Visudyne looks promising for treating wet AMD

But will the new procedure break the Medicare bank? With 65,000 procedures performed in 2000, the question is apt.

Last year at this time I reported that Visudyne photodynamic therapy (PDT), along with several other PDT treatments in the pipeline, appeared promising for those afflicted with predominantly classic, wet age-related macular degeneration. This year the technology has come to the market, and good results are being reported but financial questions remain.

My earlier report was filed following the 1999 American Academy of Ophthalmology (AAO) meeting (“Laser treatments for AMD show promise,” Jan. 15, 2000, issue), One question posed by industry analysts during that meeting was how, when these new techniques came to market, would the Health Care Financing Administration (HCFA) handle the reimbursement issues without bankrupting Medicare?

Well, the inevitable has happened. Visudyne therapy (verteporfin for injection, marketed for QLT Inc. by CIBA Vision) for predominantly classic wet AMD was approved for marketing by the Food and Drug Administration in April 2000. Since then, thousands of AMD patients have flooded retinal surgeons’ offices seeking treatment.

The approval was based on the 12-month data from two 24-month randomized, double-masked, placebo-controlled phase 3 clinical trials known as the Treatment of AMD with Photodynamic therapy (TAP) Investigation. Results of the TAP studies were published in the October 1999 issue of Archives of Ophthalmology. The TAP 12-month findings showed that in 243 patients with predominantly classic wet choroidal neovascularization (CNV), vision remained stable or improved in 67% of patients treated with Visudyne therapy versus 39% of patients in the placebo arm of the study. Additional data released this past summer showed that the beneficial effect and the favorable safety profile of Visudyne therapy that was observed at the 12-month time point was maintained out to 2 years, with fewer treatments required in the second year (see clinical results update below).

Market size and reimbursement

It is estimated that some 65,000 U.S. PDT treatments, both primary and retreatments, were done in 2000, producing $90 million to $100 million in drug revenues for QLT/CIBA Vision. If analysts’ projections continue to hold up, the drug could reach more than $200 million in sales in 2001 — and as high as $500 to $700 million by 2003.

But the picture isn’t all rosy. In November, HCFA issued its revised National Policy for Reimbursement, calling Visudyne therapy a “medically reasonable and necessary treatment.” The agency also expanded somewhat the number of patients who can receive treatment (those presenting with at least 50% classic symptoms from a fluorescein angiogram) and how often retreatments can occur — up to 6 treatments over 24 months, although recent field interviews/surveys show that fewer retreatments are occurring in practice over an extended time. (The TAP inclusion criteria included having visual acuities between 20/40 and 20/200, and lesions greater in size than 0.5 mm. On average, 5.6 treatments were reported over the 2-year period.)

However, the agency cut the expected physician reimbursement for the treatment — including infusion, use of the laser and staff overheads — to $341 from the $500-to-$700 reimbursement figure expected (and previously paid for laser photocoagulation). When added to the drug reimbursement ($1,458), Visudyne PDT therapy total reimbursement will be $1,799 in 2001. Taken against the cost to administer the treatment, according to a Dain Rauscher Wessels analysis, a high-volume practice could expect a profit per procedure of about $500, while a low-volume practice might only clear $135, not including the physician’s fee! This total is down from the $900 profit that high-volume practices could have expected under the older laser photocoagulation rates, and about $550 for lower-volume practices.

With between 1,200 and 1,300 practicing retinal specialists in the United States, we estimate that there are currently about 600 PDT activation lasers (from either Zeiss Humphrey or Coherent Medical) in use in the United States, with an additional 600 in use worldwide.

In a poll of 67 retinal practices conducted by Leerink Swann & Company in November 2000, 82% of respondents stated that the new level of reimbursement from HCFA was below expectations and inadequate. At an AMD press conference held during this year’s AAO meeting before the HCFA announcement, Mark Blumenkranz, MD, noted that Visudyne treatment may end up being offered only at larger medical centers or academic centers if the reimbursement issues are not satisfactorily resolved.

