Aiming to push Beovu into diabetic macular edema, Novartis hopes longer dosing interval can fix eye drug's safety woes

Beovu drug box
With new two-year data, Novartis hopes to stretch Beovu's dosing interval to up to 16 weeks for a potential approval in diabetic macular edema. (Novartis)

Expectations for Novartis’ Beovu crashed after the eye drug raised vision-threatening side effects in age-related macular degeneration (AMD) shortly after its launch. For a potential expansion into a new disease, the Swiss pharma hopes an increased dosing interval can solve that safety problem and offer patients added convenience.

In diabetic macular edema (DME), investigators recorded the same rates of retinal vasculitis and retinal vascular occlusion between Beovu and Regeneron and Bayer’s market-leading Eylea after two years of treatment in a phase 3 trial dubbed KITE, Novartis said Tuesday.

Beovu achieved that when most patients who successfully completed the loading phase and another 12-week treatment cycle remained on a 12- or 16-week dosing interval through the end of the two years, Novartis said.

Novartis' Beovu carried big expectations out of the gate in 2019, but, shortly after its approval in wet AMD, the American Society of Retina Specialists flagged safety concerns in a communication with doctors. The development derailed the med's launch in AMD, and, more recently, the FDA added warnings over retinal vasculitis and retinal vascular occlusion to the drug's label. 

In AMD, the recommended dose of Beovu is 6 mg monthly for the first three doses, followed by one injection every eight to 12 weeks. 

For the KITE study in DME, Novartis adopted an extended dosing regimen. In KITE, patients on Beovu got the drug every six weeks for five loading doses. Afterward, they could switch to receiving injections up to once every 16 weeks. 

RELATED: Novartis calls off 3 Beovu trials testing more frequent dosing on concerns of vision-threatening side effect

In the study, investigators tracked eye inflammation cases in 2.2% of Beovu takers, which was slightly higher than the 1.7% for Eylea. But neither treatment arm recorded any instances of retinal vasculitis, and the rates for retinal vascular occlusion were the same—0.6%—for both drugs.

Previously, Novartis said Beovu matched Eylea on the primary efficacy marker, the change in best-corrected visual acuity, at the one-year mark in the DME trial.

 The newer VEGF inhibitor also showed greater reductions over Eylea in central subfield thickness and in number of eyes with fluid, which is an indicator of disease activity. The efficacy results were consistent after two years, Novartis said.

“Patients with DME often struggle to adhere to burdensome treatment schedules as they manage various comorbidities related to diabetes,” Justus Garweg at Switzerland’s Lindenhof Hospital noted in a statement. Beovu’s extended dosing and fluid reduction suggest it could be used to manage DME, he added.

In another DME trial dubbed KESTREL, investigators recorded eye inflammation rates of 3.7% for 6-mg Beovu and 0.5% for Eylea after one year of treatment. Novartis expects to read out two-year data from KESTREL in the fourth quarter.

The company has filed data from both KESTREL and KITE to the FDA and the European Medicines Agency for potential approvals in DME.

RELATED: Novartis, stressing Beovu safety, matches Eylea in head-to-head diabetic macular edema trial

Still, the trial results likely won’t change doctors’ perceptions of Beovu. The drug, thanks to its better retinal fluid resolution, once carried blockbuster hopes as Novartis touted it as a proper follow-on to the Roche-partnered Lucentis. But the side effects have effectively driven doctors away for safer options.

In the first half of the year, Beovu only chalked up $86 million in global sales, down 18% at constant currencies. By comparison, Eylea’s sales jumped 25% year over year during the same period to $4.5 billion.

Meanwhile, Regeneron and Bayer are also pursuing Eylea dosing at intervals of 12 or 16 weeks. A phase 3 trial dubbed PHOTON is testing a high-dose Eylea in DME. Eylea’s FDA-recommended maintenance dose—and the one used in Novartis’ two trials—is 2 mg once every eight weeks. Though not as effective, the dosing interval could be extended to 12 weeks after one year of effective therapy, per FDA label.