Monday, April 30, 2012

CATT Update 16: Two-year Results Published in Ophthalmology – No Significant Difference Found Between Avastin and Lucentis

For those of you who have been following my writings on Avastin vs. Lucentis and on the CATT Study, the two-year results comparing Avastin to Lucentis have just been published in Ophthalmology (1) and no significant differences between either the two drugs or dosing patterns (once monthly or as needed) has been found.

As illustrated in the graphic below, the results for monthly treatments were slightly better than when injected as needed but, as the study’s authors noted, "Both drugs were highly effective regardless of the approach to dosing. There was slightly less vision gain with as-needed treatment. Patients seeking the small extra advantage of monthly treatment need to be mindful of the additional burden, risks, and costs of monthly injections. Since as-needed dosing required 10 fewer eye injections over the course of two years and yielded similar visual results, many patients may choose this option." said Daniel F. Martin, M.D., study chair for CATT and chairman of the Cole Eye Institute at the Cleveland Clinic.


The study authors concluded, “Ranibizumab (Lucentis) and bevacizumab (Avastin) had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

Furthermore, as the principal investigator stated, "The dramatic and lasting improvement in vision with these two drugs is extraordinary. At two-years, two-thirds of patients had driving vision (20/40 vision or better). With previous treatments, only 15 percent of patients retained similar visual acuity," said Maureen Maguire, Ph.D., principal investigator, CATT Coordinating Center at the University of Pennsylvania.

Here, in its entirety is the news release prepared by the National Eye Institute to accompany the study’s release:

Avastin and Lucentis are equivalent in treating age-related macular degeneration

At two years, Avastin (bevacizumab) and Lucentis (ranibizumab injection), two widely used drugs to treat age-related macular degeneration (AMD), improve vision when  administered monthly or on an as needed basis, although greater improvements in vision were seen with monthly administration for this common, debilitating eye disease, according to researchers supported by the National Institutes of Health.

Of the two drugs, Avastin is most frequently used to treat AMD. However, prior to the Comparison of AMD Treatments Trials (CATT), a two-year clinical trial, the two drugs had never been compared head-to-head. Second year results were published today in the journal Ophthalmology.  First year results were published in the May 19, 2011 issue of the New England Journal of Medicine.  

AMD is the leading cause of vision loss and blindness in older Americans. In its advanced stages, the wet form of AMD spurs the growth of abnormal blood vessels, which leak fluid and blood into the macula and obscure vision. The macula is the central portion of the retina that allows us to look straight ahead and to perceive fine visual detail. Accumulation of fluid and blood damages the macula, causing loss of central vision, which can severely impede mobility and independence. Without treatment, most patients become unable to drive, read, recognize faces or perform tasks that require hand-eye coordination.

"Therapies for AMD require repeated treatment to prevent vision loss. Results of this clinical trial provide evidence that long-term treatment with either drug results in a robust and lasting improvement in vision. Patients and clinicians now have valuable information to base treatment decisions," said Paul A. Sieving, M.D., Ph.D., director of the NEI.

Avastin and Lucentis block growth of abnormal blood vessels and leakage of fluid from the vessels. Lucentis was approved by the U.S. Food and Drug Administration (FDA) in 2006 for the treatment of AMD.  Avastin is very similar to Lucentis but is not approved by the FDA for this purpose. Avastin is approved for other indications. Most clinicians use these drugs on an as-needed basis when there is evidence of active disease, such as fluid leakage. However, in the original clinical trials for AMD, Lucentis was administered monthly. It was unknown if as-needed dosing would produce the same long-term visual improvements achieved with monthly administration.

Thus, CATT was designed to compare Avastin and Lucentis with monthly and as-needed treatment schedules. At enrollment, patients were assigned to four treatment groups defined by drug (Avastin or Lucentis) and dosing regimen (monthly or as-needed). After year one, patients initially assigned to monthly treatment were randomly reassigned to monthly or as-needed treatment without changing their drug assignment.

At two years, visual acuity with monthly treatment was slightly better than with as-needed dosing, regardless of the drug. As measured on an eye chart, monthly treatment resulted in a mean improvement of about half a line better than as-needed dosing. Switching to as-needed treatment after one year of monthly treatment yielded outcomes nearly equal to those obtained with as-needed treatment for the full two years. Changes in retinal anatomy differed by drug and frequency of treatment, but did not have an impact on vision through two years.

