Visudyne: A Cautionary Tale
As the first combination therapy for age-related macular degeneration (AMD), an eye condition that can eventually lead to
blindness, Visudyne, like Cypher, represented a first-to-market breakthrough technology. In contrast, Visudyne's road to reimbursement
was a long and bumpy one, marked by numerous gaps between what CMS wanted and what was delivered.
Biotech company QLT developed Visudyne specifically for "wet" AMD. In patients with this disease, abnormal blood vessels grow
in the eye and then leak, ultimately resulting in blindness. Roughly a quarter of a million Americans over age 65 were afflicted.
Visudyne was injected in the eye then activated using a laser administered at a specific frequency. Visudyne couldn't stop
the disease, but it significantly slowed its progress. Novartis acquired the Visudyne trademark in late 2000 when it bought
FDA and CMS recognize different indications within wet AMD. These are known as "predominantly classic" (CNV), "minimally classic,"
and "occult," based on lesion size. Predominantly classic cases, which are easiest to detect, account for roughly 25 percent
of potential patients, while the occult segment accounts for roughly twice as many patients. Visudyne received FDA approval
for predominantly classic wet AMD in April 2000 and CMS approval for this same category in November 2000.
But since many doctors began to prescribe the drug off-label for occult and minimally classic lesions, the company continued
to seek CMS reimbursement for off-label use. In subsequent reviews in November 2000, October 2001, March 2002, and January
2004, attempts were made to broaden coverage; all were rejected on the basis of methodological shortcomings in the data presented.
CMS' national coverage decision highlights the kinds of concerns that were raised. The time frame for data collection was
deemed too short (no data was available after 24 months). Definition of treatment outcomes that would prompt cessation of
Visudyne use had not been provided, and no guidance was given for the appropriate frequency of additional treatment. The Visudyne
project team had suggested that additional treatment be given if CNV leakage was detected by a fluorescein angiogram. However,
because there was no patient follow-up beyond the two-year trial period, it was impossible to estimate the implications this
guidance would be expected to have on the average number of required treatments per patient or how additional treatment would
improve patient outcomes. The fact that fluorescein angiograms are quite subjective and can lead to false negative and positive
diagnoses was a strong factor in CMS' 2000 decision to restrict coverage to patients with predominantly classic CNV lesions.
Ultimately, in 2004, CMS approved Visudyne for occult and minimally classic types, but only under specific circumstances and
monitoring conditions. CMS' reimbursement conditions are over and above FDA guidelines, and have had the effect of restricting
coverage to a little over 50 percent of those patients who might otherwise have been eligible.
From the perspective of QLT, the broadening of coverage to include off-label indications and up to 50 percent of the target
population was a victory. Similarly, much of the "gap" between what CMS wanted and what QLT provided by way of data has been
ascribed to the novelty of the treatment area for wet AMD and the evolution of CMS' requirements as it became familiar with
the clinical details.
Still, from a strategic reimbursement perspective, waiting four years to get coverage for half of the total projected market
was a clear failure that blocked this product from obtaining its financial objectives. As it could not promote off-label use,
QLT was constrained in its marketing, and patients had to pay for treatment out of their own pockets. Delays and restrictions
on CMS coverage also indirectly constricted Visudyne's success in the US, as its decisions have a strong influence on other
While the project team scrambled to gather more suitable evidence and various constituents initiated legal proceedings to
pressure CMS to reconsider Visudyne's case for reimbursement, the competition began to catch up. Pfizer's Macugen received
FDA approval in December 2004, and CMS coverage in February 2005. Less than one year after Visudyne gained coverage for a
sizable chunk of CMS' AMD patients, Macugen had gained coverage access to all of them. QLT's shares had risen to $115 after
FDA approval in mid-2000, reflecting the market's anticipation of a new revenue stream. Since then it has slid. As 2005 drew
to a close, it was below $8.
The lesson? Particularly for companies with a limited product portfolio, narrowly defining reimbursement strategy can carry
Checklist for State-of-the-Art P&R
The ascendancy of payers as a negotiating power, the focus of healthcare reform on limiting costs, and the growth of cost-effectiveness
agencies with a mandate to screen medicines for access to patients suggests that reimbursement strategy will be vital to commercial
success in the future. Decisions that don't show hard evidence of economic and clinical value are a receding memory; companies
will have to reorient their thinking about the business along the lines of value delivered.
That said, what conclusions can be drawn from these two examples on what constitutes best-practice in strategic reimbursement?
- Reimbursement planning no longer begins at the point of commercialization; it has to be part of the portfolio development
process. As new information becomes available in clinical development, reimbursement input should inform decision making.
- Strategic reimbursement must establish and maintain close contact with payers, government agencies, and relevant professional
and patient organizations, soliciting and using their input across the product development process. Equally important, the
development of trust and credibility is an important base on which to build the case for both approval and reimbursement.
- As commercialization approaches, strategic reimbursement must play a role in articulating value propositions appropriate for
all relevant constituencies, and in formulating plans to communicate them.
- Strategic reimbursement must drive fresh thinking about the collection of data on economic and clinical value, and effective
presentation of such data to position products for reimbursement.
- The evolving strategic role of reimbursement call for a significantly broader range of competencies and a new set of expectations
than has been the norm. Such "gaps" will need to be addressed through a thorough redefinition of reimbursement roles, requirements,
and key accountabilities, along with selection and development processes to support staffing.
- Given the increased centrality of the function, reimbursement should be reconfigured as part of a strategic market-access
function to ensure that its visibility and input are appropriate to evolving market demands.
Marketing and reimbursement need to take the lead in establishing a value-driven approach to the business that ensures identification
and focus on economic, clinical, and other benefits to critical constituencies that can be used to influence overall regulatory,
reimbursement, and market acceptance of the product. Among other approaches, this can include tactics like "service wraps"
that bring additional value to key channel segments to differentiate and enhance product attractiveness.
is managing partner of Numerof & Associates. Rita Numerof is president of Numerof & Associates. They can be reached at