Medicare cost

I have attempted to calculate the potential cost to the Medicare system for PDT for the year 2000 and beyond. The cost for 2000 depends on how many people actually underwent the treatment, which in turn depends on how many of the 200,000 to 350,000 of the current AMD pool met the acceptance criteria. The wet form of AMD accounts for about 10% to 15% of the total AMD population, or 1.3 to 1.5 million people in the United States, plus another 200,000 new cases diagnosed each year (and 400,000 more worldwide). The predominantly classic form represents about 10% to 15% of the total wet form population, or approximately 130,000 to 250,000 people that could now be treated, with an additional 20,000 to 30,000 being diagnosed and entering the potential treatment pool each year, not taking into account additional patients with diseases such as pathological myopia, which should be added to the Visudyne labeling sometime in mid-2001.

The cost to Medicare for Visudyne PDT in 2000 could conceivably have ranged from $160 million to $280 million, assuming that one-third of the current pool elected treatment, half of those were eligible (many in the pool may have already lost too much vision to be treatable) and the cost to the system is $1,799 per procedure ($1,458 for the drug — or less depending on the copay — plus $341 for treatment) with an average of three treatments needed over the course of the first year. (This calculation assumes that 60% of recipients have Medicaid and Medicare pays 80% of the drug cost, with the recipient paying the remaining 20% co-pay. The actual cost for 2000, based on 65,000 doses, was closer to $115 million.)

In subsequent years, with another third of those eligible entering treatment, along with additional retreatments for some of those already started on their initial course of treatment, Medicare costs could average over $250 million a year. And when other eye diseases and treatment modalities are approved, the cost can only rise. Another factor is the subjective nature of the diagnosis. Those patients with marginal classic symptoms may be included in the treatment class, as this might be their only hope for retaining vision.

Improved quality of life

On a more positive note, Dr. Sanjay Sharma of Queens University in Kingston, Ontario, presented a paper during the AAO meeting on a decision-making model for measuring the impact of Visudyne therapy on the quality of life of those with AMD. He concluded that PDT is a very effective treatment for AMD, and that patients who are still able to drive could expect a 10.7% improvement in quality of life if they received the treatment, while patients who were legally blind could expect a 7.8% improvement. This compares to those who have lost significant vision, who are assessed as having a 40% reduction in their quality of life.

With the looming crisis in vision loss as baby boomers advance into their middle and senior years over the next decade, more than 500,000 people a year will be diagnosed with AMD, and without treatment will become more dependent on others (and possibly on the welfare system). As Dr. Sharma’s model suggests, “For one patient with macular degeneration to obtain one quality of life-adjusted year, PDT will cost a managed care organization $86,721. If the treatment proves effective over the entire duration of a patient’s life, this cost will fall dramatically.” Left unsaid is the potential cost to the system for legally blind people unable to avail themselves of the treatment.

Clinical update — PDT trials

During the AAO Vitreoretinal Update meeting, Susan Bressler, MD, provided 24-month data for the TAP study. The data reiterated the significant difference in eyes treated with PDT versus the placebo control, with 53% of the Visudyne patients losing less than 15 letters (three lines) of visual acuity, compared to 38% for the placebo group. The subgroup results for predominantly classic patients showed even better results, but they were not so good for those with minimally classic or nonclassic disease. For those with predominantly classic lesions, 59% lost less than 15 letters, versus 31% of the placebo group; in the minimally classic group, 48% lost less than 15 letters, versus 44% getting the placebo; and 56% versus 30% for the nonclassic disease group.

Dr. Bressler concluded that the results seen at 12 months were sustained at 24 months, with even more compelling evidence to use Visudyne therapy for patients with classic wet AMD. The additional benefits of the 24-month TAP trial were limited, but included slower lesion growth, reduced leakage and stable contrast sensitivity. The average number of treatments of the group during the second year was 2.2 out of a possible maximum of 4, resulting in an average number of treatments over the 2-year period of 5.6 out of a maximum of 8.