"Both drugs were highly effective regardless of the approach to dosing. There was slightly less vision gain with as-needed treatment. Patients seeking the small extra advantage of monthly treatment need to be mindful of the additional burden, risks, and costs of monthly injections.  Since as-needed dosing required 10 fewer eye injections over the course of two years and yielded similar visual results, many patients may choose this option." said Daniel F. Martin, M.D., study chair for CATT and chairman of the Cole Eye Institute at the Cleveland Clinic.

Adverse events indicate development or worsening of a medical condition. They may or may not be causally associated with the clinical trial treatment, but they are always monitored and reported in any clinical trial. The median age of patients in CATT was over 80 years, and a high rate of hospitalizations would be anticipated as a result of chronic or acute medical conditions more common to older populations.

Serious adverse events (SAEs) occurred at a 40 percent rate for patients receiving Avastin and a 32 percent rate for patients receiving Lucentis. Although Avastin had a higher rate of SAEs, they were distributed across many different conditions, most of which were not associated with Avastin when evaluated in cancer clinical trials, in which the drug was administered at 500 times the dose used for AMD. Fewer doses were associated with a higher rate of SAEs, which is not a typical dose-response relationship. The number of deaths, heart attacks, and strokes were low and similar for both drugs during the study. CATT was not capable of determining whether there is an association between a particular adverse event and treatment. Additional data from other clinical trials may provide information on long-term safety profiles of these drugs when used to treat AMD.

"The dramatic and lasting improvement in vision with these two drugs is extraordinary.  At two-years, two-thirds of patients had driving vision (20/40 vision or better). With previous treatments, only 15 percent of patients retained similar visual acuity," said Maureen Maguire, Ph.D., principal investigator, CATT Coordinating Center at the University of Pennsylvania.


1. Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration: Two-Year Results, Daniel F. Martin, MD, Maureen G. Maguire, PhD, et al, Ophthalmology, April 30, 2012.

Tuesday, April 24, 2012

Iluvien Update 6: First European Marketing Approval Obtained

While U.S. marketing approval appears to be out of reach for Alimera and pSivida for Iluvien for the sustained release treatment of diabetic macular edema, the first of six expected approvals for Europe has been obtained. The companies announced that the Austrian Agency for Health and Food Safety (Österreichische Agentur für Gesundheit und Ernährungssicherheit, AGES) had granted marketing authorization to Iluvien for the treatment of vision impairment associated with chronic diabetic macular edema (DME) considered insufficiently responsive to available therapies.

The Austrian authorization is the first national approval in the EU. Additional Concerned Members States (CMS) marketing authorizations are expected in the coming months.

Here is the pertinent information released from both Alimera and pSivida:


Iluvien Receives Marketing Authorization in Austria for the Treatment of Chronic Diabetic Macular Edema

ATLANTA, April 24, 2012 - Alimera Sciences, Inc., a biopharmaceutical company that specializes in the research, development and commercialization of prescription ophthalmic pharmaceuticals, announced that the Austrian Agency for Health and Food Safety (Österreichische Agentur für Gesundheit und Ernährungssicherheit, AGES) had granted marketing authorization to Iluvien for the treatment of vision impairment associated with chronic diabetic macular edema (DME) considered insufficiently responsive to available therapies.

This marketing authorization follows the completion of the Decentralized Regulatory Procedure (DCP), in which the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom, serving as the Reference Member State, delivered a positive outcome for Iluvien along with six Concerned Members States (CMS), which include Austria, France, Germany, Italy, Spain and Portugal. The Austrian authorization is the first national approval in the EU. Additional CMS marketing authorizations are expected in the coming months.

"We are excited to receive this marketing authorization and pleased that DME patients in Austria will have this therapy available to them. We look forward to receiving the additional expected approvals from the U.K. and other Concerned Member States as we continue on track with our commercialization plans in the EU," said Dan Myers, president and chief executive officer, Alimera Sciences.

The International Diabetes Federation estimates that approximately 750,000 people are currently living with diabetes in Austria, and according to Alimera's estimates, more than 40,000 people suffer from DME.

Iluvien is Alimera's sustained release intravitreal implant that delivers sub-microgram levels of fluocinolone acetonide (FAc) for up to 36 months for the treatment of chronic DME. The clinical trial data showed that in patients with chronic DME at month 30, after receiving the Iluvien implant, 38 percent of patients experienced an improvement from baseline in their best corrected visual acuity on the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart of 15 letters or more. At the completion of the 36-month study, 34 percent had achieved the same result. This effect was highly statistically significant as compared to the sham control group, which received laser and other intravitreally administered therapies.

