Eyes on New Product Development: Preclinical Research

• Aerie Pharmaceuticals received a positive vote from an FDA Advisory Committee meeting for its netarsudil (Rhopressa) for the treatment of elevated intraocular pressure (IOP) (October 2017), which was approved by the FDA for the treatment of elevated intraocular pressure in patients with open-angle glaucoma and ocular hypertension (December 2017).* Aerie also acquired from Envisia the rights to use PRINT^® technology, a drug delivery system in ophthalmology (October 2017).*

• Aldeyra Therapeutics presented results from trials of molecules that trap aldehydes: ADX-102 for the treatment of dry eye and allergic conjunctivitis and ADX-103 for retinal disease (October 2017). The firm also announced results of a phase 2 clinical trial evaluating topical ocular reproxalap in patients with noninfectious anterior uveitis (November 2017).

• Allergan reached an agreement regarding patent disputes on Restasis^® with InnoPharma, Inc. (October 2017).

• Aurinia Pharmaceuticals announced plans to evaluate its proprietary nanomicellar voclosporin ophthalmic solution for the treatment of keratoconjunctivitis sicca (October 2017).

• Bausch + Lomb and Nicox received U.S. FDA approval for Vyzulta (latanoprostene bunod) for the treatment of elevated IOP in patients with open-angle glaucoma and ocular hypertension (November 2017).* The firm also received U.S. FDA approval for Lumify (brimonidine ophthalmic solution 0.025%), an over-the-counter eye drop for the treatment of conjunctival hyperemia (December 2017).

• BioTime announced its evaluation of a system for vision restoration program for advanced retinal diseases and injuries (September 2017).

• Clearside Biomedical completed enrollment in a TYBEE, a phase 2 trial of CLS-TA, triamcinolone acetonide used together with intravitreally administered EYLEA^® (aflibercept) for the treatment of diabetic macular edema (October 2017).*

• EyeGate completed enrollment in its phase 2b study of EGP-437 for postoperative pain and inflammation (November 2017).

• Eyenovia presented results for its phase 2 study of EYE-102, a piezo-ejection ocular microdosing system for phenylephrine for mydriatic treatment (October 2017).

• Gemini Therapeutics is advancing several programs to treat genetically defined dry age-related macular degeneration (October 2017).

• Genentech reported results of its 2 phase 3 studies of intravitreal (IVT) lampalizumab in the treatment of geographic atrophy (September–November 2017).*

• Imprimis plans to offer a compounded form of cyclosporine ophthalmic emulsion (October 2017). The firm also is launching Surface Pharmaceuticals, a subsidiary that is developing 3 drug candidates for up to 5 indications for ocular surface diseases, including dry eye and blepharitis (October 2017).

• InMed is developing a topical hydrogel nanoparticle formulation of a cannabinoid (October 2017).

• Iveena received orphan status designation from the FDA for its IVMED-80, a daily eye drop for keratoconus (November 2017).

• Kala Pharmaceuticals submitted a new drug application (NDA) to the FDA for Inveltys™ (KPI-121 1%), a twice daily formulation of loteprednol etabonate for the treatment of inflammation and pain in patients who have undergone ocular surgery (October 2017).

• Nevakar started enrollment in its phase 3 trial of its topical NVK-002 to slow myopia in children. The nature of the molecule has not been disclosed (November 2017).

• Nicox entered into an exclusive licensing agreement with Eyevance Pharmaceuticals for the commercialization of Zerviate™ (cetirizine ophthalmic solution) in the United States (September 2017). Nicox and pSivida entered into a collaboration agreement to explore the potential of combining Nicox's nitric oxide (NO)-donating compounds with pSivida's bioerodible sustained-release drug delivery system for the treatment of glaucoma and ocular hypertension (October 2017). Nicox SA and Re-Vana Therapeutics entered into a research collaboration to explore combining Nicox's stand-alone NO donors with Re-Vana's EyeLief photo crosslinked biodegradable drug delivery platform for the reduction of IOP (October 2017).

• Novaliq obtained European regulatory approval for its NovaTears^®+Omega-3 for the treatment of evaporative dry eye disease (December 2017).

• Novartis announced results of a comparison study of brolucizumab (RTH258) versus aflibercept in the treatment of wet age-related macular degeneration (AMD) (November 2017).

• Ocugen received FDA orphan drug designation for OCU300 (brimonidine) to treat ocular graft-versus-host disease (August 2017). The firm also obtained a license from the Massachusetts Eye and Ear Infirmary for a novel gene therapy platform for nuclear hormonal receptors for retinal disease (December 2017).

• Omeros received U.S. FDA approval for a supplemental indication for Omidria^® (phenylephrine and ketorolac intraocular solution) in pediatric patients (December 2017).

• Oyster Point Pharmaceuticals is developing pharmacotherapies for dry eye and other diseases of the ocular surface (November 2017).

• Realm Therapeutics began enrollment in its phase 2 study of PR013, a topical ophthalmic formulation of high concentration hypochlorous acid, for the treatment of allergic conjunctivitis (December 2017).

• Regeneron's supplemental biologics license application for a 12-week dosing interval of EYLEA (aflibercept) for patients with wet age-related macular degeneration was accepted for review by the FDA (December 2017).

• Santen submitted a marketing authorization application to the Japanese Ministry of Health, Labour and Welfare for DE-117 (Omidenepag isopropyl) for the treatment of glaucoma and ocular hypertension. DE-117 is a selective EP2 receptor agonist (November 2017). The firm also received a complete response letter from the FDA for its NDA for IVT sirolimus (DE-109) for the treatment of noninfectious posterior uveitis (December 2017).

