AstraZeneca says that its experimental gout drug lesinurad failed to hit the primary biomarker target for the dose that it's now seeking regulatory approval for in the U.S. and Europe. And this latest Phase III--the last of a trio--continues to demonstrate that the pharma giant can't land evidence that the drug provides a clear benefit to patients in the time allotted for the study.
Physicians treat gout by going after lower serum uric acid (sUA) levels. And in that respect AstraZeneca ($AZN) says that it has abundant evidence of success. Testing a 200-mg and 400-mg dose, there has been data to support its argument that the drug works as billed. But the 400-mg dose is also linked to renal-related adverse events, which is why AstraZeneca is sticking with the 200-mg dose for its regulatory applications. And now it's detailing a failure on the key biomarker for the 200-mg patient group along with a lack of evidence that the drug can erase tophi, a manifestation of gout.
Investigators for the company reported that lesinurad, in combination with febuxostat, demonstrated greater sUA lowering to the target for tophaceous gout compared to febuxostat alone "at all months except at the time of the primary endpoint." The 56.6% vs. 46.8% scores did not represent a statistically significant outcome. There was a hit for a subgroup of subjects in the 200-mg arm. Lesinurad 400-mg in combination with febuxostat met the primary endpoint: 76.1% vs. 46.8%.
AstraZeneca has consistently argued that it has the data to support the use of the drug to reduce sUA levels to the recommended treatment targets for treatment-resistant patients. The company trumpeted top-line results last summer, then unveiled the results of the first two studies in the fall, holding back CRYSTAL data for last weekend's meeting of the European League Against Rheumatism Annual Congress.
"Lesinurad is very effective" at lowering sUA, says Chris Storgard, a vice president for clinical research and development at AstraZeneca. That's the underlying cause of gout, he adds, and there have been consistent signs in late-stage studies that the drug works as billed. It's true, he adds, that the drug hasn't registered a statistically significant benefit in reducing the number of flares or erasing tophi, but that will take more time than the studies were designed to run. Investigators will now continue to track benefits for patients in an extension study of the big Phase III program, but Storgard says it's uncertain just how long it might be before efficacy can be fully understood.
Success for lesinurad is important for AstraZeneca's management team, which has been scrambling to prove that the pharma giant can effectively push new products through late-stage development to an approval after years of frustrating setbacks and reorganizations. Bernstein's Tim Anderson has projected potential 2020 sales for this drug at $582 million, making it a valuable contender in AstraZeneca's pipeline.
- here's the release