Joan Miller, MD, reported on the 12-month results of the Verteporfin in Photodynamic Therapy (VIP) study for pathologic myopia taking place at 28 clinical centers worldwide. In this case, 72% of those treated achieved less than 8 letter loss (less than 1.5 lines) compared to 44% in the placebo group. Dr. Miller concluded that VIP treatment resulted in a significantly increased incidence of stability or improved visual acuity, with no evidence of ocular or systemic tissue risk. The VIP trial was focused on two groups of patients; those with pathologic myopia and those with earlier stage AMD than in the TAP study (that is, either those with occult lesions or those with classic lesions but better than 20/40 vision). While the VIP trial was intended to expand the population for Visudyne-eligible patients, it was less definitive than TAP. Statistical benefits were experienced among those in the pathologic myopia group, but there were no statistically significant differences or advantages for those with earlier stage AMD treated with Visudyne compared to placebo.

At the AAO’s AMD press conference, Dr. Blumenkranz, coordinator for the Pharmacyclics/Alcon Labs trials of Optrin (LuTex), said that the phase 1 and 2 clinical trials for that drug had been completed and were being evaluated prior to recruiting patients for phase 3 trials. (It was also learned that a Zeiss diode laser is being used for activation, not the Diomed system as reported in my article last year.)

Edgar Thomas, MD, head of the Miravant/Pharmacia & Upjohn trial of Photopoint (purlytin), said the drug was completing phase 3 trials with nothing new to report.

Laser treatments

Elias Reichel, MD, reported on the results to date in the ongoing multicenter clinical trial to treat occult wet AMD, the most prevalent form of the disease, with low-intensity laser energy, in the transpupillary thermotherapy (TTT) for CNV trial. Unlike PDT, this trial used the Iridex Iris Medical SLx 810 nm diode laser in its unique long-pulse mode to treat the lesions without the need for a photoactive drug. He reported that after 1 year, 80% of patients with occult wet AMD treated with the laser experienced a halt in new vessel growth and that 70% had stable or improved vision, with no signs of damage to the photoreceptor cells of the retina. TTT appears to stop the evolution of the exudative process, and may avoid development of or progression to the classic form. (Traditionally, half of all cases of occult AMD move into the classic form, with profound visual loss.)

Anecdotal evidence indicates that TTT is doing quite well in the field, but the reimbursement picture remains cloudy. According to Iridex, reimbursements for this treatment, which are left up to the discretion of local Medicare carriers, range from a low of $127 to a high of $700. Until this discrepancy and confusion is cleared up, and published peer-reviewed studies on its success begin to appear, TTT will be slow to be accepted by most retinal surgeons.

Clinical update — dry AMD

At the Iridex booth, a number of speakers provided updates on the ongoing work with both therapeutic and prophylactic treatments for the dry form of AMD. In a pilot study their 810 nm diode laser was used in a grid-pattern therapy on nonexudative soft drusen, with resorption of drusen seen in 68% of treated eyes and visual acuity improvement in 24% of a subset of treated eyes after a single treatment. The company continues to sponsor additional work in both therapeutic and prophylactic trials.

In the therapeutic study, the 4-year follow-up of the original pilot study showed continued improvement in 78% of treated eyes, defined as a reduction of 50% or more of drusen from baseline, versus only 8% of eyes not treated but observed. This resulted in visual acuity improvement by two or more lines in 14% of treated eyes, which suggests a therapeutic benefit for patients with dry AMD who have lost two or more lines of acuity due to the presence of central soft drusen.

In the ongoing prophylactic study, Prophylactic Treatment of AMD, a total of 35 neovascular events have occurred in 4 years in the 22% of eyes nonresponsive to treatment, with half occurring in the observed eyes and half in the treated eyes, indicating no treatment harm or benefit. However, in the 78% of eyes that responded to treatment with a significant reduction in drusen, only one eye developed CNV. The study authors suggest that a prophylactic treatment that effectively promotes drusen resorption may be effective in reducing or delaying progression to CNV.

It is beginning to appear that the once-dreaded AMD disease, and the visual loss accompanying it in its worst cases, will become treatable for the vast majority of those who contract it over the next decade.

This calculation assumes (or less, depending on the co-pay).

