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Nov 16, 2015
 |  BioCentury  |  Product Development

On SLE's trail

What MedImmune is doing to increase odds of Phase III SLE success for anifrolumab

AstraZeneca plc's MedImmune LLC unit is following a clinical development trail for lupus candidate anifrolumab first blazed by Benlysta belimumab. The company hopes that its track record of successful mid-stage trials in the indication have set it up to confirm anifrolumab's Phase II higher response rates in an ongoing Phase III.

MedImmune presented Phase II results last week showing a placebo-adjusted response rate of 22.4% at 365 days for the dose now in Phase III, outperforming the 14% placebo-adjusted response rate on Benlysta's label and the 12.3% rates GlaxoSmithKline plc reported for a subcutaneous formulation of the drug.

Anifrolumab is a human mAb that targets Type I interferon receptor 1, inhibiting the activity of all Type I IFNs. Benlysta is a human mAb against B lymphocyte stimulator protein (BLyS; BAFF). Data for anifrolumab and subcutaneous belimumab were both presented at the American College of Rheumatology meeting in San Francisco (see "Lupus Comps," page 9).

But systemic lupus erythematosus (SLE) is a notoriously difficult indication to crack, and promising Phase II results have often failed to bear out in Phase III, in part because of tremendous heterogeneity and the unpredictable course of disease.

In SLE, autoantibodies and proinflammatory cytokines cause severe damage to any of a range of tissues, including the skin, kidneys, joints and tendons, eyes, blood vessels, heart, lungs and brain. Its clinical presentation varies widely from patient to patient, and even within a single patient over time, with a constellation of signs and symptoms that wax and wane.

In 2011, GSK's Benlysta became the first drug approved for SLE in more than 50 years. The drug's originator, Human Genome Sciences Inc., created a novel composite endpoint and designed a study that would improve the odds of demonstrating a drug effect after Benlysta failed a Phase II trial.

The endpoint was SLE Responder Index (SRI), which aims to ensure a drug is not improving some manifestations of lupus at the expense of others. SRI was defined as a four-point or greater improvement on the SELENA-SLEDAI scale compared to baseline, no worsening in lupus disease activity based on the physician global assessment (PGA) score, and an absence of any new organ involvement based on the British Isles Lupus Assessment Group (BILAG) organ domain score.

The trial was...

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