Novartis Responds to ASRS Note on Safety Concerns for Brolucizumab; Drug Receives EU Approval
Novartis is launching an internal and external review of new information that raises serious safety concerns over its wet age-related macular degeneration (AMD) drug brolucizumab-dbll (Beovu), the company confirmed to Eyewire News in February. Separately, the company announced that the drug had received marketing approval from regulators in the European Union (EU).
On February 23, the American Society of Retina Specialists (ASRS) shared a note with its membership stating that, since Beovu was approved by the US FDA in October 2019, ASRS has received reports of 14 cases of vasculitis associated with the drug, of which 11 were designated by the reporting provider as occlusive retinal vasculitis, a vision-threatening inflammatory eye condition.
In a statement sent to Eyewire News, Novartis said it is aware of recently reported adverse events following treatment with brolucizumab and is evaluating the cases.
“Novartis stands behind the safety and efficacy of [brolucizumab]. In addition to our own internal assessment, we have engaged an external safety review committee to further evaluate these post-marketing cases. We will continue to share details as they become available,” the Novartis statement said. “The FDA is aware of our ongoing review and we’re in the process of informing other health authorities. Our clinical development and pharmacovigilance teams are working with healthcare professionals to quickly obtain and evaluate all available information in order to classify these events and identify potential risk factors.”
An estimated 46,000 injections of brolucizumab have been administered in the United States as of February 21, 2020, according to Novartis.
The company noted that brolucizumab is contraindicated for patients with active intraocular inflammation, and that physicians should follow the guidance in the prescribing information that patients with active ocular inflammation should not be injected with brolucizumab. The product information for brolucizumab in the US lists a 4% rate of intraocular inflammation and a 1% rate of retinal artery occlusion as adverse events reported in the HAWK and HARRIER clinical trials of the drug.
In a separate development, Novartis in February received approval for brolucizumab from the European Medicines Agency, making it the first anti-VEGF agent approved in the EU to demonstrate superior resolution of retinal fluid (intraretinal fluid/subretinal fluid) compared with aflibercept (Eylea, Regeneron).
The EU approval was based on findings from the phase 3 HAWK and HARRIER clinical trials, in which brolucizumab met the primary endpoints, demonstrating gains in BCVA that were noninferior to aflibercept at year 1 (week 48). Vision gains at year 1 were maintained at year 2.
The approval is applicable in all 27 EU member states, as well as the United Kingdom, Iceland, Norway, and Liechtenstein.
RP Update: Phase 1/2a Trial for Stem Cell Therapy Will Expand; Gene Therapy for XLRP Showed Safety in Phase 1 Study
A study evaluating the safety and efficacy of a human retinal progenitor cell (hRPC) stem cell therapy candidate for retinitis pigmentosa (RP) will be expanded based on interim efficacy data in an ongoing phase 1/2a study, according to the therapy’s developer, the ReNeuron Group.
Three patients in the study successfully received treatment in one eye. Mean difference in VA improvement between treated eyes and untreated eyes was +7.3 letters at 12 months, the company stated in a February press release.
The company has submitted a protocol amendment to the FDA to expand the phase 1/2a study to treat up to a further nine patients in the phase 2a segment of the study at a dosage of 2 million hRPC cells; a dose of 1 million cells has been used in the study thus far.
In an unrelated study also in patients with RP, no significant safety concerns were observed after application of the gene therapy AAV8-RPGR (NightStar Therapeutics; now Biogen) for the treatment of X-linked RP (XLRP).1
In a 6-month, phase 1/2 dose-escalation clinical trial evaluating the safety of gene therapy for XLRP in 18 patients, some visual field improvements were observed.
XLRP is caused by a mutation on the gene RPGR, which blocks production of a protein necessary for photoreceptor cell function. RPGR mutations account for approximately 70% of all cases of XLRP.
1. Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, et al. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR [published online ahead of print February 24, 2020]. Nat Med.
Read Eyewire’s latest retina news at Eyewire.news/interests/retina.
Study of Light Therapy for Diabetic Retinopathy Will Expand
The Valeda System (LumiThera), a photobiomodulation platform being commercialized in Europe for the treatment of dry AMD, will also be investigated for use in treating diabetic retinopathy (DR), according to its maker.
LumiThera received the CE Mark to commercialize the Valeda System in the EU for the treatment of ocular diseases including dry AMD; the LIGHTSIDE II study is evaluating the safety and efficacy of the Valeda System for the treatment of dry AMD in the United States. Preclinical and clinical work has shown that the light therapy system also has potential benefits in treating diabetic edema, the company stated in a press release.
Market Scope: Retinal Surgical Device Market to Reach Nearly $2 Billion by 2025
The retinal surgical device market is expected to total more than $1.5 billion in 2020, with revenue rising to nearly $2 billion in 2025, according to the health care data firm Market Scope.
Market Scope estimated that 1.84 million vitrectomies will be performed globally in 2020.
The per-procedure revenue is typically 10 to 15 times greater than that for cataract surgery due to the numerous products required for a vitrectomy. Still, the number of vitrectomies is far lower than the 30 million cataract surgeries expected to be performed in 2020.
More than 55 companies compete in the global retinal surgical device market, but most specialize in only one or two product categories. Eight companies—Alcon, Bausch + Lomb, Dutch Ophthalmic Research Center (DORC), Geuder, Beaver-Visitec International (BVI), Nidek, Oertli, and Hoya—account for 82% of global revenue in this market.
Remembering Mina Chung, MD
Mina Chung, MD, died in February. She was 51.
Dr. Chung was an associate professor of ophthalmology at the University of Rochester Medical Center Flaum Eye Institute and a faculty member at the University of Rochester’s Center for Visual Science. She completed her fellowship in vitreoretinal surgery at the University of Iowa College of Medicine and residency at the USC University Hospital, where she was chief resident. She completed her undergraduate studies and medical degree at Yale.