First inhaled interferon COVID-19 readout bolsters case for class, but more robust data needed

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Data suggesting an inhaled IFNB1 product from Synairgen can reduce the chance a patient with COVID-19 develops severe disease gave a jolt to the biotech’s shares Monday, but more statistically robust data are still needed to demonstrate if and when the cytokine provides a benefit over standard of care or other antivirals.

Synairgen plc (LSE:SNG) added 153.50p (421%) to 190p Monday after reporting Phase II data for several secondary endpoints. The company did not disclose safety data or results for the primary endpoint, defined as clinical improvement on an eight-point scale, according to ClinicalTrials.gov. The dosing schedule was also undisclosed.

The double-blind, placebo-controlled trial enrolled 101 patients hospitalized with COVID-19. SNG001, an inhaled formulation of IFNB1, reduced the odds of developing severe disease by 79% compared with placebo, though with a wide 95% confidence interval (odds ratio=0.21; 95% CI: 0.04, 0.97; p=0.046). Severe disease was defined as requiring ventilation or resulting in death during the 16 day treatment period.

Patients who received SNG001 were more than twice as likely as those who received placebo to recover by the end of the treatment period, defined as no limitation of activities or no clinical or virological evidence of infection (HR=2.19, 95% CI: 1.03, 4.69; p=0.043).

Three patients (6%) in the placebo group died; there were no deaths in the SNG001 treatment arm.

SNG001 did not significantly increase the likelihood of hospital discharge. The therapy had a median time to discharge of six days compared with nine days for placebo (HR=1.72, 95% CI: 0.91, 3.25; p=0.096).

IFNB1 for COVID-19
Synairgen co-founder and University of Southampton professor Stephen Holgate said in a statement that SNG001, which was originally developed to treat chronic obstructive pulmonary disease, “restores the lung’s ability to neutralise the virus.”

Coronaviruses can suppress endogenous IFNB1 production to evade the innate immune system. By directly delivering the cytokine to the lungs, Synairgen aims to prevent or reduce cell damage and viral replication.

The targeted effect and ease of administering SNG001 -- the only inhaled IFNB1 in the clinic for COVID-19 -- could offer advantages over injected or infused products.

Two master protocol trials are evaluating IFNB1: the WHO’s SOLIDARITY trial is testing IFNB1 in combination with the generic HIV antiviral lopinavir-ritonavir, and the U.K.’s REMAP-CAP is evaluating drug cocktails that include IFNB1 (see “REMAP-CAP has Lesson for Studying Drug Cocktails”).

According to BioCentury’s COVID-19 Resource Center, two other biopharmas are testing IFNB1 products in the clinic for the disease: Merck KGaA (Xetra:MRK) has its subcutaneous multiple sclerosis (MS) drug Rebif; and Faron Pharmaceuticals Oy (LSE:FARN; HSE:FARON) has Traumakine, an intravenous formulation in Phase III testing for acute respiratory distress syndrome (ARDS).

A third group, the Tehran University of Medical Sciences in Iran, is studying subcutaneous MS drug ReciGen from CinnaGen Pharmaceutical Group. In May, the team published a preprint in medRxiv showing that ReciGen decreased mortality and -- unlike SNG001 -- increased the rate of discharge.

Of 42 patients with severe COVID-19 who received ReciGen, 66.7% were discharged by day 14, compared with 43.6% of the 39 patients given placebo (odds ratio=2.5, 95% CI: 1.05, 6.37).

Patients received ReciGen injections three times per week for two weeks.

Additionally, the Tehran team found that the IFNB1 arm had a 28-day mortality rate of 19%, compared with 43.6% for placebo (p=0.015).

ReciGen did miss the primary endpoint of time to clinical response, as measured by a two point change on a six-point scale that ranges from death to discharge (HR=1.10, 95% CI: 0.64, 1.87, p=0.72). The therapy also missed several secondary endpoints, such as duration of hospital stay, length of ICU stay and duration of mechanical ventilation.

Targets

IFNB1 - Interferon-β

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