"With the approval of Iluvien, Austrians who are suffering from chronic diabetic macular edema and unresponsive to current therapies can now be offered another chance to maintain their vision," said Dr. Michael Stur, professor at the Medical University of Vienna. "I believe having this innovative, sustained release drug available to my patients will prove to be beneficial in the long-term management of their condition."

pSivida, which licenses the drug delivery system to Alimera added the following information: "We are very pleased Iluvien has received this marketing authorization and will soon be available to patients in Austria," said Dr. Paul Ashton, president and chief executive officer of pSivida . We look forward to Iluvien receiving the additional expected EU approvals."

Thursday, April 19, 2012

Retinitis Pigmentosa Update: Three Blind Mice – Let There Be Sight!

In a potential breakthrough, especially for those suffering from retinitis pigmentosa who have lost vision due to degenerated photoreceptors in their retina, scientists from the University College of London (UCL) Institute of Ophthalmology have managed to transfer immature (or progenitor) rod-photoreceptor cells – cells that are more developed than stem cells, but not quite mature rod cells – from healthy mice into those suffering from deficiencies in photoreceptors (blind mice) and, after a few weeks, have found that the transplanted cells appeared to be functioning almost as well as normal rod-photoreceptor cells and had formed the connections needed to transmit visual information to the brain.

This is very early work along a long and tedious path to, hopefully, eventual success, but a small step in the right direction. The ultimate goal would be to use embryonic stem cells to grow both rod and cone cells for transplantation into humans suffering from degenerated cone and rod cells.

This potential breakthrough could mean hope for thousands of people with photoreceptor deficiencies (and blindness), because of diseases such as age-related macular degeneration, retinitis pigmentosa and diabetes-related blindness.

The results of the study have just been published in Nature (April 18), “Restoration of Vision After Transplantation of Photoreceptors”.

More information about this discovery can be read in the news release put out by UCL:


Photoreceptor transplant restores vision in mice
18 April 2012

Scientists from the UCL Institute of Ophthalmology have shown for the first time that transplanting light-sensitive photoreceptors into the eyes of visually impaired mice can restore their vision. The research, published in Nature, suggests that transplanting photoreceptors - light-sensitive nerve cells that line the back of the eye - could form the basis of a new treatment to restore sight in people with degenerative eye diseases.

Scientists injected cells from young healthy mice directly into the retinas of adult mice that lacked functional rod-photoreceptors. Loss of photoreceptors is the cause of blindness in many human eye diseases including age-related macular degeneration, retinitis pigmentosa and diabetes-related blindness.

There are two types of photoreceptor in the eye - rods and cones. The cells transplanted were immature (or progenitor) rod-photoreceptor cells. Rod cells are especially important for seeing in the dark as they are extremely sensitive to even low levels of light.

After four to six weeks, the transplanted cells appeared to be functioning almost as well as normal rod-photoreceptor cells and had formed the connections needed to transmit visual information to the brain.

Transplanted Photoreceptors

The researchers also tested the vision of the treated mice in a dimly lit maze. Those mice with newly transplanted rod cells were able to use a visual cue to quickly find a hidden platform in the maze whereas untreated mice were able to find the hidden platform only by chance after extensive exploration of the maze.

Professor Robin Ali at UCL Institute of Ophthalmology, who led the research, said: "We've shown for the first time that transplanted photoreceptor cells can integrate successfully with the existing retinal circuitry and truly improve vision. We're hopeful that we will soon be able to replicate this success with photoreceptors derived from embryonic stem cells and eventually to develop human trials."

"Although there are many more steps before this approach will be available to patients, it could lead to treatments for thousands of people who have lost their sight through degenerative eye disorders. The findings also pave the way for techniques to repair the central nervous system as they demonstrate the brain's amazing ability to connect with newly transplanted neurons."

Dr Rachael Pearson from UCL Institute of Ophthalmology and principal author, said: "We are now finding ways to improve the efficiency of cone photoreceptor transplantation and to increase the effectiveness of transplantation in very degenerate retina. We will probably need to do both in order to develop effective treatments for patients."

Dr Rob Buckle, head of regenerative medicine at the Medical Research Council (MRC) said: "This is a landmark study that will inform future research across a wide range of fields including vision research, neuroscience and regenerative medicine. It provides clear evidence of functional recovery in the damaged eye through cell transplantation, providing great encouragement for the development of stem cell therapies to address the many debilitating eye conditions that affect millions worldwide."

The researchers demonstrated previously, in another study published in Nature,  that it is possible to transplant photoreceptor cells into an adult mouse retina, provided the cells from the donor mouse are at a specific stage of development - when the retina is almost, but not fully, formed. In this study they optimised the rod transplantation procedure to increase the number of cells integrated into the recipient mice and so were able to restore vision.

