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`FDA Approves Lucentis (ranibizumab) for the
`Treatment of Wet Age-Related Macular
`Degeneration
`South San Francisco, Calif. -- June 30, 2006 -- Genentech, Inc. (NYSE: DNA) announced today that
`the U.S. Food and Drug Administration (FDA) has approved Lucentis
`(ranibizumab injection) for
`the treatment of neovascular (wet) age-related macular degeneration (AMO). The FDA approved
`Lucentis after a Priority Review (six-month). Genentech will ship product today. Nearly all patients
`(95 percent) treated with Lucentis maintained their vision in the Phase Ill clinical trials. Vision
`improved by at least three lines ( or 15 letters) on the study eye chart in up to 40 percent of these
`patients at one year. Lucentis is designed to inhibit the formation and leakage of new blood vessels
`in the back of the eye, the primary cause of central vision loss associated with this disease.
`
`"Lucentis provides new hope for patients with wet AMO because it is the first therapy to provide a
`benefit in vision for a significant number of patients," said Arthur D. Levinson, Ph.D., Genentech's
`chairman and chief executive officer. "We are proud that the seminal work in angiogenesis
`conducted at Genentech, years of clinical study, and the dedication and commitment of thousands
`of patients and retina specialists have all contributed to this important approval."
`
`"In my opinion, the Lucentis approval stands out as one of the most important medical
`developments in ophthalmology during my 25 years in the field because it has the potential to
`reverse vision loss associated with wet AMO," said Eugene de Juan, M.D., president, American
`Society of Retina Specialists. "We are pleased that Lucentis has been approved by the FDA and
`look forward to working with Genentech to provide retina specialists in the United States with
`access to Lucentis for patients as quickly and smoothly as possible."
`
`The FDA approval of Lucentis is based on data from two large Phase Ill clinical trials (MARINA and
`ANCHOR). In these studies:
`
`• Nearly all patients (approximately 95 percent) treated with Lucentis (0.5 mg) maintained
`(defined as the loss of less than 15 letters in visual acuity) and up to 40 percent improved
`(defined as the gain of 15 letters or more in visual acuity) vision at one year, as measured on
`the Early Treatment of Diabetic Retinopathy (ETDRS) eye chart.
`
`• On average, patients treated with Lucentis in the MARINA study experienced an improvement
`from baseline of 6.6 letters at two years compared to a loss of 14.9 letters in the sham group. In
`the ANCHOR study, patients treated with Lucentis, on average, experienced an 11.3 letter gain
`
`https://www.drugs.com/newdrugs/fda-approves-lucentis-ranibizumab-wet-age-related-macular-degeneration-327.html
`
`Novartis Exhibit 2266.001
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`from baseline at one year compared to a loss of 9.5 letters in the Visudyne® photodynamic
`therapy (PDT) control group.
`
`Up to 40 percent of patients treated with Lucentis achieved vision of 20/40 or better. In addition to
`data from the two pivotal studies, data from the Phase 1/11 FOCUS and Phase lllb PIER studies
`were included in the FDA review.
`
`Lucentis 0.5 mg is recommended for intravitreal injection once a month. If monthly injections are not
`feasible, treatments can be reduced to one injection every three months after the first four monthly
`injections. Compared to continued monthly dosing, dosing every three months will lead to an
`approximate five-letter (one-line) loss of visual acuity benefit, on average, over the following nine
`months. Patients should be evaluated regularly.
`
`"Now that Lucentis is approved, we will continue to work with the retina community to evaluate how
`patients may be able to benefit from less frequent dosing, as emerging clinical data indicate that
`dosing may need to be tailored to individual patient needs," said Levinson.
`
`In clinical trials, the most common adverse reactions among patients treated with Lucentis (reported
`in at least 6 percent more patients than in the control groups in at least one study) included
`conjunctiva! hemorrhage, eye pain, vitreous floaters, increased intraocular pressure and intraocular
`inflammation. Although there was a low rate (less than 4 percent) of arterial thromboembolic events
`(ATEs) observed in the Lucentis clinical trials that was not statistically different between the Lucentis
`and control groups, there is a theoretical risk of ATEs following intravitreal use of inhibitors of VEGF.
