Ranibizumab

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Ranibizumab ?
Monoclonal antibody
Type Fab fragment
Source Humanized (from mouse)
Target VEGF-A
Clinical data
Trade names Lucentis
AHFS/Drugs.com monograph
MedlinePlus a607044
Licence data EMA:Link, US FDA:link
Pregnancy cat. C (US)
Legal status POM (UK) -only (US)
Routes Intravitreal injection
Pharmacokinetic data
Half-life Approx. 9 days[1]
Identifiers
CAS number 347396-82-1 YesY
ATC code S01LA04
DrugBank DB01270
UNII ZL1R02VT79 YesY
KEGG D05697 N
ChEMBL CHEMBL1201825 N
Chemical data
Formula C2158H3282N562O681S12 
Mol. mass 48,350 g/mol
 N (what is this?)  (verify)

Ranibizumab (trade name Lucentis) is a monoclonal antibody fragment (Fab) derived from the same parent mouse antibody as bevacizumab (Avastin). It is much smaller than the parent molecule and has been affinity matured to provide stronger binding to VEGF-A. It is an anti-angiogenic that has been approved to treat the "wet" type of age-related macular degeneration (AMD, also ARMD), a common form of age-related vision loss.

Ranibizumab sells for a significantly higher price when compared to bevacizumab.[2] Clinical trials have shown both to be equally effective; however there were some reports of infection after dividing bevacizumab into smaller doses.[3][4]

Ranibizumab was developed by Genentech and is marketed in the United States by Genentech and elsewhere by Novartis,[5] under the brand name Lucentis.


By blocking VEGF-A in the eye, ranibizumab may prevent and reverse vision loss caused by wet macular degeneration.

Administration[edit]

The drug is injected intravitreally (into the vitreous humour of the eye) once a month. If monthly injections are not feasible, the regimen may be reduced to 1 injection every 3 months after the first 4 months.[1]

Dosing every 3 months is linked to a loss of approximately 5 letters (1 line) in visual acuity for the following 9 months as compared with dosing on a monthly basis. Large phase 3 clinical trials (MARINA and ANCHOR) which randomized patients with wet macular degeneration showed that 95% of ranibizumab-treated patients maintained visual acuity compared with 62% of those administered placebo (P < .01) at 1 year; moreover, up to 40% demonstrated an improvement in vision of at least 3 lines. Vision maintenance and loss were defined as a loss of less than 15 letters and a gain of 15 or more letters in visual acuity, respectively, as measured using the Early Treatment of Diabetic Retinopathy eye chart.[6]

Side effects[edit]

The most common side effects in clinical trials were conjunctival hemorrhage, eye pain, vitreous floaters, increased intraocular pressure, and intraocular inflammation.

Although there is a theoretical risk for arterial thromboembolic events in patients receiving VEGF-inhibitors by intravitreal injection, the observed incidence rate was low (< 4%) and similar to that seen in patients randomized to placebo.

Serious adverse events related to the injection procedure occurred with an incidence rate of less than 1% and included endophthalmitis, retinal detachment, and traumatic cataracts. Other serious ocular adverse events observed among ranibizumab-treated patients (incidence rate < 1%) included intraocular inflammation and blindness.[7]

Interactions[edit]

No significant interactions are known. [8]

Comparison to Bevacizumab and Marketing Issues[edit]

On November 3, 2010, The New York Times reported that Genentech began offering secret rebates to about 300 ophthalmologists in an apparent inducement to get them to use more ranibizumab rather than their less expensive bevacizumab. This may have been in anticipation of the results of the CATT clinical trial,[9] which was sponsored by the National Eye Institute, and compared the relative safety and efficacy of ranibizumab and bevacizumab in treating AMD. In 2008, bevacizumab cost Medicare only $20 million for about 480,000 injections, while ranibizumab cost Medicare $537 million for only 337,000 injections.[10] A small study showed no superior effect of ranibizumab versus bevacizumab in direct comparison.[11] The CATT trial data was published in the New England Journal of Medicine in May 2011. The trial showed that the two drugs "had equivalent effects on visual acuity when administered according to the same schedule". Serious adverse events were more common in the bevacizumab arm of the trial. These were of a diverse range of types, and not of types that had previously been considered of concern. Similarly, a 2012 meta analysis by the Cochrane Group concluded that treatment with bevacizumab is associated with a 2.8 fold greater risk of ocular adverse events and a 1.3 fold greater risk of serious infections and gastrointestinal disorders relative to ranibizumab.[12][9]

References[edit]

  1. ^ a b Lucentis Prescribing Information. Genentech. June 2010.
  2. ^ Peter Whoriskey and Dan Keating (December 7, 2013). "An effective eye drug is available for $50. But many doctors choose a $2,000 alternative.". The Washington Post. 
  3. ^ Alicia Mundy (June 17, 2010). "Medicare Eye Study Finds Untapped Savings". The Wall Street Journal. 
  4. ^ Tufail, A.; Patel, P. J.; Egan, C.; Hykin, P.; Da Cruz, L.; Gregor, Z.; Dowler, J.; Majid, M. A.; Bailey, C.; Mohamed, Q.; Johnston, R.; Bunce, C.; Xing, W. (2010). "Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study". BMJ 340: c2459–c2459. doi:10.1136/bmj.c2459. 
  5. ^ Lucentis Fact Sheet. Genentech.
  6. ^ Lai, T. Y. Y.; Lai, T. Y. (2013). "Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema". Clinical Interventions in Aging 8: 467–483. doi:10.2147/CIA.S36811. PMC 3677930. PMID 23766636.  edit
  7. ^ Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X. [page needed]
  8. ^ Ranibizumab, Lexi-Drugs. Ranibizumab. Lexi-Comp, Inc; 2007.
  9. ^ a b Catt Research, Group; Martin, DF; Maguire, MG; Ying, GS; Grunwald, JE; Fine, SL; Jaffe, GJ (2011). "Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration". New England Journal of Medicine 364 (20): 1897–1908. doi:10.1056/NEJMoa1102673. PMC 3157322. PMID 21526923. 
  10. ^ Andrew Pollack (November 3, 2010). "Genentech Offers Secret Rebates for Eye Drug". The New York Times. 
  11. ^ Subramanian, M L; Abedi, G; Ness, S; Ahmed, E; Fenberg, M; Daly, M K; Houranieh, A; Feinberg, E B (2010). "Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomised clinical trial". Eye 24 (11): 1708–1715. doi:10.1038/eye.2010.147. PMID 20885427. 
  12. ^ Schmucker C, Ehlken C, Agostini HT, et al. (2012). "A safety review and meta-analyses of bevacizumab and ranibizumab: off-label versus goldstandard". PLoS ONE 7 (8): e42701. doi:10.1371/journal.pone.0042701. PMC 3411814. PMID 22880086. 

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