Source : 'The Pink Sheet'
If you thought COVID-19 convalescent plasma was yesterday’s news, think again. Results from studies of the treatment may have been disappointing so far, but the European Commission believes there is mileage in it yet – so much so that it is sinking €4m ($4.7m) into a new project called SUPPORT-E to look into whether it can be an effective and safe treatment for coronavirus patients.
SUPPORT-E, which is led by the European Blood Alliance (EBA), brings together 12 major research establishments and clinical centers from six EU countries, Switzerland and the UK and will coordinate and enable clinical studies on COVID-19 convalescent plasma (CCP) transfusion across Europe.
CCP has shown early indications of efficacy and an apparent very low incidence of adverse reactions, the commission noted. “However, experts agree that more evidence on efficacy is needed, in particular on the optimal treatment protocol. Thus, randomized controlled clinical trials are required to provide the highest quality of evidence of efficacy and safety.”
The project “will help not only determine safety and efficacy, but also to better understand which patients should be transfused and how, as well as how the donations should be tested and selected to ensure the best treatment outcome,” it said. The project will aim to produce harmonized recommendations on CCP collection, testing and therapeutic use and “could help prepare for future epidemics.”
Funding for SUPPORT-E is coming from the Horizon 2020 research and innovation program, as part of the commission’s €1bn pledge for coronavirus research and innovation that was announced in May.
Another potential treatment, InflaRx N.V.’s IFX-1, has just begun the global Phase III part of the German company’s Phase II/III clinical trial in people with severe COVID-19-induced pneumonia. The first clinical site has started up in the Netherlands, and the German regulatory body, the Paul Ehrlich-Institut, has approved the Phase III trial there.
IFX-1 is a first-in-class monoclonal anti-human complement factor C5a antibody that the company says is highly effective in blocking the biological activity of C5a and demonstrates high selectivity towards its target. Complement C5a is a powerful inflammatory mediator involved in the progression of a wide range of autoimmune and other inflammatory diseases.
The randomized, double-blind, placebo-controlled Phase III study will enroll about 360 early intubated, critically ill patients across sites in the US, the EU, South America and other regions. An interim analysis is planned after 180 patients have been enrolled, with the potential for an early stop for efficacy or futility. InflaRx said in July that data from the initial exploratory Phase II part of the study suggested a “positive impact” on the all-cause mortality rate and other endpoints. ("Coronavirus Notebook Vaccine Pooling WHOs Law Lab The Role Of The Llama" "Pink Sheet" )
Many existing therapeutics are being repurposed for potential use in treating COVID-19. The Swiss firm Relief Therapeutics Holding AG and NeuroRx, Inc. of the US are developing aviptadil, a patented synthetic form of vasoactive intestinal peptide (VIP), for the treatment of COVID-19-induced acute respiratory distress syndrome (ARDS) and are expecting top-line results from US Phase IIb/III trials early in the fourth quarter of this year.
Aviptadil is already marketed (in combination with phentolamine) in Europe for the treatment of erectile dysfunction. NeuroRx noted that ARDS was caused by a cytokine storm released in response to viral particles and said that VIP had been shown to have potent anti-cytokine effects in animal models and Phase I and II clinical trials.
Relief said aviptadil was “believed to be the first COVID-19 therapeutic to demonstrate the ability to block replication of the SARS-CoV-2 virus in human lung cells and monocytes, while also preventing synthesis of cytokines in the lung.”
Since July 2020, severe coronavirus patients have been treated with the drug under a US Food and Drug Administration emergency use investigational new drug (IND) authorization as well as an expanded access protocol authorization for the treatment of respiratory failure in COVID-19, the company noted. The product has US orphan drug status for ARDS, pulmonary hypertension and sarcoidosis.
Relief believes it has sufficient funds to complete the two US COVID-19 trials underway and is now preparing for European clinical trials of the drug in this indication.
On the vaccines front, the UK biotech firm Emergex Vaccines Holding Ltd says it expects to begin clinical trials of its first COVID-19 vaccine candidate in the fourth quarter of 2020, using a new Class I major histocompatibility complex (MHC) expression library for SARS-CoV-2 infected cells that was developed with George Mason University in the US.
The company is developing second-generation “set point” vaccines designed to generate a lasting and safe cellular immune response by programming CD8+ T-cells to rapidly recognize and respond to pathogens. It said this approach was intended to provide effective prevention of disease while eliminating the allergic, autoimmune or antibody mediated side effects associated with traditional vaccines.
“It is increasingly clear that T-cell responses to SARS-Cov-2 are the major if not dominant factor in the immune response to COVID-19 infection, and a vaccine which can safely and effectively harness this response could be critical to controlling the pandemic,” said Emergex’s CEO and co-founder, Thomas Rademacher. “Studies on T-cell memory recall to predicted peptides in convalescent COVID-19 individuals have inferred the presence of a strong T-cell response in these patients,” he noted.
Emergex is also developing set point vaccines for other health threats such as Dengue fever, Zika, Ebola, pandemic flu and serious intra-cellular bacterial infections.
On the global scale, the Access to COVID-19 Tools (ACT) Accelerator, an initiative intended to support the development and equitable distribution of vaccines, treatments and diagnostics, has outlined its immediate priorities for the September to December 2020 period.
The Facilitation Council of the ACT Accelerator held its first meeting on 10 September, at which it was stressed that $35bn was still needed if the initiative was to achieve its aim of producing two billion doses of vaccines by the end of 2021, 245 million courses of therapeutics by mid-2021, and 500 million tests, also by mid-2021. ("Coronavirus Notebook EMA Expects First Vaccine Efficacy Data Soon ACTAccelerator Needs Urgent Fun" "Pink Sheet" )
A presentation at the meeting that has just been published said the project’s immediate priorities in the vaccines area were to add one to five new candidates to its portfolio “based on imminent readouts” and to negotiate new deals with manufacturers “based on imminent Phase II/III results.” Country preparedness to deploy vaccines as soon as possible after they became available should be stepped up, the meeting heard.
In the therapeutics field, the near-term aim is to evaluate new monoclonal antibodies and antivirals, and to “select molecules for the first wave of manufacturing capacity reservations.” Three to five further market interventions are to be launched for repurposed medicines, and the rollout of dexamethasone will be scaled up.
More generally, the ACT Accelerator will put into operation its vaccines allocation mechanism and finalize the mechanism for allocating therapeutics. 10-15 country pilots will be launched to “test and refine the overall approach," while private sector capacity will be mapped and matched to identified public health needs.
By Ian Schofield