• SciFluor announced results of a phase 1/2 trial of its integrin antagonist SF0166 eye drops in the treatment of wet AMD (December 2017).

• Spark Therapeutics received a favorable review by an FDA advisory committee for its RPE-65 gene therapy, Luxturna (voretigene neparvove) for the treatment of vision loss in patients with confirmed biallelic RPE65-mediated inherited retinal disease (October 2017). This product was subsequently approved by the FDA (December 2017).

• Thrombogenics stopped enrollment in a trial of ocriplasmin for nonproliferative diabetic retinopathy due to slow enrollment rate (December 2017).

• Glaukos submitted a premarket approval application to the FDA for its iStent injectable trabecular microbypass stent, according to a company press release. This product contains 2 heparin-coated titanium stents preloaded into an autoinjection system (December 2017).

• Pixium received authorization to start clinical trials in France with its PRIMA miniaturized, wireless, subretinal implant to restore vision in patients affected by retinal dystrophies (October 2017).

• Ivantis submitted a final premarket approval module to the FDA for its Hydrus microstent to lower IOP in open-angle glaucoma (November 2017)

• Johnson and Johnson Vision is acquiring TearScience through its Abbott Medical Optics (August 2017).

• RxSight™ received U.S. FDA approval for its RxSight light adjustable lens and the light delivery device. This product allows adjustment of an intraocular lens refraction after implantation (November 2017).

• SecondSight received expedited access designation for its Orion™ cortical visual prosthesis system for the treatment of patients with no light perception (November 2017).

• The American Academy of Ophthalmology urged the FDA to put an ophthalmologist in charge of ophthalmic drug reviews (October 2017).

• The American Medical Association adopted a new strategy that allows for more consistent coverage of genomic and genetic tests and precision medicine (November 2017).

• AstraZeneca disclosed that Acerta, a firm in which it invested in 2015, falsified preclinical pharmacology data on the oncology treatment, acalabrutinib (October 2015). Note that pharmacology data typically do not have to meet the standards of good laboratory practice.

• British drug industry trade association dropped its legal challenge to new guidelines from national regulators that subject higher priced drugs to an extra review under England's single-payer National Health Service (October 2017).

• The European Medicines Agency, currently located in London, will be moving to Amsterdam as a consequence of Brexit (November 2017).

• Measles virus has been eliminated from the United Kingdom according to the World Health Organization (September 2017).

• Merck was asked by the French National Agency for Medicines and Health Products Safety to return to market its Levothyrox^® (levothyroxine sodium) that the company had phased out and replaced with a new formulation 6 months ago. This was based upon adverse events reported with the new formulation (September 2017). The firm also received U.S. FDA approval for Prevymis^® (letermovir) by both the oral and intravenous route indicated for the prevention of cytomegalovirus (CMV) infection in patients undergoing stem cell transplant (November 2017).

• Otsuka received approval from the FDA for a modification of its aripiprazole antipsychotic oral drug to include an imbedded sensor to monitor treatment adherence (November 2017).

• ResearchGate, an academic social gate, was served notice by a coalition of publishers to remove up to 7 million posted copyrighted articles (October 2017).

• Several U.S. states accused key players in the generic drug industry of a broad price-fixing conspiracy (September 2017).

• The National Academy of Science published a report on drug pricing in the United States. Among their recommendations are for the federal government to consolidate and apply its purchasing power to directly negotiate prices with the producers and suppliers of medicines, and strengthen formulary design and management, improve methods for assessing the value that drugs provide, ensure that incentives to develop drugs for rare diseases are not extended to widely sold drugs, and greater disclosure on financial issues (November 2017). ³

• U.S. FDA issued a warning over cannabis-based therapies that promise the ability to cure cancer (February 2017). The FDA also reported an adverse event related to off-label, pharmacy compounded prophylactic use of intraocular triamcinolone, moxifloxacin, and vancomycin (October 2017). The FDA will recognize good manufacturing practices (GMP) inspections by eight European regulators for products to be sold in the United States; expanded its “Navigator,” a system for finding investigational medications for rare, debilitating, and sometimes fatal diseases; and is actively working with drug manufacturers to address critical shortages of intravenous fluids aggravated by Hurricane Maria's impact on Puerto Rican drug manufacturing facilities (November 2017). The FDA issued a warning letter to a manufacturing of homeopathic drugs claiming ophthalmic indications for manufacturing issues, as well as published a guidance on a risk-based enforcement approach to homeopathic drugs. FDA also published a draft guidance on developing target therapies in low frequency molecular subsets of a disease in an effort to address new drugs being developed based solely on their ability to target these underlying molecular subtypes, and published a list of the 8 approved biosimilar products, starting with Zarxio^® (Filgrastim-sndz) in March 2015 (December 2017).

• U.S. Senator Amy Klobuchar (D MN) introduced S 2042, a bill to reduce drug waste that includes the issue of drop size. In a related action, a class action suit alleging wasteful packaging of ocular medication was reinstated (October 2017). The “Tax Cuts and Jobs Act” tax bill passed by the U.S. Congress and signed into law (HR-1) substantially reduces the tax credit for orphan drugs (December 2017).

• California passed SB512 regarding disclosure by health practitioners regarding unapproved stem cell therapy disclosures (October 2017).