For Your Information:
  • Irving J. Arons is managing director of Spectrum Consulting with offices at 4 Harvard St., Peabody, MA 01960; phone and fax: (978) 531-0939; e-mail: iarons@erols.com. Mr. Arons has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Last year at this time I reported that Visudyne photodynamic therapy (PDT), along with several other PDT treatments in the pipeline, appeared promising for those afflicted with predominantly classic, wet age-related macular degeneration. This year the technology has come to the market, and good results are being reported but financial questions remain.

My earlier report was filed following the 1999 American Academy of Ophthalmology (AAO) meeting (“Laser treatments for AMD show promise,” Jan. 15, 2000, issue), One question posed by industry analysts during that meeting was how, when these new techniques came to market, would the Health Care Financing Administration (HCFA) handle the reimbursement issues without bankrupting Medicare?

Well, the inevitable has happened. Visudyne therapy (verteporfin for injection, marketed for QLT Inc. by CIBA Vision) for predominantly classic wet AMD was approved for marketing by the Food and Drug Administration in April 2000. Since then, thousands of AMD patients have flooded retinal surgeons’ offices seeking treatment.

The approval was based on the 12-month data from two 24-month randomized, double-masked, placebo-controlled phase 3 clinical trials known as the Treatment of AMD with Photodynamic therapy (TAP) Investigation. Results of the TAP studies were published in the October 1999 issue of Archives of Ophthalmology. The TAP 12-month findings showed that in 243 patients with predominantly classic wet choroidal neovascularization (CNV), vision remained stable or improved in 67% of patients treated with Visudyne therapy versus 39% of patients in the placebo arm of the study. Additional data released this past summer showed that the beneficial effect and the favorable safety profile of Visudyne therapy that was observed at the 12-month time point was maintained out to 2 years, with fewer treatments required in the second year (see clinical results update below).

Market size and reimbursement

It is estimated that some 65,000 U.S. PDT treatments, both primary and retreatments, were done in 2000, producing $90 million to $100 million in drug revenues for QLT/CIBA Vision. If analysts’ projections continue to hold up, the drug could reach more than $200 million in sales in 2001 — and as high as $500 to $700 million by 2003.

But the picture isn’t all rosy. In November, HCFA issued its revised National Policy for Reimbursement, calling Visudyne therapy a “medically reasonable and necessary treatment.” The agency also expanded somewhat the number of patients who can receive treatment (those presenting with at least 50% classic symptoms from a fluorescein angiogram) and how often retreatments can occur — up to 6 treatments over 24 months, although recent field interviews/surveys show that fewer retreatments are occurring in practice over an extended time. (The TAP inclusion criteria included having visual acuities between 20/40 and 20/200, and lesions greater in size than 0.5 mm. On average, 5.6 treatments were reported over the 2-year period.)

However, the agency cut the expected physician reimbursement for the treatment — including infusion, use of the laser and staff overheads — to $341 from the $500-to-$700 reimbursement figure expected (and previously paid for laser photocoagulation). When added to the drug reimbursement ($1,458), Visudyne PDT therapy total reimbursement will be $1,799 in 2001. Taken against the cost to administer the treatment, according to a Dain Rauscher Wessels analysis, a high-volume practice could expect a profit per procedure of about $500, while a low-volume practice might only clear $135, not including the physician’s fee! This total is down from the $900 profit that high-volume practices could have expected under the older laser photocoagulation rates, and about $550 for lower-volume practices.

With between 1,200 and 1,300 practicing retinal specialists in the United States, we estimate that there are currently about 600 PDT activation lasers (from either Zeiss Humphrey or Coherent Medical) in use in the United States, with an additional 600 in use worldwide.

In a poll of 67 retinal practices conducted by Leerink Swann & Company in November 2000, 82% of respondents stated that the new level of reimbursement from HCFA was below expectations and inadequate. At an AMD press conference held during this year’s AAO meeting before the HCFA announcement, Mark Blumenkranz, MD, noted that Visudyne treatment may end up being offered only at larger medical centers or academic centers if the reimbursement issues are not satisfactorily resolved.

