ranibizumab - Lucentis; vascular endothelial growth factor monoclonal antibody fragment, recombinant
Status: BLA recently approved; pending in EU
Organizations involved:
Genentech, Inc. – Manuf.; R&D; Tech.; USA mark.; Patent dispute
Novartis AG – Intl. mark.; US mark. (specific indication)
Protein Design Ltd. – Tech.
Xoma Corp. – Tech.
Amgen Inc. – Tech.
Dastgheib, Dr. – Patent dispute
MedImmune, Inc. - Patent dispute
AstraZeneca plc - Parent
Cross ref.: See the entry above concerning Avastin also from Genentech for biological and other information related to VEGF and its inhibition.
Description: Lucentis is an aqueous formulation of ranibizumab, a Fab fragment of a recombinant humanized IgG1 kappa isotype murine monoclonal antibody with binding specificity for vascular endothelial growth factor (VEGF-A) expressed by transformed Escherichia coli (E. coli) bacteria. Ranibizumab has a molecular mass of 48 kDa.
Lucentis is packaged as a preservative-free, sterile solution in single-use glass vials designed to deliver 0.05 mL of 10 mg/mL ranibizumab aqueous solution with 10 mM histidine HCl; 10% alpha,alpha-trehalose dihydrate; and 0.01% polysorbate 20; at pH 5.5. Each carton contains one 2-cc glass vial of ranibizumab, one 5-micron (µ), 19-gauge x 1-1/2-inch filter needle for withdrawal of the vial contents, one 30-gauge x 1/2-inch injection needle for the intravitreal injection, and a package insert. Vials are for single eye use only.
Nomenclature: VEGF Mab Fab, rDNA [BIO]; ranibizumab [USAN]; immunoglobulin G1, anti-(human vascular endothelial growth factor) Fab fragment (human-mouse monoclonal rhuFAB V2 g1-chain), disulfide with human-mouse monoclonal rhuFAB V2 light chain [CAS]; 347396-82-1 [CAS RN]; vascular endothelial growth factor monoclonal antibody Fab fragment, recombinant [SY]; rhuFabV2 [SY]; NDC 50242-080-01 [NDC]
Biological.: Ranibizumab, like bevacizumab (see preceding entry for Avastin), exhibit anti-angiogenesis activity, i.e., halts or slows growth of new blood vessels. Lucentis was specifically developed for intraocular use in the eye to treat the underlying cause of wet AMD by targeting the molecular pathway that controls the formation of new blood vessels associated with wet AMD. Ranibizumab binds and inhibits VEGF-A, a protein that is believed to play a critical role in angiogenesis.
Companies.: Lucentis was developed by and is manufactured and marketed in the U.S. and North America by Genentech, now fully part of Hoffmann-La Roche. Novartis Ophthalmics Business Unit, Novartis AG, has exclusive commercialization rights for the rest of the world.
Genentech has as number of facilities where Lucentis may be manufactured. Besides major U.S. facilities, this includes a 1,000-liter E.coli manufacturing facility in Singapore expected to receive FDA licensure for bulk drug production of Lucentis in 2010 (with this not part of the Singapore facilities acquired from Lonza for manufacture of Avastin).
In Jan. 2010, Novartis expanded its eye health operations, acquiring Alcon eye care and creating a new Novartis division that incorporated CIBA Vision and a number of Novartis' ophthalmic medicines.
Genentech's existing 1,000-liter E.coli manufacturing facility in Singapore was expected to receive FDA licensure for bulk drug production of Lucentis (ranibizumab) in 2010.
In Aug. 2012, Genentech/Roche granted Novartis U.S. marketing rights for Lucentis to treat diabetic macular edema,
Manufacture: Ranibizumab is produced by an E. coli expression system in a nutrient medium containing the antibiotic tetracycline. Tetracycline is not detectable in the final product.
