Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Vision’

Due to the pressure of other commitments, I only had the pleasure of attending the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) for two days, but one of my key take home messages from the meeting is how we can use the eye as a window into the brain.  This is particularly relevant to Alzheimer’s research.

ARVO researchers at a lunchtime workshop that I attended asked the question of what can we learn from shared disease mechanisms in age-related macular degeneration (AMD), Alzheimer’s Disease (AD) and Glaucoma to devise therapies of the future?

What I learnt in the introduction by Nicholas Bazan from LSU Health Sciences is that both AD and AMD are both multifactorial, genetically complex, progressive, late-onset neurodegenerative conditions.  Common features include:

  1. Age-related neurodegeneration
  2. Amyloid precursor protein mis-processing
  3. Non-resolving inflammatory response
  4. Selective apoptotic cell death

Researchers in the workshop presented early experimental findings.

Catherine Bowes Rickman from Duke presented data that showed anti-amyloid immunotherapy blocks retinal pigment epithelium (RPE) damage and visual function defects in an AMD-like mouse model.  Interesting questions were raised as to whether mouse Aß aggregates differently to human, so is this a good model?

Adriana Di Polo from the University of Montreal discussed Glaucoma and AD: common neurodegenerative pathways and therapeutic targets. It was interesting to note that high rates of visual abnormalities, including glaucoma, have been reported in AD patients, but causality has not been established. Neuronal loss in both glaucoma and alzheimer’s disease occurs via common cell death processes including altered metabolism of Amyloid Precursor Protein (APP) and Aß.

What Di Polo highlighted in her talk was the potential to use therapies effective in one disease to treat the other e.g. galantamine is approved for treatment of mild to moderate AD symptoms.  Because it crosses the retinal-brain barrier and has high bioavailability, she presented results using this in an animal model of glaucoma.

Her conclusion was that “therapeutic modalities that promote neuroprotection in AD may be useful in glaucoma and vice versa.”

The third speaker of this fascinating workshop was Ian Trounce from Melbourne, who challenged the Amyloid theory of AD. His hypothesis was that sAPPα may trigger oxidative stress in mitochondria and be the problem. He discussed the increasing acceptance/overlap in pathologies between Parkinson’s and AD.  He presented data that sAPPα overexpression protects retinal ganglion cells (RGC) from rotenone via PI3K-AKT activation.

Critical feedback on the three presentations was provided by Guy Eakin of the American Health Assistance Foundation (AHAF) and Imre Lengyel from UCL.

As Dr Lengyel succinctly notes in his UCL Institute of Ophthalmology bio:

“It appears that the development of age related macular degeneration (AMD) and Alzheimer’s disease (AD) share similar histopathology, vascular risk factors and genetic predisposition. In addition, the development of AMD appears to use similar or identical steps on the cellular and molecular levels to AD: vascular damage, oxidative stress, inflammation, extracellular protein and peptide degradation or deposition, and the role for lipids and trace elements (especially zinc) in the degenerative process are amongst the many common features. Furthermore, amyloid beta peptides are an integral part of drusen (the hallmark lesion in AMD) and their formation might be similar to plaque formation in AD.”

I applaud ARVO for looking at how the eye can be used as a window into the brain. It raises the intriguing prospect that research on AMD may not only help understand the cause of AD, but that the eye may serve as an experimental model for future new treatments. Collaboration between Opthalmology and Alzheimer’s researchers is something I expect and hope we will see more of.


This weekend I will be at the annual meeting of The Association for Research in Vision and Ophthalmology (ARVO) in Fort Lauderdale.

I’m excited about attending because earlier in my career I worked at Alcon Laboratories on European IDE clinical trials for three novel intra-ocular lenses.

ARVO is the ophthalmology equivalent of AACR and is where scientists involved in drug, device research meet to discuss new findings and early stage research.

The title of meeting is “Visionary Genomics.”  After listening to the plenary session at the recent AACR annual meeting by Lynda Chin on how insights from cancer genomics are translating into personalized medicine, I’m looking forward to seeing the impact of genomics on vision research.

Sunday’s ARVO/Alcon keynote presentation is from Roderick McInnes who is the Canada Research Chair in Neurogenetics at McGill University in Montreal.

A presentation that is already generating some advance interest is Sunday’s presentation of the results from the Comparison of Age Related Macular Degeneration Treatments Trials (CATT).

Age related macular degeneration (AMD) is the leading cause of vision loss in those over 65 in the United States, with over 7 million people estimated to be at risk.  Once you have AMD in one eye, you have a 43% risk of developing it in the other eye over a  five year period, a scary statistic!

