- AstraZeneca's lupus drug anifrolumab reduced disease activity in nearly half of patients in the TULIP-2 trial, significantly more than the 32% of patients on placebo who saw improvement. The results of the trial were published Wednesday in the New England Journal of Medicine.
- Anifrolumab failed to show a significant benefit in an earlier trial using a different clinical measurement, raising questions over whether the Food and Drug Administration would approve the drug without a second positive pivotal trial.
- If approved, anifrolumab would compete against GlaxoSmithKline's Benlysta, which had sales of 473 million pounds, or around $617 million, in 2018. GSK yesterday announced results from a Benlysta trial in patients with a kidney complication called lupus nephritis.
TULIP-2, AstraZeneca's study, used a scale called BICLA, which measures improvement based on disease activity, organ health, physician assessment and several other components.
This differs from the measurement in TULIP-1, which used something called the SLE Responder Index 4. GSK used the SRI in two of the three clinical trials it ran to win approval of Benlysta (belimumab).
Using SRI, Benlysta produced an improved response of a similar magnitude as anifrolumab — a 9 percentage point improvement in patient response over placebo in one trial and 14 percentage points in another.
However, in TULIP-1, the AstraZeneca trial using this scale, anifrolumab generated a response in 36% of patients, compared with 40% of patients taking placebo. Benlysta stimulated a response in 43% and 58% of patients when measured by the SRI.
Lupus is a complex autoimmune disorder that affects patients differently, requiring complicated measurement of improvement. This can lead to mixed trial results, as happened when GSK was seeking approval for Benlysta and a Phase 3 trial using yet another set of measurements failed to show the drug's efficacy.
In an editorial accompanying the NEJM article on TULIP-2, Jane Salmon of Weill Cornell Medical School and Timothy Niewold of New York University Medical School write that BICLA and the SRI weight patient response differently, which can account for the different trial outcomes.
BICLA measures partial responses while SLE counts only complete responses, for example, and only SLE measures blood biomarkers, they write. In addition, SRI puts more weight on arthritis than rash, according to the two rheumatologists.
Benlysta was the first drug for lupus since 1955 when GSK launched it in 2011, so the FDA is keenly aware of the need for more treatment options. However, it will need to balance the demand for more drugs against the mixed clinical results in making its decision to clear the way for AstraZeneca to submit anifrolumab for review.