Nepafenac
NSAID analgesic and anti-inflammatory drug
From Wikipedia, the free encyclopedia
Nepafenac, sold under the brand name Nevanac among others, is a nonsteroidal anti-inflammatory drug (NSAID), usually sold as a prescription eye drop 0.1% solution (Nevanac) or 0.3% solution (Ilevro). It is used to treat pain and inflammation associated with cataract surgery.[3] Nepafenac is a prodrug of amfenac, an inhibitor of COX-1 and COX-2 activity.[4][5]
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| Trade names | Nevanac, Ilevro, Amnac, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a606007 |
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| Routes of administration | Topical eye drops |
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| ECHA InfoCard | 100.207.414 |
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| Formula | C15H14N2O2 |
| Molar mass | 254.289 g·mol−1 |
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Medical uses
Pharmacology
Adverse events
Side effects include headache; runny nose; pain or pressure in the face; nausea; vomiting; and dry, itchy, sticky eyes.[9] Serious side effects include red or bloody eyes; foreign body sensation in the eye; sensitivity to light; decreased visual acuity; seeing specks or spots; teary eyes; or eye discharge or crusting.[9]
Regulatory
Nevanac
On February 25, 2005, Alcon filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for Nevanac 0.1%.[10] Results from the two trials referenced in the NDA (Phase 2/3 study C-02-53; Phase 3 study C-03-32) have not been published.[11] Study C-02-53 consisted of 228 patients across 10 centers in the United States.[12] Study C-03-32 consisted of 522 patients across 22 centers in the United States.[12] The efficacy results presented were confirmed in a study published in 2007.[13]
Nevanac was approved by the FDA on August 19, 2005, with application number 021–862.[14]
Ilevro
An NDA for Ilevro was filed on December 15, 2011.[15] In a one-month study, no new toxicities arose in the new formulation of nepafenac.[16] Safety and efficacy information was derived from the previous Nevanac application.[16] In June 2010, a confirmatory study began (Study C09055) consisting of over 2000 patients from 49 US sites and 37 European sites.[17][18] A second phase 3 trial (Study C11003) was conducted in a population of 1,342 patients at 37 sites across the United States which failed to demonstrate superiority over Nevanac in an altered dosing regimen.[17]
Ilevro was approved by the FDA on October 16, 2012, with application number 203–491.[19]
Commercialization
Both Nevanac and Ilevro are manufactured and sold by Alcon, Inc.[6][7] Alcon is currently a division of Novartis International AG, which is primarily based out of Switzerland.[20] Alcon, Inc. also holds locations in both Switzerland and the United States.[21] The company has gone through several name changes, from Alcon Laboratories, Inc. to Alcon Universal, Ltd., to Alcon, Inc.[21]
Nevanac entered the market in 2005 as a product of Alcon, at the time a subsidiary of Nestlé.[22] On April 6, 2008, Novartis agreed to purchase approximately 74 million shares of Alcon from Nestlé at $143.18 per share.[22] On January 4, 2010, Novartis agreed to purchase all remaining shares of Alcon from Nestlé, totalling 156 million shares or 77% of the shares in the company.[22] At the time of the purchase, a proposal for a merger under Swiss merger law was given to the Alcon board of directors.[22] The merger was agreed upon on December 15, 2010, making Alcon "the second largest division within Novartis."[22] The merger was completed on April 8, 2011.[23]
Ilevro was launched by Alcon on January 21, 2013.[24] In 2014 and 2015, net sales by Alcon grew, contributed to in part by the increased volume in sales of Ilevro.[25][26][27] That financial year, Novartis reported $18 billion in total financial debt.[25] That figure has grown steadily since. In 2016, Novartis reported a total debt of $23.8 billion,[28] up from the $21.9 billion reported in 2015 [27] and the $20.4 billion reported in 2014.[26] As of May 2017, Novartis is estimated to be worth $193.2 billion.[29]
On January 27, 2016, Alcon was moved to become a branch of the Innovative Medicines Division at Novartis.[28] Early in 2016, Alcon formed agreements with both TrueVision and PowerVision, and acquired Transcend Medical.[28] As of January 2017, Novartis is weighing options for Alcon in the business structure.[28]
Commercial risks
Alcon faced declining growth in 2016, having faced challenges in development and marketing of new products.[28]
Marketing
Novartis maintains a detailing unit geared toward health professionals consisting of over 3,000 employees within the United States and an additional 21,000 worldwide.[28] Novartis is also seeking to expand direct-to-consumer advertising and entrance into specialty product markets.[28] Novartis also notes the influence of position and preference on US Centers for Medicare & Medicaid formularies in expanding their market value.[28]
Nepafenac, Nevanac, and Ilevro are all absent from the 2016 Annual Report issued from Novartis.[28]
Intellectual property
There are currently[when?] seven U.S. patents filed that are directly associated with the modernized formulations of nepafenac, all stemming from Novartis.[30] There are three patents associated with Nevanac that are still[when?] active[31] and four associated with Ilevro.[32] The earliest patent related to the modern formulations of nepafenac was approved on June 11, 2002, after being filed in 1999, by Bahram Asgharian.[33] A patent was filed by Warren Wong, associated with Alcon, Inc. based out of Fort Worth, Texas, on December 2, 2005, for aqueous suspensions of nepafenac.[34] Another patent for a nepafenac-based drug was filed on May 8, 2006, by Geoffrey Owen, Amy Brooks, and Gustav Graff.[35] A patent was filed by Masood A. Chowhan and Huagang Chen on February 9, 2007, and approved on May 24, 2011,[36] followed closely by a patent filed by Warren Wong on September 23, 2010, and approved on December 6, 2011.[37] Masood A. Chowhan, Malay Ghosh, Bahram Asgharian, and Wesley Wehsin Han filed another patent on December 1, 2010, and approved on December 30, 2014.[38] The most recent[when?] patent was filed by Masood A. Chowhan, Malay Ghosh, Bahram Asgharian, and Wesley Weshin Han on November 12, 2014, and approved on May 30, 2017.[39] These patents are in effect until dates ranging between July 17, 2018, and March 31, 2032.[32]
Novartis also maintains patents on nepafenac in 26 countries outside the United States.[40]