FDA class: Biologic BLA
Approvals: Date = 20060630; BLA (BL125156)
Date = 20100623; BLA supplement; Indication = treatment of macular edema following retinal vein occlusion (RVO; with 6-month Priority Review)
Date = 20120810; BLA supplement; Indication = treatment of diabetic macular edema (DME)
Indications: [full text of the "INDICATIONS AND USAGE” section of product insert/labeling, 8/12/2012]:
LUCENTIS is indicated for the treatment of patients with:
1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD)
1.2 Macular Edema Following Retinal Vein Occlusion (RVO)
1.3 Diabetic Macular Edema (DME)
Status: The BLA was submitted on Dec. 30, 2005, requesting approval for treatment of neovascular wet age-related macular degeneration (AMD). It was accepted on March 1, 2006 with priority review (6 month review target date of June 30, 2006). The BLA had been denied “fast-track” status, which allows for a rolling submission of sections of the BLA as they are completed, but this was not expected to affect the timetable for the BLA’s review. The BLA was approved on June 30, 2006. Final labeling includes the results of the PIER study, which supported a less frequent dosing (quarterly) regimen, submitted to FDA in May 2006. Lucentis was the first product approved by FDA with physician labeling following the agency’s new format.
On Jan. 24, 2007, the European Union granted approval (MAA) for Lucentis treatment of wet age-related macular degeneration (AMD). At the time, Lucentis was approved for wet AMD in Switzerland, India and the U.S. and Novartis was awaiting regulatory approval in Australia.
In Jan. 2007, Genentech issued a warning (dear doctor) letter to eyecare specialists regarding Lucentis use associated with increased risk for stroke. Preliminary data from the SAILOR trial showed that 1.2% of patients given high dose of Lucentis (0.5 mg per injection; the approved dose) had a stroke, compared with 0.3% of those treated with a low dose of 0.3 mg. Patients having previously experienced a stroke had a higher risk of a subsequent stroke. Differences between the doses did not seem to affect the rates of heart attacks and vascular death. Overall, the results were consistent with completed Phase III studies. The increased risk of strokes was not really new or unexpected, and there was no change in Lucentis’ labeling.
In June 2011, the European Union granted Novartis a new indication for Lucentis -- treatment of patients with visual impairment caused by diabetic macular edema (DME).
In June 2011, the European Union granted Novartis a new indication for Lucentis -- treatment of patients with visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO and central RVO), a sudden-onset disease where patients have difficulties with daily activities such as reading, cooking and driving. Lucentis became the first anti-VEGF therapy licensed for the treatment of both branch- and central-RVO in the European Union, having demonstrated in pivotal trials that it improves vision and vision-related quality of life for these patients.
On July 26, 2012. tje Dermatologic & Ophthalmic Drugs Advisory Committee (DODAC), FDA, voted unanimously (10-0) to recommend approval of the 0.3 mg dose of Lucentis for treatment of diabetic macular edema (DME). The majority of DODAC (8-2) also recommended the 0.5 mg dose.
On July 5, 2013, the European Commission granted Novartis supplementa approval for Lucentis for treatment of visual impairment due to choroidal neovascularisation secondary to pathologic myopia.
Tech. transfer: Genentech has licensed monoclonal antibody humanization technology from Protein Design Ltd. (PDL) in connection with Lucentis. See the Monoclonal Antibody Products entry (#300) for further information about this and Genentech’s own broadly-enabling recombinant monoclonal antibody technology, including highly controversial Cabilly-Boss patents.
Genentech has nonexclusively licensed Bacterial cell expression technology (BCE) from Xoma Corp. This involves use of the araB promoter for expression and secretion of antibody domains from bacteria (E. coli) as properly folded, functional proteins. XOMA was the first to demonstrate the secretion of antibody domains directly from bacterial cells as fully functional, properly folded molecules. XOMA has received ten U.S. patents to date relating to aspects of its BCE system, including six patents that broadly cover the secretion of immunoglobulins from bacteria, including antibody fragments such as Fab and single-chain antibodies. Royalty rates for Lucentis are reported to be slightly less than 1%. Lucentis is the first marketed product using this technology. Xoma receives an estimated <1% royalty on Lucentis sales.
In Nov. 2006, a U.S. District Court jury found in favor of Genentech in a suit brought by Dr. Kourosh Dastgheib, an ophthalmologist who has accused Genentech of reneging on a promise to pay him 1% royalties on Lucentis sales in exchange for his research slides of human eye specimens. Dr. Dastgheib had sought over $1.2 billion, but the jury gave him nothing. He likely lost, because absolutely no corroborating evidence was presented.
