Watch Out for the Most Promising Therapies in the Pipeline in ARDS Market

Acute respiratory distress syndrome (ARDS) is a rapidly progressing condition that affects critically ill people. The major complication of ARDS is fluid leaking into the lungs, which makes breathing difficult or impossible. Shortness of breath, cough, and fever are among ARDS symptoms; in certain cases, high heart rates and rapid breathing have also been observed. Patients with ARDS may have chest pain, particularly during inhalation, and some may also have blue nails and lips owing to drastically reduced oxygen levels in the blood. Out of total COVID-19 cases, the critically ill patients—very few and ranging from 1–4%—constitute the potential pool for ARDS.

DelveInsight analysis shows there were approximately 1 million ARDS incident cases in the 7MM in 2021, with the US accounting for the highest number of incident cases. These cases are expected to increase by 2032 at a CAGR of 1.5% during the study period 2019–2032.

Acute respiratory distress syndrome is treated with supportive measures such as mechanical ventilation, prevention of stress ulcers and venous thromboembolism, nutritional assistance, and therapy of the underlying damage. Low tidal volume, strong positive end-expiratory pressure, and conservative fluid management may enhance results. Diagnosing and treating any underlying infections with antibiotics that target culture sensitivities is critical. Despite decades of study, ARDS treatment options are limited. The core of management is supportive care with mechanical ventilation. There are few ARDS therapies available in the ARDS market.

Other ARDS treatment options for patients include supplementary oxygen, prone posture, paralytics, fluid management, and a method known as positive end-expiratory pressure (PEEP) to help force fluid out of air sacs. These are used in conjunction with ongoing ARDS treatment of the initial illness or injury.

Because persons with ARDS have a reduced ability to fight infections in their lungs, they may acquire bacterial pneumonia throughout their illness. Antibiotics are used to treat infections. Supportive care, such as intravenous fluids or nourishment, may also be required.

The Food and Drug Administration granted an emergency use authorization (EUA) for the drug Actemra/RoActemra (tocilizumab for the ARDS treatment of hospitalized adults and pediatric patients (2 years of age and older) receiving systemic corticosteroids and requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation) (ECMO). Pluristem Therapeutics’ Expanded Access Program (EAP) uses its PLX-PAD cells to treat ARDS induced by COVID-19 outside of the current phase II COVID-19 research in the US was also authorized by the FDA. Current ARDS medications are only effective in treating ARDS-related inflammation; none treat reduced lung function.

However, the ARDS market is expected to grow positively due to the factors such as an increase in the incident pool, the anticipated entry of emerging therapies, among others, in the 7MM. The increase in ARDS market size is also a consequence of a rise in awareness and disease understanding.

As per our estimates, the ARDS market size in the 7MM was approximately USD 1,173.1 million in 2021, which is further expected to increase by 2032 at a CAGR of 10.31% for the study period (2019–2032).

Several molecules are being evaluated and investigated by leading pharmaceutical companies such as MediciNova, Edesa Biotech, Light Chain Biosciences, Boehringer Ingelheim, Genentech, Windtree Therapeutics, Biomarck Pharmaceuticals, Athersys, Healios, Direct Biologics, Biohaven Pharmaceutical, Arch Biopartners, APEPTICO Forschung und Entwicklung GmbH, Staidson (Beijing) Biopharmaceuticals, Veru, Mesoblast Limited, Avalo Therapeutics, Pluristem Therapeutics, ILTOO Pharma, and others to strengthen the ARDS pipeline, thereby raising the hope for an efficacious therapy soon.

The expected launch of emerging ARDS therapies, such as EB05 (Edesa Biotech/Light Chain Bio), DB-001 (Direct Biologics), BIO-11006 (BioMarck Pharmaceuticals), MultiStem (Athersys/Healios), Alteplase (Boehringer Ingelheim/Genentech), and Lucinactant (Windtree Therapeutics), and others shall further create a positive impact on the ARDS market.

