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Posts tagged ‘Ophthalmology market’

The FDA earlier this week issued a safety alert to doctors that repackaged bevacizumab (Avastin®) had caused serious eye infections in 12 patients in Florida. The New York Times today reports that five patients at the Veterans Affairs Medical Center in Los Angeles have gone blind as a result of an eye infection following injection of compounded Avastin.

I have written previously about the Lucentis v Avastin debate and the results in the Comparison of Age-related macular degeneration treatment trial (CATT) published earlier this year in the New England Journal of Medicine.

It is not good news that contamination has occurred while compounding bevacizumab (Avastin) from sterile100mg/4mL single use preservative-free vials into individual 1mL syringes.

Genentech/Roche may see this news as reinforcing their position that ranibizumab (Lucentis®) should only be used, since it comes in the correct dose for injection in the eye. However, this ignores the reality caused by the fact that Lucentis is approximately 40x the cost of compounded Avastin ($1950 versus $50).

This week’s news does not support the proposition that intravitreal injection of bevacizumab is not safe and effective for the treatment of AMD, nor any suggestion that pharmacies properly accredited and experienced in aseptic techniques are not qualified to do this. Pharmacists compound drugs everyday.

As the FDA notes in their alert:

“Health care professionals should be aware that repackaging sterile drugs without proper aseptic technique can compromise product sterility, potentially putting the patient at risk for microbial infections.  Health care professionals should ensure that drug products are obtained from appropriate, reliable sources and properly administered.”

However, there is no evidence to suggest that the pharmacies who undertook the Avastin compounding that led to the infection were not “appropriate, reliable sources and properly administered.”

The New York Times notes that the the contaminated Avastin came from the pharmacy at the main campus of the V.A. Greater Los Angeles Healthcare System.  There is no mention of whether the VA pharmacists did the compounding themselves or sourced the drug elsewhere.

According to a news report in the Florida SunSentinel, the pharmacy identified as the source of the infection in Florida is InfuPharma. This is not a retail pharmacist in the high street, but a specialist compounding pharmacy that advertises sterile preparations for numerous products. Licensed pharmacists run this specialist company and looking at their website they do appear to be experienced in this area.

Endophthalmitis is a serious eye infection that may lead to loss of vision. The contamination should not have occurred.  These incidents should not, however, be blown out of proportion in the Lucentis v. Avastin debate.

Sadly, infections and contamination happen in hospitals and the healthcare industry all the time. Even the FDA approved manufacturing facilities of pharmaceutical companies have experienced problems in recent years.  Last summer, BMS experienced issues with sterile manufacturing standards at their Puerto Rico plant following FDA inspections.  Earlier this week, Baxter announced they had filed a lawsuit against Teva for indemnification over a hepatitis C outbreak following reuse of oversize propofol vials.

The news of serious eye infections with repackaged Avastin must, therefore, be put in context. There are countless patients around the world who have benefited from intravitreal injections of Avastin for treatment of their age-related macular degeneration (AMD). The issue raised by the infections in Florida and Los Angeles is whether there is adequate inspection and certification of compounding pharmacies, and whether there is a need for more State regulation and inspections in this area.

Disclosure:  I have written freelance articles for Pharmacy Today, the magazine of the American Pharmacists Association.

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There is a lot of buzz this week about Lucentis versus Avastin for the treatment of wet age-related macular degeneration (AMD), something that will be talked about in more detail at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting this weekend in Fort Lauderdale.

Also on the radar at ARVO is more news from Second Sight and their Argus II Retinal Prosthesis (something that I have previously written about on this blog).  For those interested there is a press conference at ARVO on Tuesday, May 3 from 5-6pm.

Second Sight presents updated results from the Argus II Retinal Prosthesis clinical trial, including sentence reading and color vision restoration for previously blind subjects. Two trial participants and independent investigators from the trial will be available for interviews.

Which brings me back to a Nature article published earlier this month that I have been meaning to write about showing, for the first time, the ability to generate a three-dimensional culture of neural retinal tissue from mouse embryonic stem (ES) cells.  A word of warning, you may find the paper a little tough to follow unless you are a scientist in this field.

Eiraku and colleagues from Japan were able to culture retinal tissue similar to that seen in the human eye.  Eye formation starts as an optical vesicle that then develops into a two-walled optic cup.  As the authors note “optic cup development occurs in a complex environment affected by neighbouring tissues.”

What the authors showed in their research was the ability to culture retinal tissue containing ganglion cells, photoreceptors and bipolar cells.  They conclude:

Collectively, these findings demonstrate that the fully stratified neutral retina tissue architecture in this ES-cell culture self-forms in a spatiotemporally regulated manner mimicking in-vivo development.

My take on this research is that it is an important milestone in regenerative medicine that could lead to the prospect of retinal transplants in the future.  I look forward to learning more at ARVO about what the future may hold for retinal transplants derived from human stem cells.

ResearchBlogging.orgEiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., & Sasai, Y. (2011). Self-organizing optic-cup morphogenesis in three-dimensional culture Nature, 472 (7341), 51-56 DOI: 10.1038/nature09941

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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