In Dec. 2009, Novartis submitted a MAA supplment seeking a new indication -- diabetic macular edema (DME). Visual impairment due to DME affects 1–3% of diabetics worldwide and is a rare but serious complication of diabetes that can lead to significant vision loss.
In Aug. 2010, Genentech, now fully part of Hoffmann-La Roche, informed PDL BioPharma Inc. it believes that four of its marketed products, including Lucentis, are not covered by patents that had been licensed by Genentech from PDL. Genentech/Roche plans to continue to pay patent royalties (while presumably trying to renegotiate of get out of its prior licensing agreement). PDL will surely appeal any actions by Genentech/Roche, since is receives 30% of its revenue from these licenses. Genentech licensed antibody technology from PDL in 1998 and it pays royalties to PDL on sales of Herceptin, Avastin, Lucentis, and Xolair. Genentech planned to continue making royalty payments on those product sales in the U.S. during the resolution of this dispute.
In Oct. 2009, MedImmune/AstaZeneca filed a patent infringement suit in relation to tis EU patent,l EP0774511 and EP2055777, against Novartis and the U.K. Medical Research Council (MRC) in the UK High Court of Justice (Patents Court) alleging patent infringement by Lucentis. Novartis counterclaimed for revocation of the asserted patents. The Court in May 2011 held, among other things, that the asserted patents were invalid as none of the asserted claims of the patent were entitled to priority from the priority documents. The Court also held that Novartis did not infringe any of the patents, had they been valid, as the active ingredient was not produced by a process disclosed in the claims of the asserted patents. Similar cases were also files in countries including France, Germany, the Netherlands and Switzerland (apparently, with no positive outcome for MedImmune).
Trials: To date, Lucentis is the only therepautic shown in trials to in any way reverse wet AMD and improve vision, while Macugen (see related entry) has only been shown to slow progression. However, Lucentis can not be expected to fully restore vision, e.g. to 20:20. Overall in its Phase III trials, nearly all patients (95%) treated with Lucentis maintained their vision; and vision improved by at least three lines (or 15 letters) on the study eye chart in up to 40% of responding patients at one year.
The initial BLA submission for Lucentis was based on one-year clinical efficacy and safety data from two pivotal Phase III trials, ANCHOR and MARINA, as well as one-year clinical data from the Phase I/II FOCUS trial. These studies demonstrated that Lucentis is the first investigational therapy to impr ove vision in patients with wet AMD in two pivotal Phase III trials. Also, Lucentis is the first investigational therapy to demonstrate a clinical benefit compared to Visudyne photodynamic therapy (PDT; verteporfin from QLT Inc. and Novartis AG) in a head-to-head clinical study (ANCHOR). Genentech will submit complete two-year data from the Phase III MARINA study to support its BLA.
In Nov. 2005, preliminary 1-year data were reported from the ongoing, 2-year, double-blind, international Phase III ANCHOR trial in 423 patients. ANCHOR study met its primary efficacy endpoint of maintaining vision, defined as a loss of less than 15 letters in visual acuity on the Early Treatment of Diabetic Retinopathy (ETDRS) eye chart) in patients with wet AMD. Lucentis showed a difference in mean change in visual acuity of 18 letters for patients treated with 0.3 mg of Lucentis and 21 letters for patients treated with 0.5 mg of Lucentis from study entry compared to those treated with PDT at 12 months. In the first year of this two-year study, patients treated with Lucentis gained an average of 8.5 letters in the 0.3 mg dose group and 11 letters in the 0.5 mg dose group compared to patients treated with PDT, who lost an average of 9.5 letters. Both doses of Lucentis used met the primary endpoint vs. Visudyne photodynamic therapy (p <0.0001). About 94% and 96% of patients taking 0.3 and 0.5 mg intravitreal once-monthly Lucentis, respectively, maintained or improved vision vs. 64% of patients taking Visudyne every three months. Also, Lucentis significantly improved mean change in visual acuity from baseline to 1 year, while Visudyne patients showed a decline. Final results from ANCHOR were published in the Oct. 4, 2006 New England Journal of Medicine.