The first CATT clinical trial is between bevacizumab (Avastin®) and ranibizumab (Lucentis®), both similar anti-VEGF inhibitors that are derived from the same monoclonal antibody.  It will be interesting to see whether the data supports the current practice of off-label use of bevacizumab given its lower cost compared to ranibizumab.

The findings from this data will also potentially impact aflibercept (VEGF-Trap) that is being co-developed by Bayer and Regeneron.  In February, Regeneron submitted a biologics license application (BLA) to the FDA for the use of VEGF-Trap in wet AMD.

The initial results from the aflibercept phase III AMD trial announced late last year showed a non-inferiority to ranibizumab.  If aflibercept is approved and comes to market in 2012, depending on the CATT results, it may have to compete on price against off-label bevacizumab in AMD.  Whether a more convenient injection once every two months for VEGF-Trap (compared to monthly for Lucentis) is sufficient to justify a price premium, it will be interesting to watch the market dynamics in this space.

You can find more about the meeting on the ARVO conference website and they have also put up a blog for the meeting.   The theme of my blog posts over the next few days will be ophthalmology related, and I expect to be live tweeting from ARVO 2011 on Sunday and Monday.  I’ll also be aggregating tweets from the meeting (hashtag #ARVO11) on this blog.


Detecting a door or a window may not be a big deal for all of us with normal vision, but for those who lose their sight, e.g. through retinitis pigmentosa (RP), a new “artificial retina” now provides hope of a better quality of life.

The Argus™ II Retinal Prosthesis System from California based company Second Sight, has just received CE marking.  This innovative device can now be sold and marketed within Europe, but it remains investigational in the United States. It is the first such device to be approved.

While this blog is mainly focused on the biotechnology industry, I’m very interested in innovation and bringing novel products to market. I also have a personal interest in the ophthalmology market.  Earlier in my career, I spent three years at Alcon working with leading European ophthalmologists on intra-ocular lens clinical trials, including the IDE registration trial for AcrySof®.

In the same way that a cochlear implant does not restore hearing, the “artificial retina” or so-called “bionic eye” from Second Sight is not intended to restore vision, instead it artificially provides electrical signals that it is hoped the brain can learn to interpret as shapes.

The “artificial retina” has three parts, a small video camera worn in a pair of glasses that captures visual images.  This transmits the electronic images to a video processing unit worn by the patient.  Data is then transmitted wirelessly to an implant that is located on top of the retina.

The array of electrodes resting on the retina stimulates those rods and cones that remain functional to generate electrical impulses that are then transmitted down the optic nerve to the brain.  Patients learn to interpret the patterns of light that are generated, and in the process gain some sense of visual perception that improves their daily life.

In an interview broadcast on French radio station, RTL one of the four French patients in the clinical trial, Thierry, talks about how this retinal stimulation device has improved his autonomy and quality of life.

When faced with blindness, any progress is noteworthy and it will be interesting to see the extent to which this technology can be further developed.  I expect that more clinical trial data will be forthcoming at the annual meeting of ARVO (Association for Research in Vision and Ophthalmology) in May.

Update August 23, 2012:  FDA Panel to review whether to recommend of approval of Argus II artificial retina in the United States

The FDA Ophthalmic Devices Panel will review on September 28, 2012 the Humanitarian Device Exemption (HDE) market approval application by Second Sight for its Argus II Retinal Prosthesis System with an indication for patients with severe to profound retinitis pigmentosa (RP) who have bare or no light perception in both eyes.

What is a Humanitarian Device Exemption? 

“An HDE is similar in both form and content to a premarket approval (PMA) application, but is exempt from the effectiveness requirements of a PMA. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose. The application, however, must contain sufficient information for FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment.”  U.S. Food & Drug Administration

Given the lower standard required for a HDE, and the fact that Second Sight obtained a CE mark in Europe, it would be hard to believe the FDA advisory panel will not recommend approval in a patient population that are effectively blind.

However, the FDA guidance also notes that an approval of an HDE, while allowing marketing of the device, does require it’s use to be at facilities where an institutional review board (IRB) has approved the use of the device. If approved for sale in the US, the market for Second Sight will be limited as a result to academic and hospital settings that have an IRB able to provide the necessary oversight and review.

“An approved HDE authorizes marketing of the HUD. However, an HUD may only be used in facilities that have established a local institutional review board (IRB) to supervise clinical testing of devices and after an IRB has approved the use of the device to treat or diagnose the specific disease. The labeling for an HUD must state that the device is an humanitarian use device and that, although the device is authorized by Federal Law, the effectiveness of the device for the specific indication has not been demonstrated.”

For those interested in more information, background material on the HDE application will be available on the FDA website no later than 2 days prior to the September 28 meeting of the Ophthalmic Devices Panel of the Medical Devices Advisory Committee.

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