Horizon Therapeutics plc Initiates MIRROR Randomized Controlled Trial Evaluating KRYSTEXXA® (pegloticase injection) in Combination with Methotrexate to Increase Response Rates and Duration of Therapy

- Approach informed by regulatory guidance and real-world clinical experience -

DUBLIN, Ireland I June 20, 2019 I Horizon Therapeutics plc (Nasdaq: HZNP) today announced the initiation of a clinical trial evaluating KRYSTEXXA® (pegloticase injection) in combination with methotrexate as a strategy to increase the durability of response for patients living with chronic gout refractory to conventional therapies – also known as uncontrolled gout.

Treatment with biologic medicines can, in some patients, trigger the body’s immune system to develop anti-drug antibodies. These anti-drug antibodies can reduce the effectiveness of the biologic therapy. Immunomodulators, such as methotrexate, are often co-prescribed with biologics to help reduce this reaction. The Methotrexate to Increase Response Rates in Patients With Uncontrolled GOut Receiving KRYSTEXXA (MIRROR randomized controlled trial (RCT)), will evaluate the use of methotrexate as an immunomodulator to meaningfully reduce immune response to KRYSTEXXA in adult patients living with uncontrolled gout. The trial will assess whether the combination of KRYSTEXXA with methotrexate can enhance the demonstrated response rate of KRYSTEXXA, will confirm the safety and tolerability and provide information on the pharmacokinetics (PK) of the combined use. The primary endpoint will be the ability of KRYSTEXXA with methotrexate versus KRYSTEXXA alone to maintain a serum uric acid <6 mg/dL through Month 6. The MIRROR RCT follows the MIRROR open-label (OL) evaluation that was initiated last fall and is now fully enrolled (NCT03635957).

The trial initiation is informed by the positive results of an independent case series led by John K. Botson, M.D., R.Ph. C.C.D. and Jeff R. Peterson, M.D., presented at the 2018 American College of Rheumatology (ACR) meeting with updates presented at the 2019 European Congress of Rheumatology (EULAR), which demonstrated that the use of methotrexate with KRYSTEXXA was well tolerated and led to an improved overall response. In the series, all of the ten sequential patients sustained lower sUA levels over the course of the observation period (target <6 mg/dL) when receiving KRYSTEXXA combined with pre-treatment and co-administration of methotrexate, 15 mg orally once-weekly.1-2

“To address the systemic burden of uncontrolled gout on patients, we need to reduce serum uric acid levels rapidly and effectively,” said John K. Botson M.D., R.Ph., C.C.D., president, Alaska Rheumatology Alliance and rheumatologist, Orthopedic Physicians Alaska. “In our case series, we found that the use of methotrexate, which is a well understood and broadly utilized immunomodulator, may attenuate the immune response to KRYSTEXXA. We believe this combination may allow more patients on KRYSTEXXA to continue their treatment.”

In the trial, 135 adult patients will be randomized to receive methotrexate or placebo for four weeks and then receive treatment with KRYSTEXXA and methotrexate or KRYSTEXXA and placebo for 52 weeks, with the primary endpoint measured at Month 6, followed by a six-month follow-up period. The co-prescription of KRYSTEXXA and methotrexate is investigational and its safety and efficacy have not been established.

“We believe in continued evaluation of our therapies to achieve the best possible outcome for every patient,” said Paul Peloso, M.D., M.Sc., vice president and therapeutic area head, rheumatology, Horizon. “We’ve accelerated our plans for this trial based on the response seen in recent real-world case studies and the ongoing open-label evaluation, an approach aligned with our strategy to address the burden of disease from the lens of what’s most important to patients.”

About Uncontrolled Gout

Gout is a chronic, progressive inflammatory form of arthritis that is caused by excess uric acid in the body and needs to be managed aggressively.3 Over time uric acid can build up and form deposits, called tophi, inside the body and joints, which can have harmful effects including causing damage to the underlying bone.4 Patients with uncontrolled gout continue to have abnormally high levels of uric acid and continued symptoms of gout despite the use of conventional therapies. KRYSTEXXA is the only biologic approved by the U.S. Food and Drug Administration (FDA) for the treatment of uncontrolled gout in adult patients.

About KRYSTEXXA

INDICATIONS AND USAGE

KRYSTEXXA® (pegloticase injection) is a PEGylated uric acid specific enzyme indicated for the treatment of chronic gout in adult patients refractory to conventional therapy.

Gout refractory to conventional therapy occurs in patients who have failed to normalize serum uric acid and whose signs and symptoms are inadequately controlled with xanthine oxidase inhibitors at the maximum medically appropriate dose or for whom these drugs are contraindicated.

About Horizon

Horizon is focused on researching, developing and commercializing medicines that address critical needs for people impacted by rare and rheumatic diseases. Our pipeline is purposeful: we apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, please visit www.horizontherapeutics.com, follow us @HorizonNews on Twitter, like us on Facebook or explore career opportunities on LinkedIn.

References

  1. Pretreatment and co-administration with methotrexate improved durability of pegloticase response: a prospective, observational, proof-of-concept, case series. Poster presented at the 2018 Annual Scientific Meeting of the American College of Rheumatology (ACR), Chicago, IL, USA; October 19–24, 2018.
  2. Pretreatment and co-administration with methotrexate improved durability of pegloticase response: a prospective, observational, proof-of-concept, case series. Poster presented at the 2019 Annual European Congress of Rheumatology (EULAR), Barcelona, Spain; June 12-15, 2019.
  3. Keuhn, B. Chronic Disease Approaches Needed to Curb Gout’s Growing Burden. Journal of the American Medical Association. 2018;319(13):1308-1309.
  4. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011;63(10):3136-3141.

SOURCE: Horizon Pharma

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