Abstract
In this review period, a nonpreserved formulation of a topical ocular hypotensive agent received U.S. Food and Drug Administration (FDA) approval. Several New Drug Applications (NDAs) were submitted to the FDA for treatment of dry eye disease, anterior segment pupil function, geographic atrophy (GA), and glaucoma. Public policy continues to change on accelerated drug approvals, drug pricing, generic drug utilization, and off-label use of products.
Ophthalmic Pharmaceuticals and Biologics
Aldeyra submitted an NDA to the U.S. FDA for topical ocular reproxalap for the treatment of signs and symptoms of dry eye disease (November 2022). The company also submitted an NDA for ADX-2191 (methotrexate) for the treatment of primary vitreoretinal lymphoma (December 2022).
BRIM Biotechnology received an orphan designation from the FDA for its BRM424 peptide for the treatment of neurotrophic keratitis (December 2022).
Cognition Therapeutics is planning a phase 2 trial of its CT1812, an oral sigma-2 (σ-2) receptor modulator in GA (December 2022).
Eyenovia stated that the FDA has accepted for review its NDA for MydCombi™ ophthalmic spray (a combination of tropicamide and phenylephrine) for in-office diagnostic mydriasis (December 2022).
Iveric Bio submitted the third and final part of its NDA for avacincaptad pegol, a complement C5 inhibitor, for the treatment of GA (December 2022).
Kala submitted an IND to the FDA for its KPI-012, a human mesenchymal stem cell secretome, for the treatment of persistent corneal epithelial defect (December 2022).
Melt Pharmaceuticals announced results of its phase 2 study for MELT-300, a sublingual fixed dose combination of midazolam and ketamine, for procedural sedation during cataract surgery (December 2022).
Oculis completed recruitment for the first stage of its DIAMOND Phase 3 study of its OCS-01 (dexamethasone) for the treatment of diabetic macular edema (January 2023).
Ocuphire submitted an NDA to the FDA for its phentolamine ophthalmic solution for reversal of pharmacologically induced mydriasis (December 2022). The company also started enrollment in its VEGA-2 study of phentolamine and pilocarpine for the treatment of presbyopia (January 2023).
Orasis submitted an NDA to the FDA for its CSF-1 (pilocarpine) for the treatment of presbyopia (January 2023).
Outlook Therapeutics marketing authorization application for its ONS-5010/Lytenava (bevacizumab-vikg) is now under formal review by the European Medicines Agency (December 2022).
Thea Pharma received FDA approval for its Iyuzeh™, a nonpreserved unit dose of latanoprost ophthalmic solution 0.005% for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (December 2022).
Visiox Pharma announced its NDA for its PDP-716 (0.35% brimonidine), t.i.d. for the treatment of elevated IOP, was accepted for review by the FDA (December 2022).
Gene and Cell Therapy
Genentech started a Phase 2a Study of RG6501 (OpRegen, a retinal pigment epithelial cell therapy) in patients with GA (December 2022).
Opus Genetics submitted an IND to the FDA for a phase 1/2, first-in-human clinical trial of its OPGx-001, an adeno-associated virus 8 vector, in patients with Leber congenital amaurosis (LCA) resulting from biallelic mutations in the LCA5 gene (LCA5). The company also acquired the rights to 2 preclinical-stage adeno-associated virus-based gene therapy product candidates, bestrophin-1-related and rhodopsin-mediated autosomal dominant retinitis pigmentosa, for inherited retinal diseases from Iveric Bio (December 2022).
Regulatory, Government, and Pharmaceutical Industry
Eisai received FDA approval for its Leqembi (lecanemab-irmb), an amyloid beta-directed antibody, for the treatment of Alzheimer's disease based on surrogate (imaging) data (January 2023). 1
Harm Reduction Therapeutics was granted a fast track review by the FDA for its nasal spray of naloxone (Revive™) for the treatment of opioid overdose (December 2022).
Harrow licensed the U.S. rights to from Novartis for several ophthalmic drug products (December 2022).
Perceive Biotherapeutics is developing novel gene therapies and other therapeutics for ophthalmology (January 2023).
The journal eLife will no longer make accept/reject decisions at the end of the peer review process; rather, all articles that have been peer reviewed will be published on the eLife website as Reviewed Preprints (October 2022).
The U.S. Centers for Medicare and Medicaid Services made a proposal for generic drugs to improve coverage for insurance patients (December 2022).
The U.S. Congress issued a report critical of the FDA's handling of the approval of Biogen's Alzheimer's drug Aduhelm™ (aducanumab, December 2022).
Van der Zanden et al. analyzed Dutch data regarding the level of evidence for off-label pharmacotherapies for pediatric indications. They found that if a proposed higher level of evidence were required to allow for these therapies, it would seriously limit available drug treatment for children (December 2022). 2
The FDA:
• Approved 37 new medical entities in 2022; 2 of which were ophthalmic products (Vabysmo®, faricimab-svoa; and Omlonti®, omidenepag isopropyl, December 2022).
• The Office of Oncologic Diseases published an article reviewing the accelerated approval system where a conditional approval may be given based on a surrogate end point with the requirement for longer term studies. 3 This system has undergone recent criticism, and recently a firm had to withdraw a drug that received conditional approval, but never finished a confirmatory trial. FDA provided data that the time to full approval is shorter if the sponsor has the confirmatory trial ongoing at time of conditional approval (December 2022). 4 This would improve speed; however, this requires a large investment by the sponsor before knowing the efficacy in controlled trials, and the product's approvability.
• Updated their list of off-patent off-exclusivity drugs without an approved generic including several ophthalmic products (e.g., apraclonidine, azithromycin, betaxolol, ciprofloxacin, cysteamine, dexamethasone/tobramycin, gentamicin/prednisolone acetate, natamycin, phenylephrine, trypan blue, and verteporfin, December 2022).
• Issued guidances: Laser-Assisted In Situ Keratomileusis Lasers—Patient Labeling Recommendations (July 2022), Statistical Approaches to Establishing Bioequivalence, and Homeopathic Drug Products (December 2022).
• The U.S. Congress legislated:
• The Inflation Reduction Act (HR 5376), which contains several pharmaceutical pricing controls, including a differential for biologics versus small molecules, which are of concern to the business community as to disincentivizing new product development (August 2022). 5
• The Omnibus Budget Act of 2022 (S-117), which resolved some issues relating to the Genus Decision of 2021; however, not the ophthalmic considerations (December 2022). 6 As part of that same law, the “Modernization of Cosmetics Regulation Act of 2022” will increase the reporting requirements for manufacturers of cosmetic products (December 2022).
Footnotes
Author Disclosure Statement
The author consults for numerous ophthalmic, pharmaceutical, and medical device firms. A complete listing of all of G.D.N.'s consulting affiliations can be found online.
Funding Information
No funding was received for this article.