Novartis: Positive DME data for brolucizumab in KITE trial

Novartis announced positive topline results from the phase 3 KITE study of brolucizumab 6 mg (Beovu) versus aflibercept for patients with diabetic macular edema (DME).

“Living with DME has significant impact on patients’ lives and frequent treatment injections are needed to control the increased fluid in the eye,” said Dirk Sauer, who leads Novartis Pharma Ophthalmology’s drug development efforts, in a prepared statement. “This data confirms our strong belief in [brolucizumab] as a potential therapy for DME patients, and if approved, will provide patients with a new treatment option to control their disease through better resolution of retinal fluid and central subfield thickness (CST) reductions.”

According to the drugmaker, the trial met its primary and key secondary endpoints, demonstrating non-inferiority for brolucizumab versus aflibercept 2 mg in mean change in best-corrected visual acuity at year 1 (week 52).

In a secondary endpoint, Novartis reported that brolucizumab demonstrated superior improvement compared with aflibercept in change of CST over the period of week 40 through week 52.

According to the statement, more than half of patients in the brolucizumab arm were maintained on a 3-month dosing interval through year 1, following the loading phase. All aflibercept patients were on a 2-month dosing interval after the loading phase.

In the KITE study, brolucizumab demonstrated an overall well-tolerated safety profile comparable to aflibercept. In addition, the rate of intraocular inflammation was equivalent between brolucizumab and aflibercept. The KITE trial is an ongoing 2-year study with 360 patients with DME across 80 centers in 23 countries.

Novartis is actively progressing studies across wet age-related macular degeneration (AMD), DME, retinal vein occlusion and proliferative diabetic retinopathy. The favorable benefit-risk of the brolucizumab development program was supported by a company-requested review of ongoing studies by the FDA. In its KESTREL study, Novartis is evaluating brolucizumab in the DME indication and anticipates results later this year, when the drugmaker will assess next steps with health authorities.

Brolucizumab was granted a Permanent J-code that began Jan. 1, 2020. The FDA gave its approval of brolucizumab for the treatment of patients with wet age-related macular degeneration (AMD) in the last quarter of 2019.

In addition, the European Medicines Agency (EMA) has approved a safety label update for brolucizumab, according to the company. The update to the EU label includes the addition of retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation under “Special warnings and precautions for use” (section 4.4) and “Undesirable effect” (section 4.8). The label notes that patients developing these events should discontinue treatment and the events should be promptly managed.

“This label update is one of the many efforts Novartis is taking to help physicians make informed decisions,” said Marcia Kayath, global head of medical affairs and chief medical officer, Novartis Pharmaceuticals. “Novartis is committed to fully understanding and transparently communicating the safety profile of [brolucizumab]. To this purpose, we have established a coalition, which is a fully dedicated internal team collaborating with top global experts to examine the root cause, risk factors, mitigation and potential treatment recommendations.”

The label update is applicable to all 27 European Union member states as well as the UK, Iceland, Norway and Liechtenstein. The drug is now approved for the treatment of wet AMD in more than 40 countries, including in the US, EU, UK, Japan, Canada, and Australia, according to the company.

REFERENCE

1. ClinicalTrials.gov. Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema (KESTREL). https://clinicaltrials.gov/ct2/show/NCT03481634. Accessed September 2020.