Benzinga | Jun 2, 2021 08:17AM EDT

Horizon Therapeutics Says Presents New Data On Robust Pipeline At EULAR European Congress Of Rheumatology

Horizon Therapeutics plc (NASDAQ:HZNP) today presented new data during the EULAR European Congress of Rheumatology from the ongoing PROTECT study, which provides further insight into utility of KRYSTEXXA (pegloticase injection) as a treatment for people with uncontrolled gout (chronic gout refractory to conventional therapies) who have undergone a kidney transplant.

The Prospective Study of Pegloticase in Transplant patients (PROTECT) trial is an ongoing Phase 4, multi-site, open-label trial evaluating the safety and efficacy of KRYSTEXXA in adults with uncontrolled gout who have received a kidney transplant and are on stable immunosuppressive therapy. Participants are receiving KRYSTEXXA (8 mg once every two weeks for 24 weeks) to determine response rate (defined as serum uric acid (sUA) <6 mg/dL for at least 80 percent of the time) during Month 6.1

At time of data cut, estimated glomerular filtration rate (eGFR), a key indicator of kidney function, remained stable for all patients throughout KRYSTEXXA treatment. In the 10 patients with Week 24 eGFR measurements, the mean eGFR was 41.6 ? 10.6 mL/min/1.73 m2 (median of 41.0) at baseline and 43.8 ? 11.9 mL/min/1.73 m2 (median of 46.6) at Week 24, with a mean improvement of 2.3 ? 8.1 mL/min/1.73 m2 during the treatment. Further, through health assessment questionnaires, patients reported clinically meaningful reductions in pain (average reduction of 26.7 +/- 30.3 from baseline of 35.9 +/- 30.2 on a scale of 0-100) and disability (average reduction of 0.2 +/- 0.5 from baseline of 1.0 +/- 1.0 on a scale of 0-3).

"Given kidney transplant patients have a 10-fold or higher prevalence of gout compared to non-transplant patients, it is particularly important to effectively manage this disease," said Abdul Abdellatif, M.D. F.A.S.N. primary investigator and adjunct assistant professor, Baylor College of Medicine Nephrology Division, and Kidney Hypertension Transplant Clinic of Clearlake Specialties. "Expanding datasets from the PROTECT trial indicated that KRYSTEXXA could represent a durable and tolerable therapy for this sensitive patient population."

The PROTECT trial was fully enrolled in January 2021 with 20 patients who received a kidney transplant and as such were on two to three immunosuppressive agents each. At the time of data analysis, 10 patients had completed the full course of therapy and five were receiving ongoing treatment; three patients discontinued the study (one withdrew consent, two withdrew due to COVID-19 concerns) and two discontinued treatment due to meeting sUA monitoring protocols. In the trial, 15 patients experienced an adverse event, with the majority (12 of 15 patients) reporting mild-to-moderate events, none of which led to discontinuation of therapy. No anaphylaxis or infusion reaction events were reported. The trial is expected to be completed in Fall 2021. Preliminary findings of the PROTECT clinical trial: pegloticase efficacy and safety in kidney transplant recipients (Abstract: POS1122)

"The persistent challenge of a chronic disease like gout requires that we understand how the experience varies among patient populations, especially more vulnerable populations like kidney transplant recipients, and design regimens accordingly to meet treatment goals," said Jeffrey D. Kent, M.D., FACG, FACP, executive vice president, medical affairs and outcomes research, Horizon. "The data we continue to collect through robust research programs on KRYSTEXXA provides not only clarity on the role of this important therapy, but also confidence to physicians that this can support holistic patient care."

Additional KRYSTEXXA Presentations

Other KRYSTEXXA presentations during EULAR include posters highlighting the pharmacokinetic and anti-drug antibody profile when KRYSTEXXA is co-administered with methotrexate as part of the MIRROR open-label trial (Pharmacokinetics of Pegloticase and Methotrexate Polyglutamate(s) in Patients with Uncontrolled Gout Receiving Pegloticase and Co-treatment of Methotrexate [Abstract POS1136]), as well as real world insights on the demographics, comorbidities and renal functions of people who received KRYSTEXXA (Demographics, Comorbidities, and Renal Function of Uncontrolled Gout Patients Who Received Pegloticase: Finding From A Large US Claims Database [Abstract POS1121]). Notably, data from the U.S. claims database found that 83 percent (40 of 48) of people who had a full course of treatment captured experienced stable or improved chronic kidney disease. For people with advanced chronic kidney disease (Stages 3- 5), data showed that 89 percent (16 of 18 people) experienced stable or improved chronic kidney disease.

Oral Presentation on HZN-4920

Additionally, during an oral session on June 3, 2021 at 10:15 a.m. CEST, the company will present data assessing the duration of clinical improvement beyond Day 169 of its original 2019 trial of people with moderate-to-severe rheumatoid arthritis (RA). This observational follow-up study of 16 out of 24 patients, who had received 1000 mg or 1500 mg HZN-4920 at one of two sites in Poland, showed that HZN-4920 added to stable DMARD therapy may provide a prolonged, clinically meaningful benefit to patients with moderate to severe RA. Duration of clinically meaningful benefit was assessed by need for rescue therapy. Interpretation of these data is limited. The duration of clinical response needs to be confirmed in prospective, double-blind, placebo-controlled studies. (Duration of Clinical Efficacy Following Treatment with VIB4920 in Subjects with Moderate to Severe Rheumatoid Arthritis (Abstract: OP0120)

About HZN4920

This investigational compound is a fusion protein binding CD40L on T cells, blocking their interaction with CD40-expressing B cells. Horizon is currently conducting Phase 2 clinical trials with HZN4920 in Sj?gren's syndrome, rheumatoid arthritis and kidney transplant rejection.