NRx Pharmaceuticals Partners with MannKind Corporation to Develop ZYESAMI (aviptadil) Inhaler for Respiratory Conditions

On Aug 4, 2021

NRx Pharmaceuticals (NRx) announced it has signed an agreement with MannKind Corporation to develop a dry powder formulation of ZYESAMI (aviptadil), a synthetic form of human Vasoactive Intestinal Peptide (VIP), produced by the body to help protect cells against inflammatory conditions. Development will be based on MannKind’s proven Technosphere platform, that is the basis of the US Food and Drug Administration (FDA) -approved Afrezza inhaled insulin product.

Concept image of dry powder inhaler as currently approved for use with Afrezza® inhaled insulin

In June 2020, FDA awarded a Fast Track Designation to NRx for the use of aviptadil for the treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome associated with COVID-19. The investigational drug has demonstrated a greater than 2-fold increased odds of survival at 60 days in a phase 2b/3 clinical trial, and demonstrated significantly reduced IL-6 cytokine formation (commonly known as cytokine storm) compared to placebo. Both intravenous and inhaled formulations of ZYESAMI are in phase 3 clinical trials funded by the US National Institutes of Health, the Biomedical Advanced Research Development Authority (BARDA), and by NRx.

Although Vasoactive Intestinal Peptide (VIP) was discovered in 1970, NRx was the first to formulate aviptadil (the synthetic form of VIP) for human intravenous and inhaled use under the “Good Manufacturing Practices” (GMP) standards required by FDA and other regulators in 2020. The stable, sterile liquid formulation of ZYESAMI developed by NRx is suitable for emergency use and stockpiling purposes. With clinical effects of aviptadil now emerging in clinical trials, NRx is broadening its focus to develop a simple, room-temperature inhaled delivery system that is convenient for patients and is already proven in commercial manufacture. Senior FDA officials and others have emphasized the need to develop inhaled drugs to treat COVID and other acute lung disorders in order to increase patient convenience and move treatment from the ICU to the outpatient setting.

“As we continue to identify the beneficial effects of VIP in treating various respiratory disorders, development of a convenient dosing method that offers multi-year stability at room temperature is key to meeting the needs of patients.” said Prof Jonathan Javitt, MD, MPH, CEO and Chairman of NRx (see concept image). “I had the privilege of working closely with Dr. Alfred Mann, on the refinement and regulatory approval of MannKind’s Technosphere platform and have long admired its simplicity and elegance. On many occasions he and I discussed his vision to extend Technosphere beyond insulin to solve the unique stability and administration challenges of peptide-based drugs. I am personally delighted to be partnering once again with MannKind and bringing Dr. Mann’s vision to life.”

“We are looking forward to the collaboration with NRx and looking for an avenue to marry the benefits of our Technosphere technology with ZYESAMI,” said Michael Castagna, PharmD, Chief Executive Officer of MannKind Corporation. “Our focus is to continue to explore ways that our Technosphere technology can deliver unique compounds in a targeted and convenient manner for patients with serious lung diseases.”