Intravitreal injections of Bevacizumab and/or ranibizumab are most commonly used as angiogenesis inhibitors for age-related macular degeneration, diabetic retinopathy, and several vascular disorders of ophthalmology particularly retinal diseases. Currently, the only available method to administer these drugs i.e Bevacizumab or ranibizumab is by repeated injections into the vitreous cavity every few months, due to short lasting effects. This long lasting procedure adds an extra financial burden to patients and their families. Why have pharmacology researchers and/or drug industries not succeeded in producing bevacizumab or ranibizumab with slow sustained release i.e an implant or liposomal encapsulated delivery system?
Not sure of the biochemistry, but the emphasis currently seems to be on sustained delivery devices like various types of implants rather than drug modification
Sorry, I just saw the last line of your question. There are many implant variations in development and trials designed to reduce the need for monthly injections.
Dear Jefferey, I agree with you that there are many implants variation in developement and trail designs to reduce the need for monthly injection. The example of the implant is such as Dexamethasone implant (Ozurdex). Why not implant or slow sustained delivery for Bevacizumab and/or ranibizumab ?
sustained delivery of ranibizumab is under consideration. It is very unlikely that any one will develop similar device for bevacizumab given that this medication does not have market authorisation for intraocular use in any jurisdiction.
Thanks Simon Kelly. Sustained release delivery of ranizumab will help to reduce repeated use. Bavacizumab is much more commonly used for intraocular use in Asian countries and India even if this medication does not have market authorization due to relatively lower cost compared to ranizumab. Research should consider making its slow sustained release delivery which will help large number of patients .
But why would any pharma company undertake such research if they can not sell the product?
But no pharma company will be able to sell such a product in any developed nation.
Jagat, what we are saying is that big pharmaceutical companies are not motivated to work on Avastin slow release methods because it's not good for them financially (even though it may be good for some patients and state healthcare expenditure). Simple as that. Lucentis is a different story of course. Any method developed for Lucentis however may be useable with Avastin as well (since these reservoirs may still need to be replenished from the outside from time to time, requiring the ophthalmologists to "fill up the tank" with Lucentis periodically. I imagine, they will have no problem "filling up with the cheaper gas"... unless of course the release rate will be very different for the two drugs (if I was "the" company, I'd make sure that was the case).
The real question to me here, is whether it would be really beneficial for patients to have their VEGF cleared out that much. I've just been at a superb presentation by Patricia D'Amore from Schepens and I came away with a renewed worry about anti-VEGF therapy. It turns out (not too surprisingly) that VEGF production in the normal retina may be required to preserve photoreceptor and Muller cells. Take that out really well and fully and you may end up with something resembling geographic atrophy. So although continual release from an artificial lens or some other device may reduce costs and problems associated with repeated injections, but the doses (ie speed of release) used will have to be titrated very carefully to avoid problems in he retina (as well as the anterior part of the eye). That may take a few years.
I agree with Peter Barabas that big pharmaceutical company will not be able to sell slow- stained released Avastine etc as there is no financial benefit for the pharma company but it is wrong on the part of pharma company ignoring the interest of out millions of suffering patients.
Dr.Barabas, do you have some good references regarding this potential side effect of lucentis.
There are few such papers (not very surprising, since it's harder to publish negative papers), though I must admit, I did not spend a whole lot of time, reading into this subject area. This paper is the basis of the presentation that I've seen:
http://www.ncbi.nlm.nih.gov/pubmed/18978936
The model animal used here was mouse, thus how far this can be extended to the situation in humans - i don't know. After working a few years with different mouse models of human diseases, I'm very cautious but it just seems logical, that VEGF may be generally (across different species) an important survival factor for Muller cells.
usually if we will able to use long lasting anti VEGF iv drugs, we need to take in account beneficial effect for the macula but also for a long lasting effect on the VEGF on retinal cells and on hearth and other cerebro vascular structures. So that if we need to suspend the treatment the effect lasts for only 4 weeks istead 3-6-12 months
I invite you to read my review paper on Avastin and LUCENTIS in retinal vein occlusion. incorporated into my RESEARCH GATE site. I think that patients sufferring from AMD, RVO, DR represent the same elder population that is why systemic and ocular effects and tachyphylasis problem will be the same. Besides, the latest published findings confirm that cheaper Avastin is not so safe as Lucentis
Avastin: Therapeutic Potential in Vascular Retinopathy due to Retinal Vein Occlusion
Lucentis , etc
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