The research was funded by the MRC, the Wellcome Trust, the Royal Society, the British Retinitis Pigmentosa Society, Alcon Research Institute and The Miller's Trust. Robin Ali is a senior investigator of the National Institute for Health Research and carries out research at the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. Rachael Pearson is a Royal Society University Research Fellow.


Saturday, April 14, 2012

A Searchable Archive of Medical/Surgical/Cosmetic Laser Business and Technology News for 1996-2005

Medical Laser Business and Technology News Archive

Archive of Medical/Surgical/Cosmetic Laser Business and Technology News for 1996 - 2005

As with the archive of Ophthalmic Laser Business and Technology News, previously posted on this site (link: http://tinyurl.com/ophthalarchives), I also compiled an archive for the Medical/Sugical/Cosmetic Laser Business and Technology News.

For over ten years, from the Fall of 1995 until December 2005, I wrote and published the monthly Executive Laser Briefing (ELB) newsletter (Figure 1). It was then sold to Trends-in-Medicine and continues to be published as Executive Laser Report (Figure 2).

Figure 1 Executive Laser Briefing

Figure 2 Executive Laser Report

Each issue of ELB contained news releases, analyst reports, and commentary about the various companies and laser technologies making news during that time frame. Each months issue consisted of about 40-50 pages, roughly half of which was about ophthalmic lasers and the remainder about medical/surgical/cosmetic laser information.

At the end of each year, I compiled all of the ophthalmic and medical/surgical news separately, and placed it into a yearly summary. The annual medical/surgical/cosmetic summaries for the years 1995/1996-2005, containing between 100 to 300 pages, are presented below in a publically accessible cloud storage space on Dropbox. (There is only partial information available for 1995, as the newsletter was started in the Fall of that year.)

The medical/surgical archives have also been published by the American Society for Lasers in Medicine and Surgery (ASLMS) on its website (for members only). The ophthalmic laser summaries, as noted above, can be found in a separate archive by following this link.

To access each year’s file, just click on that year’s link and the pdf file should open in an Adobe PDF reader on your browser. You can save each file to your computer and search the archives for a company or type of laser by using either the Adobe search tool or the “find” feature available on each computer (control F).

Irving J. Arons


Searchable Medical/Surgical Archives for 1996 - 2005 at ASLMS (members only)



For Access to these Archives in the Public Domain:

Medical/Surgical Laser Archives for 1996 - 2005


1995/1996 – 109 Pages


1997 – 148 Pages


1998 – 183 Pages


1999 – 233 Pages


2000 – 183 Pages


2001 – 202 Pages


2002 – 225 Pages


2003 – 221 Pages


2004 – 269 Pages


2005 – 261 Pages

Wednesday, April 11, 2012

A Searchable Archive of Ophthalmic Laser Business and Technology News for 1996-2005

Medical Laser Business and Technology News Archive

Archive of Ophthalmic Laser Business and Technology News for 1996-2005


For over ten years, from the Fall of 1995 until December 2005, I wrote and published the monthly Executive Laser Briefing (ELB) newsletter (Figure 1). It was then sold to Trends-in-Medicine and continues to be published as Executive Laser Report (Figure 2).

Figure 1. Executive Laser Briefing

Figure 2. Executive Laser Report

Each issue of ELB contained news releases, analyst reports, and commentary about the various companies and laser technologies making news during that time frame. Each months issue consisted of about 40-50 pages, roughly half of which was about ophthalmic lasers and the remainder about medical/surgical/cosmetic lasers.

At the end of each year, I compiled all of the ophthalmic and medical/surgical news separately, and placed it into a yearly summary. The annual ophthalmic laser summaries for the years 1995/1996-2005, containing between 100 and 300 pages, are presented below in a publically accessible cloud storage space on Dropbox. (There is only partial information available for 1995, as the newsletter was started in the Fall of that year.)

To access each year’s file, just click on that year’s link and the pdf file should open in an Adobe PDF reader on your browser. You can save each file to your computer and search the archives for a company or type of laser by using either the Adobe search tool or the “find” feature available on each computer (control F).

Irving J. Arons

The medical/surgical/cosmetic laser summaries can be found in a separate archive, on the website of the American Society for Laser Medicine and Surgery – link: http://tinyurl.com/aslmsMedSurArchives (members only), or on this online Journal in a separate listing.



