FSD Pharma announced the U.S. Food and Drug Administration (FDA) has given the company permission to submit an Investigational New Drug Application (IND) for the use of FSD-201 (ultramicronized palmitoylethanolamide, or ultramicronized PEA) to treat COVID-19, the disease caused by the SARS-CoV-2 virus. Severe COVID-19 is characterized by an over-exuberant inflammatory response that may lead to a cytokine storm and ultimately death. FSD Pharma is focused on developing FSD-201 for its anti-inflammatory properties to avoid the cytokine storm associated with acute lung injury in hospitalized COVID-19 patients.
“FDA’s permission to design a proof-of-concept study in COVID-19 patients evaluating clinical doses of FSD-201 is a paradigm shift for FSD Pharma and is the result of outstanding work conducted by Dr. Edward Brennan, President FSD BioSciences, and his team,” said Raza Bokhari, MD, Executive Co-Chairman & CEO. “We contacted the FDA in late-March 2020 after becoming aware that several Italian physicians and scientists were advocating for use of ultramicronized PEA for patients suffering from symptoms of COVID-19, based on the drug’s mechanism of action as a potent and safe anti-inflammatory agent that reduces the production of pro-inflammatory cytokines. Numerous studies over the past 40 years also validate the efficacy and safety of ultramicronized PEA in the treatment and prophylactic effects in respiratory infections. These studies also pointed out that the ease of application of PEA offers the possibility to have a quick therapeutic answer ready in case of a flu epidemic.”
Based on the FDA feedback received to date, we expect the trial will be a randomized, controlled, double-blind, U.S. multicenter study to assess the efficacy and safety of FSD-201 dosed 600mg or 1200mg twice-daily plus standard of care (SOC) versus SOC alone in symptomatic patients with clinical presentation compatible with COVID-19. Eligible patients will present with symptoms consistent with influenza/coronavirus signs (fever, dry cough, malaise, difficulty breathing) and/or newly documented positive COVID-19 disease.
The primary endpoint is to determine if FSD-201 plus SOC provides a significant improvement in clinical status (i.e., shorter time to symptom relief). Key secondary objectives include determining if FSD-201 plus SOC demonstrates additional benefit in terms of safety, objective assessments such as length of time to normalization of fever, length of time to improvement of oxygen saturation and length of time to clinical progression including time to mechanical ventilation or hospitalization, and length of hospital stay. The exploratory endpoint is cytokine clearance as measured by Enzyme Linked Immunosorbent Assay (ELISA).
The treatment period is expected to be 14 days. All patients who experience clinical benefit are expected to continue to receive their assigned treatment until study completion.
More than 600 scientific papers attest to the physiological properties of PEA and its role as an endogenous modulator, as well as its pharmacological and therapeutic effects, specifically its anti-inflammatory profile.
PEA acts via multiple mechanisms either directly to activate PPAR-α and GPR55 or indirectly through the inhibition of FAAH, which increases endogenous levels of anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG). These endocannabinoids directly activate CB2 (or CB1) receptors and TRPV1 channels (entourage effect). PEA may also activate TRPV1 channels via PPAR-α.
AEA has been shown to inhibit tumor necrosis factor-α-induced NF-kappa B activation, independent of CB1 and CB2. Saturated acylethanolamides such as PEA (an endogenous congener of AEA) may act in an analogous fashion to modify chronic inflammation in autoimmune disorders.
Nobel laureate Rita Levi-Montalcini described the importance of the activation of the inflammatory cascade and in 1993 discovered that PEA functions as a mast cell modulator by reducing mast cell migration and degranulation; thus, PEA reduces the pathological overactivation of these cells and the activity of proinflammatory cytokines (such as TNF-α and IL6), cyclooxygenase and iNOS. It is this excess immune response activity that contributes to the physiologic derangement induced by influenza viruses and sets up the pathogenesis of the “cytokine storm.”
In summary, PEA down regulates hyperactive mast cells, inhibits iN...
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