`Serious adverse events related to the injection procedure occurred in less than 0.1 percent of
`intravitreal injections, including endophthalmitis, retinal detachments and traumatic cataracts. Other
`serious ocular adverse events observed among Lucentis-treated patients (that occurred in less than
`2 percent of patients) included intraocular inflammation and increased intraocular pressure. Lucentis
`is contraindicated in patients with hypersensitivity and ocular or periocular infections.
`
`"The impact of wet AMO goes beyond vision loss and can affect a person's ability to interact with
`family and friends, conduct daily activities and, overall, maintain their independence," said Dr.
`Stephen Rose, chief research officer at the Foundation Fighting Blindness. "As an organization
`dedicated to research for preventions, treatments and cures for people affected by retinal
`degenerative diseases, we applaud the FDA's approval of Lucentis as an important advancement in
`the treatment of wet AMO."
`
`Lucentis was specifically developed for intraocular use in the eye to treat the underlying cause of
`wet AMO by targeting the molecular pathway that controls the formation of new blood vessels.
`Lucentis is designed to bind and inhibit VEGF-A, a protein that is believed to play a critical role in
`angiogenesis (the formation of new blood vessels).
`
`https://www.drugs.com/newdrugs/fda-approves-lucentis-ranibizumab-wet-age-related-macular-degeneration-327.html
`
`Novartis Exhibit 2266.002
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`About Lucentis
`
`(ranibizumab injection) (0.5 mg) is approved for the treatmentof patients with
`Lucentis
`neovascular (wet) AMD. Lucentis is a recombinant humanized IgG1 kappaisotype therapeutic
`antibody fragment developed for intraocular use. Lucentis binds to and inhibits the biologic activity
`of human vascular endothelial growth factor A (VEGF-A), a protein that is believed to playa critical
`role in angiogenesis (the formation of new blood vessels). VEGF-A has been shownto lead to wet
`AMD diseaseprogression and central vision loss. Lucentis was developed by Genentech and the
`Novartis Ophthalmics Business Unit for diseases or disorders of the eye. Genentechretains
`commercial rights in the United States and Novartis has exclusive commercial rights for the rest of
`
`the world.
`
`About AMD
`
`AMD is a major cause of painless central vision loss and is a leading cause ofblindness in people
`over 55. The National Eye Institute estimates that there are 1.7 million people with the advanced
`form of AMD in the United States alone and that this prevalencewill grow to 2.95 million by 2020.
`AMD occursin two forms: dry and wet.
`
`The dry form is associated with atrophic cell death of the central retina or macula, which is required
`for fine vision used for activities such as reading, driving or recognizing faces. The wet form is
`caused by growth of abnormal blood vessels, also knownas choroidal neovascularization (CNV) or
`ocular angiogenesis, under the macula. These vessels leak fluid and blood and causescar tissue
`that destroys the central retina. This process results in a deterioration of sight over a period of
`monthsto years.
`
`About Angiogenesis
`
`Genentechis a leader in research and product developmentin the area of angiogenesis, the
`process by which newblood vessels are formed. In 1989, NapoleoneFerrara, M.D., and a team of
`scientists at Genentech conducted seminal work in the field, which resulted in the identification and
`
`cloning of a gene termed Vascular Endothelial Growth Factor (VEGF), now known as VEGF-A. The
`VEGF-Aprotein is believed to play a critical role in angiogenesis and serves as oneof the key
`contributors to physiological or pathological conditions that can stimulate the formation of new blood
`vessels. The processof angiogenesis is normally regulated throughout developmentand adultlife,
`and the uncontrolled growth of new blood vessels is an important contributor to a numberof
`pathologic conditions, including wet AMD.
