Dapagliflozin Phase III Trial Launched for Severe COVID-19; BIO-11006 Achieves Phase 2a Primary Endpoint in ARDS

In the treatment of patients with coronavirus disease 2019 (COVID-19), in addition to using antiviral therapies to suppress viral replication and transmission, it is also crucial to manage complications arising in severe cases. For instance, multiple organ damage in many patients stems from cytokine storms triggered by factors such as viral infection. To mitigate excessive inflammatory responses in patients, IL-6 antibodies from Roche and Sanofi have been evaluated in Phase 3 clinical trials. Other anti-inflammatory therapies under investigation in clinical trials include AstraZeneca’s BTK inhibitor Calquence and Novartis/Incyte’s JAK inhibitor Jakafi.

Below, we will examine the research and development trends of other therapies targeting symptoms in critically ill patients.

Graphic by WuXi AppTec Content Team

AstraZeneca Initiates Phase 3 Clinical Trial to Evaluate the Efficacy of Dapagliflozin in Treating Patients with Severe COVID-19

On the 24th, AstraZeneca and Saint Luke’s Mid America Heart Institute jointly announced the initiation of a randomized, global Phase 3 clinical trial to evaluate the efficacy of the SGLT-2 inhibitor dapagliflozin (brand name Farxiga) in treating hospitalized COVID-19 patients at risk of developing severe complications, such as organ failure.

COVID-19 patients with underlying cardiac, renal, and metabolic conditions have a particularly poor prognosis, whereas extensive data from clinical trials indicate that dapagliflozin can provide benefits for patients with heart failure with reduced ejection fraction (HFrEF), chronic kidney disease, or type 2 diabetes.

The DARE-19 clinical trial will target COVID-19 patients with cardiovascular, metabolic, and renal disease risk factors to evaluate whether dapagliflozin can reduce the risk of disease progression, clinical complications, and death in this specific patient population.

Innovative Therapy for Acute Respiratory Distress Syndrome Achieves Primary Endpoint in Phase 2a Clinical Trial

On the 24th, Biomarck Pharmaceuticals announced that its investigational therapy, BIO-11006, met the primary endpoint in a Phase 2a clinical trial for the treatment of acute respiratory distress syndrome (ARDS). Demonstrating a favorable safety profile, the therapy reduced all-cause mortality by 43% in ARDS patients at 28 days post-treatment.

Globally, 3 million people are affected by ARDS annually. ARDS can be caused by various factors, including bacterial and viral pneumonia, sepsis, and more recently, COVID-19 infection. ARDS leads to widespread capillary leakage and inflammation in the lungs, which is a life-threatening condition. Apart from mechanical ventilation, treatment options for ARDS are limited, with mortality rates among ARDS patients approaching 40%.

▲Schematic diagram of BIO-11006 (Image source: Biomarck official website)

BIO-11006 is an innovative peptide composed of 10 amino acids, identical to the N-terminal 10-amino-acid sequence of the MARCKS protein, and can be administered via inhalation. The MARCKS protein is hyperphosphorylated in inflammatory cells and promotes their migration. BIO-11006 inhibits the phosphorylation of the MARCKS protein, thereby reducing the inflammation mediated by it.

This Phase 2a clinical trial included 38 patients with ARDS. The results demonstrated that BIO-11006 did not lead to a significant increase in serious adverse events and reduced all-cause mortality in ARDS patients at 28 days post-treatment.

“Based on these data, as well as the safety and efficacy profile of BIO-11006, we plan to advance this investigational therapy into Phase 3 clinical trials. We look forward to continuing our discussions with the FDA regarding the treatment of patients with COVID-19-associated ARDS, who currently lack effective therapeutic options beyond mechanical ventilation,” said Dr. Brian Dickson, Chief Executive Officer of Biomarck.

References:

[1] AstraZeneca and Saint Luke’s Mid America Heart Institute initiate Phase III DARE-19 trial with Farxiga in COVID-19 patients. Retrieved April 23, 2020, from https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/astrazeneca-and-saint-lukes-mid-america-heart-institute-initiate-phase-iii-dare-19-trial-with-farxiga-in-covid-19-patients.html

[2] Biomarck Announces, Phase 2a Clinical Trial Results of BIO-11006 for Acute Respiratory Distress Syndrome (ARDS). Retrieved April 23, 2020, from https://www.businesswire.com/news/home/20200423005540/en

Original Title: COVID-19 R&D Updates: Phase 3 Clinical Trial of Dapagliflozin for Severe Patients Initiated, Innovative Therapy for Acute Respiratory Distress Syndrome Reaches Phase 2a Clinical Endpoint

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