Novartis' Beovu safety woes could cost billions of dollars, says analyst

The launch of Novartis’ Beovu ophthalmology drug could be compromised after a safety warning from doctors over several cases of sight-threatening inflammation of blood vessels.

Beovu (brolucizumab) is a follow-up to the company’s blockbuster Lucentis (ranibizumab) and is approved for wet age-related macular degeneration (AMD).

It offers a less frequent dosing schedule, after an initial loading phase, and Novartis hopes it will appeal to doctors as this means cost per patient is lower compared with Lucentis and Bayer/Regeneron’s rival, Eylea (aflibercept).

But there are concerns that doctors will put off prescribing Beovu following a warning from the American Society of Retina Specialists (ASRS) issued over the weekend.

The ASRS noted that since approval on 7th October last year there have been 14 cases of vasculitis – inflammation of the blood vessels – with 11 reported to be occlusive retinal vasculitis, a sight-threatening condition.

Novartis' shares were down as much as 5.5% on Monday afternoon as the announcement spooked investors.

Analyst Peter Welford from Jefferies noted that so far around 46,000 Beovu injections have been administered in the US, and that a Novartis safety committee is reviewing the cases.

Jefferies had been forecasting peak global sales of $2.5 billion, but this could be halved because of a slower launch, hitting earnings per share by up to 2% or 2.5 Swiss francs ($2.56), according to Welford.

A “worst case scenario” where Beovu is withdrawn from the market cuts earnings per share by 4% and would add to Novartis’ woes following the phase 3 trial failure of fevipiprant for asthma.

A clinical trial of an intrathecal formulation of spinal muscular atrophy gene therapy Zolgensma has also been put on hold, leaving Novartis in need of “positive pipeline news”, said Welford.

In a note Welford said: “These safety concerns are likely to dampen retina physicians' initial uptake of Beovu, in our view, with many perhaps now waiting until their initial switched patients have received more injections of the drug before re-considering wider adoption.”

Jefferies’ own review of the FDA Adverse Event Reporting System database suggests a higher incidence of vasculitis, blindness and eye inflammation on Beovu since launch compared with either Eylea or Lucentis, although these reports have not undergone review.

The system recorded a spike in intraocular inflammation of Eylea in February 2018 but these concerns proved largely unfounded.

One potential cause is intraocular inflammation before administration – a contraindication on the drug’s label, and Welford added that a similar proportion of patients lost vision from baseline versus Eylea in trials so far.

There were five cases of retinal occlusive vasculitis after around 58,000 doses on trials, said Welford.