Medicare cost

I have attempted to calculate the potential cost to the Medicare system for PDT for the year 2000 and beyond. The cost for 2000 depends on how many people actually underwent the treatment, which in turn depends on how many of the 200,000 to 350,000 of the current AMD pool met the acceptance criteria. The wet form of AMD accounts for about 10% to 15% of the total AMD population, or 1.3 to 1.5 million people in the United States, plus another 200,000 new cases diagnosed each year (and 400,000 more worldwide). The predominantly classic form represents about 10% to 15% of the total wet form population, or approximately 130,000 to 250,000 people that could now be treated, with an additional 20,000 to 30,000 being diagnosed and entering the potential treatment pool each year, not taking into account additional patients with diseases such as pathological myopia, which should be added to the Visudyne labeling sometime in mid-2001.

The cost to Medicare for Visudyne PDT in 2000 could conceivably have ranged from $160 million to $280 million, assuming that one-third of the current pool elected treatment, half of those were eligible (many in the pool may have already lost too much vision to be treatable) and the cost to the system is $1,799 per procedure ($1,458 for the drug — or less depending on the copay — plus $341 for treatment) with an average of three treatments needed over the course of the first year. (This calculation assumes that 60% of recipients have Medicaid and Medicare pays 80% of the drug cost, with the recipient paying the remaining 20% co-pay. The actual cost for 2000, based on 65,000 doses, was closer to $115 million.)

In subsequent years, with another third of those eligible entering treatment, along with additional retreatments for some of those already started on their initial course of treatment, Medicare costs could average over $250 million a year. And when other eye diseases and treatment modalities are approved, the cost can only rise. Another factor is the subjective nature of the diagnosis. Those patients with marginal classic symptoms may be included in the treatment class, as this might be their only hope for retaining vision.

Improved quality of life

On a more positive note, Dr. Sanjay Sharma of Queens University in Kingston, Ontario, presented a paper during the AAO meeting on a decision-making model for measuring the impact of Visudyne therapy on the quality of life of those with AMD. He concluded that PDT is a very effective treatment for AMD, and that patients who are still able to drive could expect a 10.7% improvement in quality of life if they received the treatment, while patients who were legally blind could expect a 7.8% improvement. This compares to those who have lost significant vision, who are assessed as having a 40% reduction in their quality of life.

With the looming crisis in vision loss as baby boomers advance into their middle and senior years over the next decade, more than 500,000 people a year will be diagnosed with AMD, and without treatment will become more dependent on others (and possibly on the welfare system). As Dr. Sharma’s model suggests, “For one patient with macular degeneration to obtain one quality of life-adjusted year, PDT will cost a managed care organization $86,721. If the treatment proves effective over the entire duration of a patient’s life, this cost will fall dramatically.” Left unsaid is the potential cost to the system for legally blind people unable to avail themselves of the treatment.

Clinical update — PDT trials

During the AAO Vitreoretinal Update meeting, Susan Bressler, MD, provided 24-month data for the TAP study. The data reiterated the significant difference in eyes treated with PDT versus the placebo control, with 53% of the Visudyne patients losing less than 15 letters (three lines) of visual acuity, compared to 38% for the placebo group. The subgroup results for predominantly classic patients showed even better results, but they were not so good for those with minimally classic or nonclassic disease. For those with predominantly classic lesions, 59% lost less than 15 letters, versus 31% of the placebo group; in the minimally classic group, 48% lost less than 15 letters, versus 44% getting the placebo; and 56% versus 30% for the nonclassic disease group.

Dr. Bressler concluded that the results seen at 12 months were sustained at 24 months, with even more compelling evidence to use Visudyne therapy for patients with classic wet AMD. The additional benefits of the 24-month TAP trial were limited, but included slower lesion growth, reduced leakage and stable contrast sensitivity. The average number of treatments of the group during the second year was 2.2 out of a possible maximum of 4, resulting in an average number of treatments over the 2-year period of 5.6 out of a maximum of 8.

