|AstraZeneca Chief Medical Officer Briggs Morrison|
AstraZeneca had some upbeat news to report Wednesday morning, noting that a slate of key Phase III combination studies for the gout drug lesinurad crossed the finish line with positive results for three out of four primary endpoints, raising hopes that the once star-crossed pharma giant may be on the verge of a blockbuster approval. The late-stage misfire on one goal plus lingering safety issues leave some unanswered questions to consider. But the company says it plans to push ahead with regulatory applications with the late-stage data now in hand.
Back in February AstraZeneca ($AZN) turned in positive results for a Phase III of lesinurad as a solo treatment. But analysts were waiting to hear about the combo studies to get a better idea of the drug's market potential.
In two studies of lesinurad in combination with allopurinol (the aging generic Zyloprim), the combo hit its marks on statistical significance for both the 200 mg and 400 mg dose, with the standard therapy by itself falling short. In a separate study, lesinurad plus febuxostat hit the primary endpoint for the high dose but fell short of statistical significance for the 200 mg combo. Investigators highlighted some positive trends in that arm of the trial.
AstraZeneca is holding back specifics for a scientific conference, when it can detail results and help complete the picture on their new drug entry. A big gray area remains on the safety side of the equation. Regulators will want to fully scan the adverse renal events tracked in the 400 mg arm of the combo for febuxostat, an XO inhibitor. Adverse events involving the combo with allopurinol included upper respiratory tract infections, nasopharyngitis and back pain. In CRYSTAL, the three most commonly reported adverse events for patients receiving lesinurad in combination with febuxostat were nasopharyngitis, arthralgia and upper respiratory tract infection.
AstraZeneca expects to get a big share of the growing global market for gout with this drug. The therapy--acquired two years ago in the $1.26 billion buyout of San Diego-based Ardea--is a selective uric acid reabsorption inhibitor that blocks the URAT1 transporter, helping patients by reducing serum uric acid levels by normalizing acid excretion. Takeda and Ipsen ($IPN) won an approval for febuxostat 5 years ago, but their therapy doesn't help everyone.
"Gout is a serious, chronic and debilitating inflammatory disease. There is a significant unmet need, with 40 to 70 percent of gout patients not reaching target levels of serum uric acid with the current standard of care," said Briggs Morrison, AstraZeneca's chief medical officer. "We are encouraged by our initial review of the top-line results from the CLEAR1, CLEAR2 and CRYSTAL studies which provide important new information on the efficacy and safety of lesinurad in combination with febuxostat and allopurinol. These data indicate that combination therapy with lesinurad may be a potential treatment option for gout patients."
- here's the release