AZ's lupus drug fails in late-stage trial

AstraZeneca has been dealt a setback in attempts to rebuild its pipeline after anifrolumab lupus drug failed to reduce disease activity in a phase 3 trial.

There was no word on whether AZ will continue with development after the disappointment in the TULIP 1 trial, which the company hoped would be included in regulatory filings.

But AZ, which is developing a new generation of drugs after several blockbusters went off-patent, said it will conduct a “full evaluation” of anifrolumab when data from the TULIP 2 trial become available later this year in patients taking only a higher dose of the drug.

TULIP 1 failed to meet its endpoint of a statistically significant reduction in disease activity in patients with systemic lupus erythematosus (SLE), measured by an index of symptoms at 12 months.

The trial was a randomised, double-blinded, 52-week placebo-controlled multi-centre trial assessing safety and efficacy of anifrolumab in patients with moderate-to-severe SLE.

TULIP 1 randomised 460 eligible patients to receive a fixed-dose intravenous infusion of 150mg anifrolumab, 300mg anifrolumab, or placebo every 4 weeks.

Meanwhile, TULIP 2 randomised 373 eligible patients to receive a fixed-dose intravenous infusion of 300mg anifrolumab or placebo every 4 weeks.

AstraZeneca hopes anifrolumab could be a new therapy for a disease where GlaxoSmithKline’s Benlysta (belimumab) has carved itself a niche.

Approved by the FDA in 2011, Benlysta was the first medicine for the disease in more than half a century, with sales of around £114 million in the last quarter. GSK's drug was also last year approved in a self-injectable subcutaneous formulation.

But Anifrolumab works in a different way and is not an add-on therapy to standard care like GSK’s drug.

Formerly known as MEDI-546, anifrolumab was developed by AZ’s MedImmune biologics unit, and is a fully human monoclonal antibody that binds to subunit of the type 1 interferon receptor.

This blocks the activity of all type 1 interferons, which are involved in the inflammatory pathways.

Around 60%-80% of adults with lupus have an increased type 1 interferon gene signature, which has been shown to correlate with disease activity.

AZ’s chief medical officer Sean Bohen said: “SLE is a debilitating autoimmune disease with significant unmet need among patients who struggle to achieve meaningful disease control. The result of this trial is disappointing for patients and the lupus community.”

SLE is an autoimmune disease in which the immune system attacks healthy tissue in the body instead of primarily targeting viruses or other foreign invaders. Lupus can cause a range of symptoms, including pain, rashes, fatigue, swelling in joints and fevers. It is associated with a greater risk of death from causes such as infection and cardiovascular disease.