In June 2006,preliminary data were reported from the double-blind Phase IIIb PIER trial in 184 patients. Lucentis met the primary endpoint. At month 12, patients treated with 0.3 and 0.5 mg Lucentis lost 1.6 and 0.2 letters in visual acuity from baseline, respectively, vs. 16.3 letters in the sham group (p ≤0.0001). Patients received once-monthly injections for the first 3 months followed by once every 3 months, for a total of 24 months. At month three, patients in the 0.3 and 0.5 mg Lucentis groups gained 2.9 and 4.3 letters vs. a loss of 8.7 letters in the sham group. Lucentis provided an initial increase in vision from baseline with monthly dosing and returned to baseline with quarterly treatments. About 83% and 90% of patients injected with 0.3 and 0.5 mg Lucentis, respectively, lost <15 letters in visual acuity at 1 year from baseline vs. 49% of patients in the control group. Improvement of vision by a gain of ≥15 letters was seen in 12% and 13% of the 0.3 and 0.5 Lucentis groups vs. 10% with sham.
Preliminary two-year results announced in March 2006 from the Phase III MARINA study showed that the improvement in the Lucentis groups at year one was maintained at year two as measured by visual acuity endpoints, while there was further deterioration of vision among patients in the control group. The difference between mean visual acuity in the Lucentis arms and the control arm increased at year two compared to year one. At least 90% of patients treated with Lucentis maintained (defined as a loss of less than 15 letters in visual acuity) or improved (defined as a gain of more than 15 letters in visual acuity) vision compared to ~53% of those treated in the control arm at year two [p <0.0001]. Consistent with year-one safety findings, common side effects that occurred more frequently in the Lucentis groups than in the control group at year two were mild to moderate and included conjunctival hemorrhage, increased intraocular pressure, and vitreous floaters. Serious ocular adverse events in the MARINA study that occurred more frequently in the Lucentis-treated arms were uncommon and included endophthalmitis (cumulative 1.3% or less over two years) and intraocular inflammation (cumulative 1.7% or less over two years). Among non-ocular serious adverse events, the cumulative rate of cerebral vascular events and myocardial infarctions at two years was 3% (7/236) in the sham injection group, 4.6% (11/238) in the 0.3 mg Lucentis group and 4.2% (10/239) in the 0.5 mg group. Final results from MARINA were published in the Oct. 4, 2006, edition of the New England Journal of Medicine.
In Oct. 2006, the National Eye Institute (NEI), National Institutes of Health (NIH), funded a clinical trial to compare Lucentis and Avastin for treatment of advanced age-related macular degeneration (AMD). The results from this trial may eventually be used to support off-label use of Avastin for AMD.
In Nov. 2005, Genentech initiated the one year, open-label, U.S. Phase IIIb SAILOR safety study in about 5,000 patients with all subtypes of active subfoveal wet AMD. Patients receive 0.3 or 0.5 mg Lucentis once-monthly for 3 months and thereafter as needed.
In the Dec. 2006 issue of the American Journal of Ophthalmology, researchers from the Wilmer Eye Institute, Johns Hopkins University, reported that Lucentis showed potential for treatment of diabetic retinopathy. Four doses of Lucentis were administered intravitreally over six months into the eyes of ten patients with diabetes already with some vision loss. Within a week, several patients experienced dramatic reductions in the thickness of their maculas, and there were further improvements with each injection. By the end of the study, every patient could read at least two more lines on the standard eye chart, and the thickness of their maculas showed an average 85% decrease.
In Feb. 2008, the National Cancer Institute initiated its head-to-head clinical trial in 1,200 patients to compare the relative safety and effectiveness of Lucentis and Avastin (another angiogenesis inhibitor from Genentech; see the entry above) to treat advanced wet age-related macular degeneration (AMD). As discussed elsewhere in this and the Avastin entry, Avastin is often used off-label for treatment of wet AMD, with Avastin use costing much less for this indication than Lucentis.
The June 2010 approval for retinal vein occlusion (RVA) was largely based on the 397-patient BRAVO and 392-patient CRUISE studies. In the BRAVO trial, the percentage of patients in the Lucentis 0.5 mg study arm who gained 15 or more letters in best-corrected visual acuity (BCVA) from baseline at month six was 61% compared with 29% in the sham injection arm. In the CRUISE study, the percentage of patients on Lucentis 0.5mg study arm who gained 15 or more letters in BCVA after six months was 48% compared with 17% in the sham arm..
