major cancer indications in combination with checkpoint inhibitors and standard-of-care in first- and second-line treatment in the first half of 2025.

Agios announces Mitapivat meets primary and secondary endpoints in ENERGIZE-T study in transfusion-dependent alpha- or beta-thalassaemia

Agios Pharmaceuticals Inc, which specialises in cellular metabolism and pyruvate kinase (PK) activation therapies for rare diseases, announced that the global Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent (TD) alpha- or beta-thalassaemia achieved its primary endpoint of demonstrating a statistically significant transfusion reduction response compared to placebo.

Statistical significance was also achieved for all key secondary endpoints evaluating additional measures of reduction of transfusion burden compared to placebo.

ENERGIZE-T is the first Phase 3 study to demonstrate efficacy of an oral, disease-modifying treatment for transfusion-dependent alpha- and beta-thalassaemia. A total of 258 patients were enrolled in the study, with 171 randomised to mitapivat 100 mg twice-daily (BID) and 87 randomised to matched placebo. 155 patients in the mitapivat arm and 83 patients in the placebo arm completed the 48-week double-blind period of the study.

With the positive data generated in the Phase 3 ENERGIZE-T and ENERGIZE studies of mitapivat in patients with alpha- or beta- thalassemia regardless of transfusion needs, the company intends to submit a marketing application for mitapivat (PYRUKYND) in the US by the end of 2024 based on all available data from both studies. The company also plans to submit marketing applications in Europe and the Gulf Cooperation Council (GCC) countries.

Data from the Phase 3 ENERGIZE study of mitapivat in non-transfusion-dependent thalassemia will be presented at the European Hematology Association 2024 Hybrid Congress in a plenary session on 15th June.

Transgene announces first patient enrolled in Ph II part of randomised Phase 1/2 trial in TG4050 for head and neck cancer

Biotech Transgene (PDF), which designs and develops virus-based immunotherapies for the treatment of cancer, announced that patient screening and enrolment has been initiated for the Phase II part of its international, randomised Phase 1/2 trial to evaluate lead cancer vaccine TG4050 – being jointly developed with NEC – in head and neck cancer, with an overall sample size of approximately 80 patients.

Promising TG4050 Phase I data presented at AACR 2024 showed strong immunogenicity, persistent cellular immune response, and signs of clinical benefit for patients. At the time of the analysis, only patients in the control arm had relapsed, while all patients who received TG4050 were disease-free. This Phase II part will continue investigating single-agent TG4050 in patients with newly diagnosed, locoregionally advanced, HPV-negative, squamous cell carcinoma of the head and neck (SCCHN) in the adjuvant setting following completion of surgery and chemoradiotherapy.

Although some advancements in the treatment of SCCHN have been made, there remains a significant medical need for these patients, including in the adjuvant setting. With the current standard of care, 30% to 40% of patients are expected to relapse within 24 months following surgery and adjuvant therapy. Despite completed Phase III trials, immune checkpoint inhibitors have yet to demonstrate significant benefits for these patients.

TG4050 is based on Transgene’s (PDF, Fr) myvac (MVA – Modified Vaccinia Ankara) viral vector platform and NEC’s AI capabilities for the identification and prediction of immunogenic neoantigens in individual patients.

The last patient enrolment for the Phase II part is expected in Q4 of 2025.

QuellTx advances QEL-001 CAR-Treg cell therapy into efficacy cohort of LIBERATE Ph ½ in liver transplant

As presented at the American Transplant Congress, Quell Therapeutics has announced advancement of QEL-001, its multi-modular engineered CAR-Treg cell therapy, into the efficacy cohort of the LIBERATE Phase 1/2 trial in liver transplant patients.

Quell develops engineered T-regulatory (Treg) cell therapies for serious medical conditions driven by the immune system. The LIBERATE trial is a multi-centre, first-in-human, open-label, single-arm Phase 1/2 study evaluating the safety and efficacy of QEL-001 in approximately 18 HLA-A2 mismatched liver transplant patients, one to five years post-liver transplant, at sites in the UK, Belgium, and Spain.

The decision to advance the LIBERATE trial follows the successful completion of dosing in the initial safety cohort and subsequent approval by the trial’s independent Data Safety and Monitoring Board (DSMB) following its review of the clinical data.

The presentation by Prof Alberto Sánchez-Fueyo, Professor of Hepatology and Academic Director of the Institute of Liver Studies at Kings College London, as well as co-founder of Quell, concluded that Tregs from liver transplant patients can be isolated and expanded to generate engineered CAR-Tregs with improved safety and therapeutic characteristics for clinical use.

Engraftment and trafficking of QEL-001 to the liver allograft and persistence of infused cells for up to six months in the periphery post infusion was confirmed and the initial data supports further investigation of QEL-001 CAR-Treg therapy in HLA-A2 mismatched liver transplant patients to induce operational tolerance and decrease the side-effects of immunosuppressive (IS) therapy.

Approximately 15,000 patients receive new liver transplants in the US and EU5 each year and the standard of care for liver transplant patients is to receive systemic immunosuppression for the rest of their lives.

Quell will now proceed with evaluating QEL-001 in the efficacy cohort of liver transplant patients, which will assess the induction of tolerance at two and 12 months after full withdrawal of IS therapy. The ability to wean patients off IS at the two-month evaluation point is expected to be highly predictive of achieving longer-term operational tolerance.