Apart from the molecules mentioned above, BDB-001, Zavegepant, Metablok, Veru-111, PLX-PAD, among others, are the other pipeline ARDS therapies expected to enter the ARDS market in the coming years targeting the COVID-19-associated ARDS.Moreover, the uptake of potential emerging ARDS therapies with a better clinical profile is expected to be high since no drug is approved. Currently, several assets in the ARDS pipeline are in the late and middle stages of development.

Emering Therapies in the ARDS Market

Drug: DB-001

Company: Direct Biologics

Phase: Phase III

MoA: Immunosuppressants; Inflammation mediator modulators; Protein replacements

Special Designation: Regenerative Medicine Advanced Therapy (RMAT) (US)

Direct Biologics’ ExoFlo (DB-001) is an extracellular signal product extracted from human bone marrow mesenchymal stem or stromal cells (BM-MSCs) that comprises growth factors and extracellular vesicles such as exosomes. It delivers natural bioactive signals to people that reduce inflammation, guide cellular communication, and promote tissue healing. The FDA awarded ExoFlo a Regenerative Medicine Advanced Therapy (RMAT) designation in April 2022. In July 2022, the company began phase III testing of the ARDS drug for moderate-to-severe COVID-19 ARDS.

Drug: Remestemcel-L

Company: Mesoblast

Phase: Phase III

MoA: Cell replacements

Special Designation: Fast Track Designation (US)

Mesoblast’s Remestemcel-L is an experimental treatment that consists of culture-expanded MSCs generated from an unrelated donor’s bone marrow and is provided in a series of intravenous infusions. The therapy is thought to have immunomodulatory capabilities, allowing it to inhibit inflammatory processes. Remestemcel-L was recently granted Fast Track designation for SARS-COV-2 acute respiratory disease. In addition to the recently completed ARDS clinical trial, the FDA has directed Mesoblast to do additional clinical research in Covid-19 ARDS to support an emergency use authorization (EUA).

Drug: EB05

Company: Edesa Biotech/Light Chain Bio

Phase: Phase II/III

MoA: Toll-like receptor 4 antagonists

EB05 is an experimental monoclonal antibody that Edesa hopes might modulate the hyperactive and malfunctioning immune response associated with ARDS. The ARDS drug explicitly suppresses toll-like receptor 4 (TLR4) signaling, which is a key mediator of inflammation responsible for acute lung damage and is stimulated by SARS-CoV2, SARS-CoV1, and Influenza viruses. EB05 has been shown to be safe in two clinical investigations (>120 patients) and to be capable of blocking LPS-induced (TLR4 agonist) IL-6 production in humans. Health Canada granted the company permission to test EB05 as a rescue ARDS treatment for critically sick patients in the phase III part of phase II/III ARDS clinical trial research. While in the United States, the company is now in conversation with the FDA about the design of the final phase III protocol.

According to the company pipeline, the company is also looking into the potential of EB06, a monoclonal antibody candidate that binds directly and selectively to chemokine ligand 10 (CXCL10) and blocks its interaction with its receptors.

Drug: MultiStem

Company: Athersys/Healios

Phase: Phase II/III

MoA: Cell replacements

Special Designation: Fast Track Designation (US), RMAT Designation (US)

MultiStem, also known as AMI MultiStem, HLCM 051, and PF-05285401, is a patented regenerative product that can promote tissue repair and healing in a variety of ways, including the production of multiple therapeutic factors in response to signals of inflammation and tissue damage, as well as the restoration of immune system balance. Athersys is developing MultiStem, which is currently in the phase II/III stage for the treatment of COVID-19-induced ARDS. The Food and Drug Administration granted Athersys Fast Track status for their ARDS clinical trial assessing MultiStem cell therapy for ARDS treatment. In addition, the FDA granted RMAT Designation to MultiStem Cell Therapy for ARDS treatment in September 2020. The company is presently recruiting patients in a key phase II/III research to test MultiStem cell treatment in patients with Covid-19-induced ARDS.