In the Oct. 1, 2010 issue of Eye, results were published from a head-to-head comparison trial of Lucentis and Avastin in 22 patients with wet age-related macular degeneration indicating the two are comparably effective. The only significant difference between the two groups was that Avastin patients required eight injections over the year, while Lucentis patients required only four.
In April 2012, results were published in the journal Ophthalmology from the head-to-head trial CATT(Comparison of Age-related macular degeneration Treatment Trials) sponsored by NEI/NIH at years comparing intravitreal Avastin and Lucentis for wet AMD treatment, an indication for which repackaged Avastin is often used off-label. The trial concluded that the two products were comparable in efficacy. However, there was overall significantly higher risk of serious systemic adverse events with intravitrealunlicensed bevacizumab versus Lucentis (p=0.004).
In support of its 2012 diabetic macular edema (DME) approval, safety and effectiveness to treat DME were established in two clinical studies involving 759 patients who were treated and followed for three years. Patients were randomly assigned to receive monthly injections of Lucentis at 0.3 milligrams (mg) or 0.5 mg, or no injections during the first 24 months of the studies. After 24 months, all patients received monthly Lucentis either at 0.3 mg or 0.5 mg. The studies measured the number of patients who gained vision, as measured on an eye chart. Results showed that between 34 percent and 45 percent of those treated with monthly Lucentis 0.3 mg gained at least three lines of vision compared with 12 percent to 18 percent of those who did not receive an injection. No additional benefit was observed with the higher monthly Lucentis dose of 0.5 mg.
In Aug. 2012, an article in the British Medical Journal reported that Avastin was just as effective for treatment of diabetic macular edema as Lucentis. This was expected to increase use of cheaper Avastis for this indication, much as it is used for AMD treatment. The study concluded, " “is no difference in effectiveness between bevacizumab and ranibizumab." The study’s authors looked at studies of the two drugs on Medline, Embase and Cochrane between 1996 and 2011, and analysed the efficacy of both treatments separately. However, head-to-head study between the two agents would need to be conducted to show that one was superior to the other. In Aug. 2012, such a trial was underway at the Medical University of Vienna.
Medical: Lucentis 0.5 mg (0.05 mL) is recommended to be administered by intravitreal (into the fluid of the eye) injection once a month. Although less effective, treatment may be reduced to one injection every three months after the first four injections, if monthly injections are not feasible. Quarterly dosing would give Lucentis a convenience advantage over Macugen (pegaptanib; see related entry), which is dosed every six weeks.
Labeling for Lucentis includes warnings advising of a risk of endophthalmitis and retinal detachments associated with intravitreal injections, as well as a risk of increased intraocular pressure and thromboembolic events. In the days following administration, patients are at risk of developing endophthalmitis. If the eye becomes red, sensitive to light, painful, or develops a change in vision, the patient should seek immediate medical care.
Market: Worldwide revenue was $2.344 billion in 2009; $1.761 billion in 2008; and $1.362 billion in 2007. Total 2006 worldwide sales reported by Roche were CHF 478 million (~$392 million at 7/7/2007 exchange rate). Total U.S. 2006 sales were $380 million. This was incredibly well for a newly-launched product. Total sales reported by Genentech were $815 million in 2007 and $380 million in 2006.
Ex-U.S. sales by Novartis were $1.12 billion in 2009, and about $780 million in 2008.
The 2007 Average Wholesale Price (AWP) is $2,437.50/vial (Red Book, 2007). The wholesale acquisition cost set by Genentech upon approval was $1,950 per vial.
Most patients receive 5-7 injections annually, costing $12,188-$17.0630 at the 2007 AWP. Genentech asserts that out-of-pocket cost per treatment for the typical patient on Medicare or with private insurance is $50 [although many people on private insurance lack such coverage, e.g., pay a percentage of pharmaceutical costs annually up to a set deductable, which can be thousands of dollars; while those with no insurance and low income may be eligible for free product through company-sponsored programs].
Genentech has set up the “Lucentis Made Simple” program to provide Lucentis free to qualified uninsured patients. For comparison, Macugen carries a list price of $995/injection, with its six-week dosing bringing its annual cost on a list price basis to $7,960, but Lucentis is much more effective than Macugen.
