More than a decade after Krystexxa's original approval, Horizon Therapeutics is breathing new life into the med by winning an expanded FDA label to improve treatment outcomes for patients with uncontrolled gout.
The label expansion, announced Friday, combines Krystexxa with the chemotherapy and immunosuppressive drug methotrexate. In a randomized trial dubbed Mirror, Horizon demonstrated that patients on the combo responded more favorably compared with those who received a combination of Krystexxa and placebo.
Specifically, 71% of patients in the Krystexxa-methotrexate arm met the threshold of serum uric acid reduction for the primary endpoint. That compared with 39% of those who received Krystexxa and placebo.
The Horizon drug won its original FDA approval in 2010 to treat chronic gout that is unmanageable with conventional therapies, a condition known as uncontrolled gout. It’s the first and only biologic approved for the disease. However, some patients treated with Krystexxa develop anti-drug antibodies over time, limiting the effectiveness of the drug. That’s where methotrexate comes in.
Uncontrolled gout can lead to arthritis in multiple joints due to too much serum acid, causing severe pain, Theresa Podrebarac, senior vice president of clinical development at Horizon, said in an interview with Fierce Pharma. While methotrexate isn’t typically used to treat gout, it can be used to treat arthritis conditions.
Years ago, pilot data suggested that treatment with the chemo drug could prevent the formulation of anti-drug antibodies, Podrebarac said. Upon testing the combination, researchers saw tophus, a collection of uric acid that can lead to debilitating symptoms due to gout in the joints, “melt away," she added.
Horizon considers this a “very important finding” about how to better use the product, Podrebarac said.
On the safety side, patients who received the combination had fewer infusion reactions, she noted.
Gout is an important treatment area for the rare disease-focused company. Over the years, Horizon has embarked on several collaborations to determine how to reach the high unmet patient needs, including one with HemoShear Therapeutics to discover and develop novel therapies for the disease.
Last year, Horizon unveiled a collaboration with Arrowhead Pharmaceuticals to develop an RNAi therapeutic for the disease.
With Krystexxa, Horizon is “constantly still looking” for how to improve the patient experience, such as spreading out infusion times to once a month as opposed to once every two weeks, Podrebarac said.
When Horizon first acquired the drug in its $510 million purchase of Crealta in late 2015, the company started refocusing Krystexxa toward patients with more severe and treatment-resistant gout. The med has been a strong performer in the years since, prompting Horizon to expand its sales force in 2017.
Last year, the drug raked in record net sales of $565.5 million, representing year-over-year growth of 39%. It’s forecasted to grow more than 20% in 2022.