Joan Miller, MD, reported on the 12-month results of the Verteporfin in Photodynamic Therapy (VIP) study for pathologic myopia taking place at 28 clinical centers worldwide. In this case, 72% of those treated achieved less than 8 letter loss (less than 1.5 lines) compared to 44% in the placebo group. Dr. Miller concluded that VIP treatment resulted in a significantly increased incidence of stability or improved visual acuity, with no evidence of ocular or systemic tissue risk. The VIP trial was focused on two groups of patients; those with pathologic myopia and those with earlier stage AMD than in the TAP study (that is, either those with occult lesions or those with classic lesions but better than 20/40 vision). While the VIP trial was intended to expand the population for Visudyne-eligible patients, it was less definitive than TAP. Statistical benefits were experienced among those in the pathologic myopia group, but there were no statistically significant differences or advantages for those with earlier stage AMD treated with Visudyne compared to placebo.

At the AAO’s AMD press conference, Dr. Blumenkranz, coordinator for the Pharmacyclics/Alcon Labs trials of Optrin (LuTex), said that the phase 1 and 2 clinical trials for that drug had been completed and were being evaluated prior to recruiting patients for phase 3 trials. (It was also learned that a Zeiss diode laser is being used for activation, not the Diomed system as reported in my article last year.)

Edgar Thomas, MD, head of the Miravant/Pharmacia & Upjohn trial of Photopoint (purlytin), said the drug was completing phase 3 trials with nothing new to report.

Laser treatments

Elias Reichel, MD, reported on the results to date in the ongoing multicenter clinical trial to treat occult wet AMD, the most prevalent form of the disease, with low-intensity laser energy, in the transpupillary thermotherapy (TTT) for CNV trial. Unlike PDT, this trial used the Iridex Iris Medical SLx 810 nm diode laser in its unique long-pulse mode to treat the lesions without the need for a photoactive drug. He reported that after 1 year, 80% of patients with occult wet AMD treated with the laser experienced a halt in new vessel growth and that 70% had stable or improved vision, with no signs of damage to the photoreceptor cells of the retina. TTT appears to stop the evolution of the exudative process, and may avoid development of or progression to the classic form. (Traditionally, half of all cases of occult AMD move into the classic form, with profound visual loss.)

Anecdotal evidence indicates that TTT is doing quite well in the field, but the reimbursement picture remains cloudy. According to Iridex, reimbursements for this treatment, which are left up to the discretion of local Medicare carriers, range from a low of $127 to a high of $700. Until this discrepancy and confusion is cleared up, and published peer-reviewed studies on its success begin to appear, TTT will be slow to be accepted by most retinal surgeons.

Clinical update — dry AMD

At the Iridex booth, a number of speakers provided updates on the ongoing work with both therapeutic and prophylactic treatments for the dry form of AMD. In a pilot study their 810 nm diode laser was used in a grid-pattern therapy on nonexudative soft drusen, with resorption of drusen seen in 68% of treated eyes and visual acuity improvement in 24% of a subset of treated eyes after a single treatment. The company continues to sponsor additional work in both therapeutic and prophylactic trials.

In the therapeutic study, the 4-year follow-up of the original pilot study showed continued improvement in 78% of treated eyes, defined as a reduction of 50% or more of drusen from baseline, versus only 8% of eyes not treated but observed. This resulted in visual acuity improvement by two or more lines in 14% of treated eyes, which suggests a therapeutic benefit for patients with dry AMD who have lost two or more lines of acuity due to the presence of central soft drusen.

In the ongoing prophylactic study, Prophylactic Treatment of AMD, a total of 35 neovascular events have occurred in 4 years in the 22% of eyes nonresponsive to treatment, with half occurring in the observed eyes and half in the treated eyes, indicating no treatment harm or benefit. However, in the 78% of eyes that responded to treatment with a significant reduction in drusen, only one eye developed CNV. The study authors suggest that a prophylactic treatment that effectively promotes drusen resorption may be effective in reducing or delaying progression to CNV.

It is beginning to appear that the once-dreaded AMD disease, and the visual loss accompanying it in its worst cases, will become treatable for the vast majority of those who contract it over the next decade.

This calculation assumes (or less, depending on the co-pay).

For Your Information:
  • Irving J. Arons is managing director of Spectrum Consulting with offices at 4 Harvard St., Peabody, MA 01960; phone and fax: (978) 531-0939; e-mail: iarons@erols.com. Mr. Arons has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.