Expedited UK regulatory acceptance to commence Phase II study in COVID-19
LEEDS, UK — 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics (LBP), today announces that the Company has received expedited acceptance from the UK Medicines and Healthcare products Regulatory Agency (MHRA) to commence a Phase II study of MRx-4DP0004 in patients with COVID-19.
COVID-19, caused by infection with SARS-CoV-2, has emerged as a significant global threat and is placing a huge burden on healthcare systems worldwide. Although many patients exhibit only mild symptoms, approximately 15-20% develop severe disease requiring hospitalisation and oxygen support. Approximately 5% of all patients require admission to an intensive care unit (ICU).
Accumulating evidence suggests that the high mortality rate of COVID-19 may be due to the hyper-inflammatory response and cytokine storm syndrome caused by uncontrolled activation of the immune system and targeted immunomodulation may be beneficial in these patients1.
There is an urgent need for a safe and effective therapy to prevent and treat the severe inflammatory symptoms of COVID-19, and to alleviate the significant burden on ICUs in hospitals worldwide.
MRx-4DP0004 is an orally administered, single-strain Live Biotherapeutic currently in a Phase I/II clinical trial for the treatment of patients with partly-controlled asthma. To date, 20 patients have been dosed, with no drug related serious adverse events. In preclinical studies the Company has previously shown that MRx-4DP0004 is able to significantly reduce lung inflammation and impact particular immune cell types and pathways which have more recently been implicated in the hyperinflammatory response to SARS-CoV-2 infection.
In a preclinical model of severe asthma, MRx-4DP0004 significantly reduced airway inflammation, including a reduction in the number of neutrophils, eosinophils and activated dendritic cells. The LBP candidate also reduced pro-inflammatory cytokines in lung tissues2. The systemic immunomodulatory effects of MRx-4DP0004 have also been demonstrated in additional preclinical models of inflammatory diseases including multiple sclerosis and rheumatoid arthritis.
The randomised, double-blind, placebo-controlled Phase II study will evaluate the efficacy and safety of MRx-4DP0004, in addition to standard-of-care in up to 90 patients hospitalised with symptoms indicative of COVID-19. Eligible participants will be randomised 2:1 to receive 14 days of treatment with either MRx-4DP0004 or placebo (two capsules twice daily). Participants will be monitored daily throughout the treatment period for improvement or progression of COVID-19 symptoms and adverse events. Following completion of the treatment period, participants will be followed-up at approximately 14 and 28 days post treatment. Patients will be recruited at sites across the UK.
The primary endpoint will be the mean change in clinical status score as measured by the WHO Ordinal Scale for Clinical Improvement. Secondary endpoints include safety and tolerability as well as a suite of additional measures of clinical efficacy including the need for and duration of ventilation. Further information will be made available at clinicaltrials.gov in due course.
4D’s Chief Scientific Officer, Alex Stevenson, commented:
“Over the last month we have worked intensively with our clinical collaborators and the regulatory agencies to accelerate the assessment of MRx-4DP0004 in COVID-19 patients. C learly this is a fast moving and rapidly developing situation. As an integrated company we have manufacturing capability to provide drug and our key focus over the coming weeks will be initiating the trial as soon as possible. If MRx-4DP0004 is successful in this study it would represent a highly significant breakthrough in the global fight against the novel coronavirus pandemic.”
The study’s Lead Investigator, Dr. Dinesh Saralaya (Consultant Respiratory Physician and Associate Director of Research at Bradford Teaching Hospitals NHS Foundation Trust, and the National Institute for Health Research’s (NIHR) Clinical Lead for Respiratory industry studies), commented:
“The COVID-19 pandemic presents an unprecedented challenge to our healthcare systems and we desperately require the rapid development of new therapies to ease the burden on our intensive care units. Given the scale and urgency of the situation it is vitally important that we generate evidence to support the use of new candidates as quickly as possible, before these can be rolled out to patients who need them.”
He added: “As well as its appropriate mechanism of action, the highly favourable safety profile of MRx-4DP0004 makes it a particularly attractive candidate for COVID-19 patients, and may potentially allow us to prevent or delay their progression to requiring ventilation and intensive care.”
Founded in February 2014, 4D pharma is a world leader in the development of Live Biotherapeutics, a novel and emerging class of drugs, defined by the FDA as biological products that contain a live organism, such as a bacterium, that is applicable to the prevention, treatment or cure of a disease. 4D has developed a proprietary platform, MicroRx®, that rationally identifies Live Biotherapeutics based on a deep understanding of function and mechanism.
4D’s Live Biotherapeutic Products are orally delivered single strains of bacteria that are naturally found in the healthy human gut. The Company has five clinical studies in progress, namely a Phase II clinical study of BLAUTIX® in Irritable Bowel Syndrome (IBS), a Phase I/II study of MRx0518 in combination with KEYTRUDA® (pembrolizumab) in solid tumours, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumours, a Phase I study of MRx0518 in patients with pancreatic cancer and a Phase I/II study of MRx-4DP0004 in asthma. Preclinical-stage programmes include candidates for CNS disease such as Parkinson’s disease and other neurodegenerative conditions. The Company has a research collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, to discover and develop Live Biotherapeutics for vaccines.
For more information, refer to https://www.4dpharmaplc.com
MRx-4DP0004 is a single-strain Live Biotherapeutic in development for the treatment of asthma and COVID-19. It has demonstrated strong and significant efficacy in industry standard preclinical models of steroid-resistant severe asthma. MRx-4DP0004 was shown to reduce both neutrophils and eosinophils in prophylactic and therapeutic settings in vivo. The efficacy was also reflected in a reduction in histopathological lung inflammation, and specific subsets of T cells, dendritic cells and inflammatory cytokines.
4D is currently investigating MRx-4DP0004 in a Phase I/II study in patients with partly-controlled asthma. The study, taking place at sites across the UK and EU, is evaluating the safety and preliminary clinical efficacy of MRx-4DP0004 in addition to standard maintenance therapy such as inhaled corticosteroids (ICS) and long acting beta agonists (LABA), in up to 90 patients. For more information about the clinical study please visit https://clinicaltrials.gov/ct2/show/NCT03851250
The Company has received expedited acceptance from the MHRA to conduct a Phase II study of MRx-4DP0004 in up to 90 patients hospitalised with suspected or confirmed COVID-19.
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