Anifrolumab approved by FDA for systemic lupus erythematosus

6th August 2021

The interferon antagonist anifrolumab has been cleared for the treatment of adults with moderate-to-severe systemic lupus erythematosus by the FDA.

Systemic lupus erythematosus (SLE) is a rare, chronic autoimmune disease which affects approximately six-times more women than men. It is the most common form of lupus, accounting for approximately 70% of all cases. There is a wide geographical variation in the incidence of SLE and has been found to vary between 23.2 cases per 100,000 in North America to 0.3 cases per 100,000 in Africa and the Ukraine. Other estimates suggest a general prevalence of approximately 1 to 10 per 100,000 person-years.

SLE is a systemic illness affecting many different organ systems including the skin, with a typical butterfly rash across the cheeks, the musculoskeletal system, producing arthritis and myositis, and constitutional symptoms such as fatigue, fever and weight loss. The cause of SLE remains unclear but the condition is characterised by the presence of autoantibodies and guidance from EULAR in 2019 has suggested treatment with hydroxychloroquine, glucocorticoids, immunosuppressants and biologics, in particular, belimumab. However, it has been shown that in patients with SLE, there is excessive production of type 1 interferon (IFN) and in particular, INF-alpha. Blockage of type 1 IFN could therefore represent a potential therapeutic modality for SLE.

Anifrolumab
Cell signalling in SLE occurs via activation of the IFN pathway mediated via the type 1 IFN receptor. Moreover, blockage of this IFN pathway may reverse immune dysregulation and the tissue damage seen in SLE. Anifrolumab binds to the IFN receptor and therefore potentially reduces some of the immune dysregulation seen in SLE.

The FDA based its approval of anifrolumab on the results of three separate trials. The first in 2016, undertaken in 305 patients, showed that treatment with intravenous anifrolumab (300mg or 1000mg) every 4 weeks for 48 weeks led to a substantial reduction in disease activity in patients with moderate-to-severe SLE. Further studies included TULIP-1 and TULIP-2, both of which were Phase III trials. The primary endpoint was the rate of British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), which is a validated global measure of treatment response among those with SLE. Interestingly, anifrolumab failed to reach the BICLA endpoint in TULIP-1 (37% vs 27%, anifrolumab vs placebo) when added to standard therapy. In contrast, significantly more patients assigned to anifrolumab than placebo, achieved the primary endpoint in TULIP-2, (47.8% vs 31.5%, anifrolumab vs placebo, p = 0.001).

An ongoing clinical trial in approximately 360 participants with moderate-to-severe SLE, is currently assessing the efficacy and safety of a subcutaneous form of anifrolumab in adults receiving standard therapy, over a 52-week period.

Anifrolumab is under regulatory review in both the EU and Japan.

Source. AstraZeneca August 2021

Inhaled interferon-beta shows promise as COVID-19 treatment

20th November 2020

Type 1 interferon (interferon-beta) is one of the first cytokines induced by a host’s innate immune system in response to infection by a virus in the lungs.

It is known that COVID-19 is able to suppress the release of interferon-beta in vitro and recent work has shown how there is a significant reduction in interferon activity in patients who develop a more severe infection. SNG001 is a recombinant interferon-beta in development for the treatment of virus-induced lower respiratory tract infections and has been formulated for inhalation via a nebuliser in an effort to achieve sufficient concentrations in the lungs. The drug has been shown to increase lung antiviral defences in patients with asthma and COPD and in this Phase II trial, a team from Southampton General Hospital, UK, decided to explore whether the drug had the potential to reduce the severity of respiratory symptoms in patients with COVID-19.

The researchers randomised patients, admitted to hospital because of COVID-19, to either interferon-beta or placebo which was given once daily for up to 14 days with a 28-day follow-up. The primary outcome for the study was a change in the clinical condition of patients as assessed by the WHO ordinal scale for clinical improvement (OSCI), which ranged from 0 (no evidence of infection) to 8 (death). A secondary outcome was the breathlessness cough and sputum scale (BCSS) as well as measures of the safety and tolerability of the drug.

Findings
A total of 101 patients with a mean age of 57.1 years (59% male) were randomised to SNG001 or placebo. Patients in the SGN001 group had more severe disease (OSCI >4) although those in the placebo group had more comorbidities. Patients receiving SNG001 had a two-fold higher odds of achieving a greater improvement on the OSCI scale (odds ratio, OR = 2.32, 95%CI 1.07-5.04, P = 0.033) on day 15 or 16 which increased to a three-fold on day 28 (OR = 3.15, 95% CI 1.39-7.14, p = 0.006). Only three patients died in the study, all from the placebo group. Furthermore, SNG001 reduced the odds of developing severe disease by 79%. The most frequent treatment-related side-effects were headache, 15% vs 10% (SNG001 vs placebo).

The authors concluded that their initial findings warrant a Phase III trial of the drug and suggest that SNG001 may also be of value against other seasonal respiratory viruses.

Reference
Monk PD et al. Safety and efficacy of inhaled nebulised interferon beta-1a (SNGOO1) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med 2020 https://doi.org/10.1016/ S2213-2600(20)30511-7