As discussed in the entry above concerning Avastin, an earlier VEGF monoclonal antibody from Genentech, there is concern that off-label use of Avastin, which anecdoatally appears effective for wet AMD (see the Avastin entry), will cannibalize sales of Lucentis. With Avastin injections for AMD just costing >$20, or about 1% of the cost of Lucentis, Avastin off-label use may cut into sales of Lucentis (and also Macugen; see related entry). This appears to be a new issue and quandary for the medical community and health care system, where another product from the same company, is apparently safe and effective but costs much less and is not appproved for its particular indication. Physicians and clinics treating AMD may be forced to use Lucentis, or face potential malpractice and liability suits, if patients have adverse reactions to Avastin. Upon approval, Genentech reported it would not block off-label use of Avastin, but what this exactly involves remains to be seen.
In Feb. 2005, SG Cowan analysts projected peak annual sales of up to $600 million, reducing this from $1.1 billion due to projected increased competition from Avastin. Upon approval, RBC Capital Markets estimated Lucentis sales of $146 million in 2006 and $420 million in 2007; and CIBC World Markets estimated annual sales would likely exceed $900 million by 2010.
In Dec. 2007, the National Institute for Health and Clinical Excellence (NICE), U.K., published a draft ruling concerning use of Lucentis (by the National Health Service). This again rejected use of Macugen for wet AMD, and recommended the use of Lucentis by the NHS for the “first eye to come to clinical attention,” abandoning its earlier stance that two eyes had to be effected before Lucentis treatment could start..
In April 2008, the National Institute for Health and Clinical Excellence (NICE), U.K., published a Final Appraisal Document recommending use for wet AMD and the cost-benefits of Lucentis (by the National Health Service). So, NHS now regularly uses or reimburses for Lucentis use. NICE agreed to a new ground-breaking dose-capping scheme, with the NHS paying for a maximum of 14 injections of Lucentis (which should be effective in most cases); and the manufacturer, Novartis, reimburses the cost if the patients needs any more. The two-year cost of Lucentis is about £10,700, assuming eight injections in the first year and six in the second, and about £18,300 if 12 injections are given in the first year and another 12 second, as per the clinical trial regimen.
llustrating the price differences between Avastin and Lucentis, Medicare paid for 480,000 Avastin eye-treatment injections in 2008, compared with 337,000 injections of Lucentis. But the government-funded program spent only $20 million for the Avastin treatments, versus $537 million for Lucentis.
In Oct. 2009, CMS introduced a new J code specifically for Avastin as an ophthalmic therapeutic. This provides a Medicare reimbursement of about $7.20 for a dose of Avastin wet AMD, compared to the $2,000 per-injection price for Lucentis. But this amount is less than the cost of Avastin for an eye-sized diluted dose, which is about $30 to $50 per injection. Thus, this will likely lead to increased use of Lucentis for wet AMD indications:, since physicians/clinics must purchase Avastin themselves, and will lose money if they use diluted Avastin for wet AMD. In contrast, full reimbursement is provided to physicians/clinica for Lucentis. But patients also must pay more, with the 20% co-pay for Lucentis usually about $400.
In late 2010, to boost sales, Genentech began offering ophthalmologists tens of thousands of dollars' worth of confidential rebates every quarter if they use increasing amounts of Lucentis. The aim is to woo docs to Lucentis, which costs $2,000 per dose, and away off-label Avastin.
In March 2011, the National Institute for Health and Clinical Excellence (NICE), U.K., recommended against the NHS using Lucentis for the treatment of diabetic macular oedema (DMO). The evaluating Committee concluded that Novartis' model underestimated the incremental cost-effectiveness ratio (ICER) for Lucentis monotherapy compared with laser photocoagulation, which uses heat to seal ocular blood vessels and is the current standard treatment for people with DMO.
In July 2011, it was reported that Lucentis has become the single biggest line item in the Part B pharmaceutical budget of the Centers for Medicare & Medicaid Services (CMS).
In Oct. 2011, Swiss health authorities used old-fashioned arm-twisting to persuade Novartis to cut its price on the Lucentis eye drug by upwards of 30%. The choice for Roche/Novartis was either a forced approval for Avastin in AMD or a price cut for Lucentis.
