Interferons in COVID-19: missed opportunities to prove efficacy in clinical phase III trials?

Interferons were repeatedly used in the therapy of COVID-19 due to their antiviral effects. Three recently published randomized controlled clinical phase III trials (WHO SOLIDARITY, ACTT-3, and SPRINTER) missed their primary objectives, i.e.

Interferons in the Therapy of Severe Coronavirus Infections: A Critical Analysis and Recollection of a Forgotten Therapeutic Regimen with Interferon Beta.

The pharmacological and immunological properties of interferons, especially those of interferon beta, and the corresponding treatment strategies are described, and the results of studies with different interferons in coronavirus infections are analysed. Furthermore, the data obtained with high-dosed native interferon beta in life-threatening acute viral diseases as well as the results of clinical pilot studies with high-dosed recombinant interferon beta-1a are provided because they serve as the rationale for the proposed therapeutic regimen to be applied in acute viral infections. This regimen differs from those approved for treatment of multiple sclerosis and consists of interferon beta-1a administered as a 24 hour intravenous infusion at a daily dose of up to 90 µg for 3-5 consecutive days.

Long-term survival benefit after adjuvant treatment of cutaneous melanoma with dacarbazine and low dose natural interferon alpha: A controlled, randomised multicentre trial.

In a prospective, controlled, randomised, multicentre study 252 patients with totally resected cutaneous melanoma (248 in stage II-III and 4 in stage IV) were either treated with two doses of dacarbazine (DTIC) followed by a 6-month treatment with 3 MU thrice weekly of highly purified natural interferon-alpha (n = 128; arm A) or received no adjuvant treatment (n = 124; arm B). Treatment was well tolerated. After a median follow-up of 8.

Successful application of highly purified natural interferon alpha (multiferon) in a chronic hepatitis C patient resistant to preceding treatment approaches.

A currently 65-year-old patient with histologically proven chronic hepatitis C and chronic hepatitis B (seroconversion in 1990) and additional compensated cirrhosis of the liver (Child A) achieved sustained complete biochemical and viral response following 5 and 14 months respectively of therapy with highly purified natural leukocyte interferon-alpha (3 x 3 MU weekly, nIFN-alpha, Multiferon). Prior to this treatment, various other therapy approaches including recombinant interferon-alpha2b (rIFN-alpha2b) or a combination of natural interferon-beta (nIFN-beta) and interferon-gamma (rIFN-gamma) had been carried out. Unfortunately, these had been unsuccessful.

Successful long-term application of highly purified natural interferon-alpha (multiferon) after preceding interferon approaches in a chronic hepatitis C patient with thrombocytopenia.

Treatment approaches with recombinant IFN-alpha2b and natural IFN-beta in a patient with chronic hepatitis C (genotype 1b) and cirrhosis had, in both cases, to be terminated prematurely due to breakthrough phenomena and thrombo-leukocytopenia up to WHO grade 3. After the patient was switched to highly purified natural IFN-alpha (Multiferon) the thrombocyte and leukocyte counts increased significantly, and sustained complete biochemical and virological response could be achieved.