This week in clinical trials: 29th January to 2nd February

Continuing our weekly clinical trial round-ups, here we look at developments in life sciences research and development announced during the week of 29^th January to 2^nd February, from early-stage onwards. During that week, January came to a close with a flurry of announcements. There was news in rare orphan disease Mycosis Fungoides and prostate cancer trial data presented at ASCO-GU 2024, as well as developments in the allergy and autoimmune space and potential HIV vaccine candidates.

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

During the week of 29^th January to 2^nd February:

Clinical-stage oncology biopharma Vidac Pharma Holdings Plc announced that it had attained positive results from an interim analysis of its Phase 2a study of lead drug candidate VDA-1102 in Mycosis Fungoides (MF), a form of Cutaneous T-Cell Lymphoma (CTCL), a rare, orphan disease.

The interim analysis of 50% of subjects showed an Objective response Rate (ORR) of 56%, with 22% complete response (CR), and 34% partial response seen within eight to 12 weeks – favourable results compared to the standard care of mechlorethamine, which has a 13% CR and a longer median response time of 26 weeks.

There is now hope for fast-track regulatory processing, the data from the open-label within-subject placebo-controlled study providing further signs of the efficacy and safety of Vidac’s family of non-toxic small molecules in treating cancer. Full-population interim results are expected in Q2, with final results in Q4.

Vidac is developing a new technology that reverses abnormal metabolism of cancer cells – the Warburg effect - by preventing the Hexokinase 2 (HK2) enzyme from blocking the VDAC mitochondrial relay channels. The company’s lead drug candidate VDA-1102 is also at clinical development stage for patients with actinic keratosis (AK), and a second Phase 2b study is soon to launch in this.

At ASCO-GU Cancers Symposium 2024, Finnish pharma company Orion presented additional data from the ongoing Phase 2 CYPIDES trial evaluating the safety and efficacy of ODM-208 (or MK-5684), its investigational oral CYP11A1 inhibitor, in heavily pre-treated patients with metastatic castration-resistant prostate cancer (mCRPC) with and without AR-LBD mutations. 

Data published previously had focused on patients with androgen receptor gene (AR) ligand-binding-domain (LBD) mutations, and this new data reports initial results in an extension cohort of mainly AR-LBD wild-type patients combined with previously reported phase 2 data (AR-LBD mutation-positive only).

Prostate cancer continues to be regulated by steroid hormones, even in castration-resistant disease. Data from the Phase 2 CYPIDES trial suggests that ODM-208/MK-5684 potently inhibits all steroid-hormone biosynthesis with observed anti-tumour activity in a heavily pre-treated mCRPC population, especially in patients with AR-LBD mutations. 

At data cut-off, a total of 134 previously treated mCRPC patients received 5 mg of ODM-208/MK-5684 twice a day with glucocorticoid/mineralocorticoid replacement and ongoing androgen-deprivation therapy. Of the total, 66 patients had AR-LBD mutation and 68 were AR-LBD wild-type. PSA (prostate-specific antigen) responses occurred in men without AR-LBD mutations, but were more frequent in those with such mutations. A decrease in PSA levels of 50% or more occurred in 55.6% of patients with AR- LBD mutation and in 16.7% of AR-wild-type patients. 

Results on other endpoints are not yet mature and will be reported later. Phase 3 studies are now ongoing.

Primary results from the landmark SEPTA trial, with over 2,000 racially and ethinically diverse biopsied men recruited in the US and Canada, were presented at the ASCO-GU Cancers Symposium by Prof Scott Eggener, Professor of Surgery and Radiology, vice chair of Urology, and co-director of the UChicago Medicine High-Risk and Advanced Prostate Cancer Clinic (UCHAP) at the University of Chicago.

The study has found that use of blood-based biomarker Stockholm3 is more accurate and can avoid up to half of unnecessary biopsies compared to current clinical practice, with findings similar across all racial and ethnic groups.

Stockholm3 incorporates plasma proteins, a polygenetic risk score, and clinical variables, and was developed by researchers at Sweden’s Karolinska Institute. The SEPTA trial was carried out at 17 US and Canadian sites and it the first prostate cancer trial where the majority of patients are from historically underrepresented minorities. Of 2,129 recruited men, 1,160 were either Asian, Black, or Hispanic.

Prostate cancer is the most common form of cancer in American men. In 2024, it is estimated that 300,000 men will be diagnosed with, and 35,000 will die from, prostate cancer in the United States alone. Early detection and reduced overdiagnosis are crucial for improved treatment outcomes, decreased mortality, and better use of healthcare resources. 

Meanwhile, worldwide, prostate cancer is the second most common male cancer, and the fifth leading cause of cancer related death in men. According to the World Health Organization (WHO), 1.4 million men were diagnosed with prostate cancer and 375,000 deaths were reported in 2020. Incidence of prostate cancer is expected to increase by 70% until 2040, driven by an aging population.

Revolo Biotherapeutics announced that it has been granted Orphan Drug Designation (ODD) by the US FDA for first-in-class ‘1104, an immune-resetting peptide, as a potential treatment for eosinophilic oesophagitis (EoE).

‘1104 activates regulatory immune cells (T regulatory cells), and restores immune system balance, mitigating chronic inflammation without compromising immune response.

EoE is a chronic, allergic inflammatory disease that is characterised by accumulation of eosinophils in the lining of the oesophagus. If not effectively treated, patients with EoE may have difficulty swallowing, chronic pain, malnutrition, and weight loss.

The FDA grants ODD status to support development and evaluation of potential new medicines intended for the treatment, diagnosis, or prevention of rare disease or disorders that affect fewer than 200,000 people in the US.

Based on previously reported positive Phase 2s study results, Revolo – which develops therapies that reset the immune system to achieve superior long-term remission for patients with autoimmune and allergic disease – plans to initiate a Phase 2b study later this year, which will evaluate higher dose levels of ‘1104 and a longer duration of therapy.

Revolo also has in development ‘1805, a modified analogue of a key protein in immune function, which is nearing initiation of Phase 2 clinical trial in patients with moderate-to-severe rheumatoid arthritis, and a Phase 2a clinical trial for an additional autoimmune indication.

Uvax Bio, a privately held clinical-stage vaccine company spun out from Scripps Research, announced that it has started a Phase 1 clinical trial to evaluate its novel protein nanoparticle HIV-1 vaccine candidates, UVAX-1107 and UVAX-1197, and that the first participant from a cohort of healthy volunteers in Australia has been dosed.

The vaccine candidates use Uvax’s 1c-SApNP platform, developed by Dr Jiang Zhu of Scripps Research, which enables production of virus-like protein particles that can display 20-60 stabilised antigens targeting a wide range of viral and bacterial diseases.

The Joint United Nations Programme on HIV/AIDS estimates that 39 million people worldwide are currently living with HIV, and that 1.3 million people became newly infected with HIV in 2022 alone. According to the latest estimates from the Centers for Disease Control and Prevention (CDCP), in the US there have been approximately 32,100 new HIV infections recently.

In addition to evaluating the safety and immunogenicity of UVAX-1107 and UVAX-1197, the Phase 1 trial will determine if either vaccine or a combination of both produces optimal immunological response.

Uvax is expecting to report topline data from the Phase 1 trial in Q4 this year.