Ophthalmic Laser Archives for 1996 - 2005

1995-1996 – 106 Pages

1997 – 101 Pages

1998 – 131 Pages

1999 – 294 Pages

2000 – 328 Pages

2001 – 292 Pages

2002 – 211 Pages

2003 – 262 Pages

2004 – 364 Pages

2005 – 279 Pages

Wednesday, April 04, 2012

Stem Cells in Ophthalmology Update 19: ACT Adds Bascom Palmer as Another Clinical Site for Dry AMD Trials

In an announcement today, Advanced Cell Technology said that Bascom Palmer Eye Institute had received IRB approval to become the third U.S. clinical site for testing ACT’s human embryonic stem cell-derived retinal pigment epithelial cells in the treatment of dry age-related macular degeneration. Bascom Palmer, one of the country’s premier eye institutes, joins UCLA’s Jules Stein Eye Institute and the Wills Eye Institute as the third U.S. site participating in the clinical trials.

The Bascom Palmer trial will be led by acclaimed retinal specialist Dr. Philip Rosenfeld, the father of the use of Avastin in the treatment of the wet form of AMD.

In addition, Moorfields Eye Hospital in London awaits its final approval to join in this important clinical trial for using stem cells in stopping the advancement of the dry form of AMD.

Here is the complete announcement from ACT:


ACT Announces Approval of Bascom Palmer Eye Institute as Additional Site for Stem Cell Clinical Trial for dry Age-Related Macular Degeneration

Ranked as Number One Eye Hospital Eight Years in a Row by U.S. News & World Report, Bascom Palmer Will Participate as Site for ACT's Phase I/II Clinical Trial Using Human Embryonic Stem Cell-Derived RPE Cells for dry AMD

MARLBOROUGH, Mass. - Apr. 4, 2012 - Advanced Cell Technology, Inc., a leader in the field of regenerative medicine, announced today that the Bascom Palmer Eye Institute in Miami, Fla., has received institutional review board (IRB) approval as a site for the company's Phase I/II clinical trial for dry age-related macular degeneration (dry AMD), using human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells.

"We could not be more pleased that the Bascom Palmer Eye Institute has been approved as an additional site for our clinical trial for dry AMD," said Gary Rabin, ACT's chairman and CEO. "The prestigious Bascom Palmer Eye Institute is ranked as the number one ophthalmology hospital in the country by U.S. News & World Report eight years running, and has a particularly strong reputation in the area of macular degeneration. We are very much looking forward to working with Dr. Philip Rosenfeld, a renowned retina specialist and professor of ophthalmology at the University of Miami's Miller School of Medicine, and the rest of his team."

The Phase I/II trial is a prospective, open-label study designed to determine the safety and tolerability of the hESC-derived RPE cells following sub-retinal transplantation into patients with dry AMD. The trial will ultimately enroll 12 patients, with cohorts of three patients each in an ascending dosage format.

Further information about patient eligibility for the dry AMD study is available at www.clinicaltrials.gov; ClinicalTrials.gov Identifier: NCT01344993.

About dry AMD

Degenerative diseases of the retina are among the most common causes of untreatable blindness in the world. Age-related macular degeneration (AMD) is the leading cause of blindness in people over age 60 in the United States, and the vast majority of cases of AMD are of the "dry" form, which is currently untreatable.

About hESC-derived RPE Cells

The retinal pigment epithelium (RPE) is a highly specialized tissue located between the choroids and the neural retina. RPE cells support, protect and provide nutrition for the light-sensitive photoreceptors. Human embryonic stem cells differentiate into any cell type, including RPE cells, and have a similar expression of RPE-specific genes compared to human RPE cells and demonstrate the full transition from the hESC state.

About Advanced Cell Technology, Inc.

Advanced Cell Technology, Inc., is a biotechnology company applying cellular technology in the field of regenerative medicine. For more information, visit www.advancedcell.com.

About Bascom Palmer

Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine - part of UHealth - the University of Miami Health System, is ranked the best eye hospital in the nation, as published in U.S. News & World Report. Having earned an international reputation as one of the premier providers of eye care in the world, Bascom Palmer is also ranked #1 in patient care and residency training by Ophthalmology Times. As the largest ophthalmic care, research and educational facility in the southeastern United States, it treats more than 250,000 patients with nearly every ophthalmic condition each year and more than 12,000 surgeries are performed annually. To date, the Institute has trained more than 900 physicians, clinicians and researchers, many of whom now lead academic and clinical ophthalmology centers worldwide. With nearly 80 faculty members and 1,200 staff, the Institute demonstrates exceptional expertise in every ophthalmic subspecialty. Founded in 1962, Bascom Palmer has patient care facilities in Miami, Palm Beach Gardens, Naples, and Plantation, Florida. For additional information, contact the office of marketing and communications at (305) 326-6190, bpeicommunications@med.miami.edu , or visit www.bascompalmer.org.