`
`Genentech's Commitment to Patient Access
`
`Genentech is committed to assisting eligible patients in accessing our therapies for approved
`indications, regardlessoftheir ability to pay. Although Genentech's products are covered by most
`government and private insurance, Genentech established the Genentech® Access to Care
`
`Novartis Exhibit 2266.003
`Regeneron v. Novartis, IPR202 1-008 16
`
`Novartis Exhibit 2266.003
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`Foundation (GATCF)in 1990for its marketed products, and donatesfree productto eligible
`uninsured patients in the United States, except for Pulmozyme® (dornase alfa, recombinant), which
`is covered by the Genentech Endowmentfor Cystic Fibrosis. In 2005 alone, GATCF supported over
`18,000 patients by providing approximately $200 million of free product. Genentech recently
`donated more than $27 million to several independent public charities that provide financial
`assistanceto eligible patients who cannot access needed medical treatment due to co-pay costs. To
`learn more about these independent, public charities and potential financial assistance options,
`
`patients can speak with an Alternative Funding Specialist from Genentech's Single Point of Contact
`(SPOC)group bycalling 866-724-9394orvisiting http://www.SPOConline.com.
`
`About Genentech
`
`Founded 30 years ago, Genentechis a leading biotechnology companythat discovers, develops,
`manufactures and commercializes biotherapeutics for significant unmet medical needs. A
`considerable numberof the currently approved biotechnology products originated from or are based
`on Genentech science. Genentech manufactures and commercializes multiple biotechnology
`products and licenses several additional products to other companies. The company has
`headquarters in South San Francisco, California andis listed on the New York Stock Exchange
`under the symbol DNA.Foradditional information about the company,pleasevisit
`http://www.gene.com.
`
`This press release contains a forward-looking statement regarding the shipping timeframe for
`LUCENTIS. Such statementis a prediction andinvolvesrisks and uncertainties such that the actual
`result maydiffer materially. Among other things, the shipping timeframe for Lucentis could be
`affected by unexpected delays in preparation offinished product for shipping or in delivery of
`finished product to shippers. Please also refer to Genentech's periodic reports filed with the
`
`Securities and Exchange Commission. Genentech disclaims, and does not undertake, any
`obligation to update or revise any forward-looking statementin this press release.
`
`Source: Genentech, Inc.
`
`Posted: June 2006
`
`Related Articles:
`
`e FDA Approves Genentech’s Lucentis (ranibizumab injection) 0.3 mg Prefilled Syringe for
`Diabetic Macular Edema and Diabetic Retinopathy - March 21, 2018
`
`e FDA Approves Genentech’s Lucentis (ranibizumab) for all Forms of Diabetic Retinopathy - April
`
`17, 2017
`
`Novartis Exhibit 2266.004
`Regeneron v. Novartis, IPR202 1-008 16
`
`Novartis Exhibit 2266.004
`Regeneron v. Novartis, IPR2021-00816
`
`

`

`e FDA Approves Genentech’s Lucentis (ranibizumab) for Myopic Choroidal Neovascularization-
`January 5, 2017
`
`e FDA Approves Genentech’s Lucentis (ranibizumab)Prefilled Syringe - October 14, 2016
`
`e FDA Approves Lucentis (ranibizumab) to Treat Diabetic Retinopathy in People with Diabetic
`Macular Edema - February 6, 2015
`
`e FDA Approves Lucentis (ranibizumab) for Treatment of Diabetic Macular Edema (DME)-
`August 10, 2012
`
`e FDA Approves Lucentis (ranibizumab) for the Treatment of Macular Edema Following Retinal
`Vein Occlusion - June 23, 2010
`
`e Genentech Submits Biologics License Application for FDA Review of Lucentis in Wet Age-
`Related Macular Degeneration - December 30, 2005
`
`Lucentis (ranibizumab) FDA Approval History
`
`Novartis Exhibit 2266.005
`Regeneron v. Novartis, IPR202 1-008 16
`
`Novartis Exhibit 2266.005
`Regeneron v. Novartis, IPR2021-00816
`
`