Drug: Alteplase

Company: Boehringer Ingelheim/Genentech

Phase: Phase II/III

MoA: Fibrinolytic agents; Plasminogen activator stimulants; Plasminogen activators

Alteplase is the sole approved thrombolytic (blood clot-dissolving) medicine for acute ischemic stroke therapy, and it is utilized in many stroke centers. It’s also used to treat acute myocardial infarction, acute large pulmonary embolism, and catheter clearance owing to thrombotic occlusion (indications vary across countries). Boehringer Ingelheim markets Alteplase as Actilyse in countries other than the United States and Canada. Meanwhile, Genentech markets it in the United States and Canada. The drug is currently being tested in phase II/III (TRISTARDS) ARDS clinical trials for the treatment of Covid-19 ARDS.

Drug: BIO-11006 

Company: BioMarck Pharmaceuticals

Phase: Phase II

MoA: Myristoylated alanine-rich C kinase substrate inhibitors

BIO-11006, BioMarck Pharmaceuticals’ lead drug, is being developed for the treatment of ARDS. BIO-11006, developed by Biomarck, is a novel, highly soluble, patented 10 amino acid peptide. It is being developed to precisely target the MARCKS protein to impede cancer cell division and motility as a MARCKS (Myristoylated alanine-rich C kinase substrate) inhibitor. Furthermore, it is a water-soluble, stable aerosolized anti-MARCKS peptide inhalation solution that involves aerosolized administration of either the active medicine or placebo using the “Aeroneb Pro nebulizer” in April 2020. The drug is currently in phase II for ARDS treatment and is ready to enter the phase III stage.

Drug: Lucinactant

Company: Windtree Therapeutics

Phase: Phase II

MoA: Cell membrane permeability enhancers

Special Designation: Fast Track Designation (US), Orphan Drug Product Designation (US, Europe)

Windtree’s Lucinactant (KL4 surfactant) is a synthetic surfactant that is physically comparable to human pulmonary surfactant and comprises a patented synthetic peptide KL4 (sinapultide), a 21-amino acid peptide designed to mimic the essential properties of human surfactant protein B. (SP-B). Windtree conducted a phase II trial in Covid-19 patients who were intubated and mechanically ventilated for related lung damage and ARDS to assess changes in physiological markers. The study aimed to determine the dosage regimen, tolerability, and functional changes in gas exchange and lung compliance following lucinactant administration. It has received Orphan Drug Product designation in the United States and Europe, as well as Fast Track designation in the United States, for the treatment of ARDS.

Drug: Solnatide

Company: Apeptico Forschung und Entwicklung GmbH

Phase: Phase II

MoA: Sodium channel agonists

Apeptico Forschung und Entwicklung GmbH is developing Solnatide (AP301; synonym for TNF-derived TIP-peptide), a synthetic compound based on the lectin-like domain of the Human Tumor Necrosis Factor. The AP301 peptide is water-soluble and may be inhaled orally into the lungs. APEPTICO has finished a phase II ARDS clinical trial. In Austria and Italy, the drug is approved under a compassionate use program for the treatment of COVID-19 patients with severe respiratory dysfunction and ARDS. In addition, the company secured a Grant Agreement with the European Commission for the expedited research and clinical use of solnatide in COVID-19 patients.

Future Perspectives in the ARDS Market

The ARDS market is expected to be dominated by high-priced agents such as stem cell therapies and other pipeline candidates with a better clinical profile. Several molecules are being evaluated and investigated by various pharmaceutical companies to strengthen the ARDS pipeline and raise the prospect of effective therapy shortly. The increased ARDS prevalence encourages drug research and development because it is likely to provide an appropriate environment for newer products to be profitable. Because no drug has been approved, demand for potential emerging therapies with a better clinical profile is expected to be high in the ARDS market in the future. Hence, due to all these factors, the ARDS treatment market is expected to witness an upsurge in the coming years. 

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