In Nov. 2011, the National Institute for Health and Clinical Excellence (NICE), U.K., recommended against the NHS using Lucentis for the treatment of visual impairment caused by macular oedema secondary to central or branch retinal vein occlusion (RVO).
In April 2013, the National Institute for Health and Care Excellence (NICE) issued final draft guidance recommending Lucentis as a treatment for sight problems caused by macular edema, provided Novartis makes the drug available under an agreed patient access scheme (PAS). The draft guidance recommends Lucentis as an option for treating macular oedema following central retinal vein occlusion (CRVO). It also recommends it as a treatment option following branch retinal vein occlusion (BRVO) when standard treatment with laser photocoagulation has not worked, or when it is not suitable because of the extent of macular hemorrhage. The draft guidance follows consideration of further evidence and a PAS submitted by the firm, as well as the results of further work done by the NICE Decision Support Unit.
In late 2011, with the approval of Eylea, Lucentis had about 40% market share for wet AMD treatment, with off-label Avastin having about 60%.
In Aug, 2013, BioTrends reported Eylea's patient share at 26% of surveyed doctors' wet-AMD patients, with this outpacing Lucentis, with about 21% of the surveyed doctors' wet-AMD patients. That means Eylea has overtaken the older Lucentis just two years after approval, despite Roche's having five years to establish Lucentis. Other than price, Eylea is generally considered more convenient for patients, requiring fewer injections for the first two years of wet-AMD treatment, giving it a dosing advantage over both Lucentis and off-label Avastin.
In later 2013, Regeneron plans on filing an NDA for diabetic macular edema (DME), Lucentis and Eyelea will then compete directly for this indication.
Companies involvement:
Full monograph
276 VEGF Mab Fab, rDNA
Nomenclature:
VEGF Mab Fab, rDNA [BIO]
Lucentis [TR]
ranibizumab [USAN]
immunoglobulin G1, anti-(human vascular endothelial growth factor) Fab fragment (human-mouse monoclonal rhuFAB V2 g1-chain), disulfide with human-mouse monoclonal rhuFAB V2 light chain [CAS]
347396-82-1 [CAS RN]
rhuFabV2 [SY]
vascular endothelial growth factor monoclonal antibody Fab fragment, recombinant [SY]
NDC 50242-080-01, [NDC]
molecular weight (kDa) = 48
FDA Class: BLA biologic
Year of approval (FDA) = 2006
Date of 1st FDA approval = 20060630
(in format YYYYMMDD)
Biosimilars/biobetters-related U.S. Patents: | 2019 (based on 7,169,901 reported by Genentech).
US 6,884,879 expires in 2017
2018 based on Cabilly III Tech. Catalysts Intl. (affliliated with Harvest Moon Pharm.) has reported 2011-2017
An analysis by Ohly and Patel cited 2018 (which could be referring to Cabilly III)
|
U.S. Patent Expiration Year: | 2017 |
U.S. Biosimilars Data Exclusivity Expiration: | 2018 |
U.S. Biosimilars Orphan Exclusivity Expiration: | 2013 |
U.S. Biosimilars Launchability Year: | 2019 |
U.S. Biobetters Launchability Year: | 2019 |
Biosimilars/biobetters-related EU Patents: | 2018 (based on EP 0971959; EP 0973804; EP 1787999; and EP 1325932)
Tech. Catalysts Intl. (affliliated with Harvest Moon Pharm.) has reported 2016 - 2018 |
EU Patent Expiration Year: | 2018 |
EU Biosimilars Data Exclusivity Expiration: | 2010 |
EU Biosimilars Orphan Exclusivity Expiration: | 2010 |
EU Biosimilars Launchability Year: | 2018 |
EU Biobetters Launchability Year: | 2018 |
Index Terms:
antibodies (see also immune globulins; monoclonal antibodies)
biopharmaceutical products
monoclonal antibodies, recombinant
monoclonal antibodies, recombnant, humanized
recombinant DNA
varicella-zoster virus strain Oka/Merck
histidine
polysorbate 20 (Tween 20)
tetracycline
trehalose dihydrate
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
priority review status
EU200 Currently Approved in EU
UM001 Marketed Product in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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