Avastin problem: cause for concern
Four patients of the Moka Eye Hospital recently lost their vision, a dramatic problem they relate to Avastin injection. An investigation committee has been set up to look into the problem. We here intend to bring scientific information to the committee and to the public in general for a more informed understanding and analysis of the problem.
Avastin - anti-VEGF for cancer treatment
Avastin (brand name) or bevacizumab (generic biologics drug name) is a monoclonal antibody developed by Genentech Co. and approved by FDA in 2004 for the treatment of colorectal cancer and further extended to brain tumour, lung cancer and metastasis breast cancer treatment. Its approval in the latter case was withdrawn in 2011. Tumors release Vascular Endothelial Growth Factor (VEGF) protein which promotes angiogenesis (new blood vessel growth) and in turn feed the growth of the tumor. Avastin acts as an inhibitor to angiogenesis by binding to VEGF. We became interested in this matter at the Centre for Biomedical and Biomaterials Research (CBBR) as one of our mainstream research interest is to develop nanocarriers for more efficient delivery of anti-cancer drugs.
Avastin - treatment of eye diseases
In 2008, FDA authorized the off-label use of Avastin for eye diseases including wet form of age-related macular degeneration (neovascular AMD) and diabetic retinopathy. Both lead to loss of vision and blindness. Patients with AMD have elevated levels of VEGF which cause abnormal blood vessel growth behind the retina and leakage of fluids, leading to vision loss. Similarly to cancer, Avastin treats “wet” macular degeneration here also by blocking VEGF. Avastin is injected directly into the eye (intravitreal injection). Several studies have reported on the safe use of Avastin for AMD treatment. However, reports around the world including the USA, Germany and China highlight cases of endophthalmitis (severe inflammation of the eye) and blindness following intravitreal injection of Avastin. It appears that infections is the main cause of blindness.
Avastin injection and cases of endolphthalmitis (severe inflammation of the eye)
Goldberg et al. (Am J Ophthalmol. 2012, 153(2):204-208) reported twelve patients with Streptococcus endophthalmitis after injection with intravitreal bevacizumab prepared by the same compounding pharmacy. They concluded that the most likely cause of this infection was contamination during syringe preparation by the compounding pharmacy. In an article entitled ‘Avastin doesn't blind people, people blind people’ by Gonzalez et al. (Am J Ophthalmol. 2012, 153(2):196-203), the authors concluded that cases of vision loss occurring after the intravitreal injection of bevacizumab is not the result of the drug or the injection technique, but rather of the compounding procedures used to prepare the syringes containing the bevacizumab. They recommended that preparation and handling guidelines as prescribed by the United States Pharmacopoeia Chapter 797 should be strictly adhered to in order to prevent microbial contamination. For instance, the same vial of drug can be avoided by using a single vial of bevacizumab for each eye. FDA warned about the risks of contamination when repackaging Avastin.
It is possible that infections may have caused blindness of Mauritian patients too. To shed more light into the cause(s) of vision loss, it is important to examine the origin of the Avastin (whether re-packaged or not) and lot number as well as the storage and handling of the injection vials to identify pre- or post- infection risks. Information has also to be made available to patients on risks of infection so that they can benefit from early antibiotic treatment. We don’t intend to blame anybody or any institution but help examine the root cause of the problem where researchers and healthcare professionals could work closely together.