With input from Dr Monica Vasudev

1148: SNG001 recombinant interferon beta for inhaled delivery in COVID-19

Interferons represent a group of signaling proteins which are made and released by host cells in response to the presence of several viruses. A virus-infected cell releases interferons which causes the nearby cells to escalate their anti-viral defenses.

IFNs belong to the large class of proteins, termed cytokines, which are used for communication between cells to incite the protective defenses of the immune system that help eliminate the pathogens.

They are named for their potential to ‘interfere’ with viral replication by protecting the cells from viral infections. They also activate immune cells, like the natural killer cells and macrophages; enhance host defenses by up-regulating antigen presentation via increasing the expression of major histocompatibility complex (MHC) antigens. Some symptoms of infections, for instance, fever, muscle pain and flu-like symptoms, also occur as a result of the production of IFNs and other cytokines.

IFNs are divided among three classes: Type I IFN, Type II IFN, and Type III IFN.

Type I IFNs bind to a specific cell surface receptor complex - the IFN-α/β receptor. The type I interferons present in humans include IFN-α, IFN-β, IFN-ε, IFN-κ and IFN-ω. Type I interferons are generally produced when the body recognizes invasion by a virus. They are produced by fibroblasts and monocytes. However, type I IFN-α production is inhibited by the cytokine interleukin-10.

After release, type I interferons bind to specific receptors on target cells, resulting in the expression of proteins that will prevent the virus from producing and replicating its RNA and DNA.

IFN-α can be used to treat hepatitis B and C infections, while IFN-β can be used for the treatment of multiple sclerosis.

Interferon type II (IFN-γ in humans): This is also known as immune interferon and is activated by interleukin-12. Type II interferons are also released by cytotoxic T cells and type-1 T helper cells. However, they inhibit the proliferation of type-2 T helper cells. The previous leads to inhibition of Th2 immune response and induces Th1 immune response.

Expression of type I is induced in virtually all cell types when viral components are recognized, especially nucleic acids, by cytoplasmic and endosomal receptors. Type II interferon is induced by cytokines such as IL-12, and its expression is limited to immune cells such as T cells and NK cells.

[Source: Science Daily; https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/11%3A_Immunology/11.04%3A_Innate_Defenders/11.4B%3A_Interferons; https://www.iomcworld.org/medical-journals/interferon-47234.html; https://www.cebm.net/covid-19/drug-vignettes-interferons/; https://www.researchgate.net/publication/24232739_Interferons_and_viral_infections]

New Study

Hospitalized COVID-19 patients receiving SNG001, an inhaled nebulized interferon beta-1a, had higher odds of showing clinical improvement compared to those given placebo, reported a small pilot study in the U.K.. Patients receiving SNG001 for 14 days had greater odds of improvement on the WHO ordinal scale for clinical improvement on day 15 or 16 compared to those who received placebo, reported Tom Wilkinson, PhD, of University of Southampton in England, and colleagues. Patients in the intervention group had a higher likelihood of reverting to an OSCI score of 1, or no limitation of activities, on day 15 or 16, reported the authors in the Lancet Respiratory Medicine.

Interferon was found to fail in preliminary results from the WHOs SOLIDARITY trial. SOLIDARITY used subcutaneous interferon beta-1a. This trial; however, used nebulized therapy that delivers it directly to the respiratory tract.

Between March 30 and May 30, 48 patients were randomized to SNG001 and 50 were randomized to receive placebo in an intent-to-treat analysis. Patients had a mean age of 57 (59% male) and 80% were white. Baseline comorbidities included hypertension, cardiovascular disease, diabetes, chronic lung condition, and cancer.

SNG001 group had more severe disease, with 77% of patients receiving oxygen therapy compared to 58% in the placebo group. Mean duration of symptoms before treatment initiation was 10 days.

In the patients receiving SNG001, the likelihood of improvement was over three-fold greater on day 28 in comparison with placebo. Five patients underwent intubation or died, compared to three in the intervention group. Over 14 days treatment period, patients in the intervention group were over twice as likely to recover.

[Source: Medpage Today]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA