Article
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`Lucentis After 1 Year
`Doctors praise this practice-transforming therapy — but find drawbacks.
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`July 1, 2007
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`Lucentis After 1 Year
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`Doctors praise this practice-transforming therapy — but find drawbacks.
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`JERRY HELZNER, SENIOR EDITOR
`
`One year after receiving FDA approval, ranibizumab (Lucentis, Genentech) has already established itself as by far
`the predominant first-line treatment for the wet form of age-related macular degeneration (AMD). The drug has
`brought new hope for improved vision to patients who had little hope before and has given retina specialists a
`potent new weapon with which to fight the anticipated increase in wet AMD cases as the huge baby boomer
`generation enters its senior years.
`
`The numbers speak for themselves. Ranibizumab is on track to produce approximately $800 million in first-year
`sales for Genentech. The competing AMD drug pegaptanib sodium (Macugen, OSI Pharmaceuticals/Pfizer)
`recently recorded quarterly US sales of $7 million and verteporfin for injection (Visudyne, QLT/Novartis), is
`currently tracking US sales at about $8.4 million per quarter.
`
`DOCTORS SEE DRAWBACKS
`
`Though retina specialists are quick to praise ranibizumab as an effective and practice-transforming therapy, recent
`interviews with retina specialists conducted by this publication point to concerns about ranibizumab, primarily
`centering on too-frequent patient visits for repeat injections, unrealistic patient expectations, and the major
`financial issues that stocking and billing the drug entails. Indeed, doctors interviewed by Retinal Physician for this
`article would like to see a wet AMD drug approved in the next 5 years that requires fewer injections and is less
`expensive. Longer term, they see the ideal treatment for the disease as an oral or topical therapy.
`
`Retina specialists' mixed feelings about ranibizumab are clearly demonstrated in the following 2 quotes from
`Andrew Antoszyk, MD, who has served as lead investigator in the longest duration study of the safety and efficacy
`of ranibizumab, following some patients for as long as 3.8 years.
`
`"Lucentis ranks up there with other milestones in the management of various medical disorders," says Dr.
`Antoszyk. "It has been capable of not only preventing severe vision loss in patients with wet AMD but has allowed
`many individuals to experience a significant degree of visual improvement. I definitely consider Lucentis a practice-
`transforming therapy."
`
`But this also from Dr. Antoszyk:
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`Exhibit 2106
`Page 01 of 04
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`"Lucentis has several drawbacks. One, it requires a patient to come back on a relatively frequent basis (every 4 to
`6 weeks), which places a tremendous burden either on the patients themselves and/or their families. In addition,
`there are financial concerns involved with these repeat treatments that not only include the cost of the drug but the
`associated ancillary testing and clinical exams required to monitor the therapy. One of the problems with Lucentis
`is having to carry a large inventory, which is a significant cost.
`
`"Although there are also theoretical drawbacks to the use of pan-VEGF-A blockade, these are yet to be proven.
`The potential increased risk of cerebrovascular events in patients receiving intravitreal Lucentis is of concern,
`although the rate is low and not above what is expected for this age group."
`
`TOO MANY PATIENT VISITS
`
`Of the several drawbacks to ranibizumab mentioned by retina specialists, it is dealing with the day-to-day
`disruptions of increased patient flow that distresses them the most.
`
`"The need for multiple treatments at 4-week intervals with no definite endpoint is a significant drawback," says
`Sharon Fekrat, MD.
`
`"Frequency of patient visits is definitely an issue with Lucentis, says Henry Hudson, MD. "Even if you use OCT
`(optical coherence tomography) to determine the timing of retreatments, you may not be giving a patient injections
`every month but you are still scheduling the visits to monitor disease progression."
`
`For its part, Genentech says it recognizes the burden the repeated treatments puts on physicians and their
`practice and is working with the retina community to evaluate less frequent dosing regimens.
`
`Dr. Hudson also cites unrealistic patient expectations for ranibizumab treatment.
`
`"Expectations are very high now. Everyone who comes in for treatment knows someone who has done well with
`Lucentis," he notes. "Some patients, who don't see improvement after the first injection, want to be switched to
`another therapy. It is a concern, but then again, patients also had high expectations when PDT (photodynamic
`therapy) was first introduced."
`
`Generally, retina specialists now see ranibizumab as the standard of care for first-line treatment of wet AMD.
`Physicians who previously used bevacizumab (Avastin, Genentech) to treat wet AMD patients have cut back
`sharply on their use of that drug because ranibizumab is an approved therapy that is more easily reimbursed.
`
`"Prior to Lucentis approval, Avastin was our standard (wet AMD) treatment," says Robert Avery, MD. "After
`approval, many patients elected to be treated with Lucentis due to its FDA approval and its impressive benefit
`demonstrated by well-done randomized controlled clinical trials. What has changed in the exam lane is a longer
`discussion of the differences between well-studied Lucentis and lower-cost Avastin. After the discussion, I let the
`patient decide upon which agent to use. Those who choose Avastin often do so for financial reasons or because
`they have done well with it in the past and do not want to change."
`
`Though there is now anecdotal data that ranibizumab can be effective in treating other retinal diseases, particularly
`diabetic macular edema (DME), doctors are not using it for other retinal diseases because it is not approved for
`other indications and is too expensive to use without the possibility of reimbursement. However, trials are
`continuing using ranibizumab to treat DME and vein occlusions.
`
`COMBINATIONS BEING TRIED
`
`Ranibizumab is now being used as part of combination therapy, almost always when the patient does not show
`improvement on ranibizumab monotherapy.
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`Exhibit 2106
`Page 02 of 04
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`"I only use Lucentis in combination if the patient does not appear to be responding to Lucentis alone," says Paul
`Sternberg Jr., MD. "In most cases, I have tried PDT."
`
`A number of other retina specialists have recently begun using so-called "triple therapy" — a combination of
`ranibizumab, reduced-fluence PDT, and dexamethasone that is now the subject of several ongoing studies.
`
`Ranibizumab retreatment schedules are being determined by several methods. Some physicians report that they
`follow the recommended dosing schedule of retreatment every 4 weeks. Others, such as Allen Ho, MD, use a
`combination of examination, visual acuity measurement, OCT monitoring, and sometimes fluorescein angiography
`to determine when retreatment is necessary.
`
`"Fluorescein angiography helps to look for leakage not identified on OCT and for increasing size of the
`neovascularization," adds Dr. Antoszyk. "We are continuing to monitor and observe for evidence of progression of
`the dry component of AMD. It is highly likely that this (the dry) will continue to progress, even in the presence of
`inhibited neovascularization."
`
`LOOKING AHEAD
`
`In regard to the need for other therapies that are alternatives to Lucentis becoming available in the next 5 years,
`some respondents point to VEGF Trap (Regeneron), which is now moving into a phase 3 trial. Although
`significantly more testing is required, VEGF Trap may offer the potential to improve vision with a regular dosing
`regimen that is less frequent than monthly.
`
`However, Dr. Ho believes that there is only a small chance that a new monotherapy will supplant ranibizumab in
`the next 5 years, though he notes that new treatment combinations that include ranibizumab may prove to be more
`effective than Lucentis alone.
`
`Retina specialists are also eager to see the ranibizumab/bevacizumab head-to-head, sponsored by the National
`Institutes of Health, commence.
`
`"I think that this study is outstanding and needs to be done," says Dr. Fekrat. "I hope it gets funded."
`
`"It's a very important study," adds Dr. Ho. "But it's too slow to get going."
`
`"If the 2 drugs are proven to be of equal benefit, Avastin would be the choice because it's much cheaper," notes
`Dr. Hudson."
`
`Finally, practices are still wrestling with the economic aspects of stocking ranibizumab and receiving equitable
`reimbursement.
`
`"Numerous financial headaches have been highlighted by the rapid adoption of Lucentis therapy," says Dr. Avery.
`"Many practices are losing money on the handling of the drug as the 6% profit spread has been reduced to 4%,
`and this may not cover the cost of collections and unpaid claims.
`
`"Of course this depends upon the payer mix and the efficiency of the practice, but in my experience, for most
`primary payers other than Medicare, the effort required by my billing staff has been excessive this first year. I
`expect this to improve when there is a J code for Lucentis in the future. Regardless, there will be a problem with
`certain HMOs or IPAs who do not want to pay for expensive therapies. Certain states have a tax on medical
`reimbursements which cut into the slim 'profit margin,' and even universities must carve the payments out of the
`dean's tax. Fortunately, Genentech has tried to help with generous plans for the uninsured patients."
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`Exhibit 2106
`Page 03 of 04
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`Despite these problems, by any reasonable measure, having ranibizumab approved and widely available to treat
`wet AMD for the past 12 months has overall been a major plus for the retina community and for patients. Whether
`ranibizumab retains its dominance or yields its place to a more effective, more efficient, or less costly therapy will
`be determined in the months and years ahead. RP
`
`Retinal Physician, Issue: July / Aug 2007
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`Exhibit 2106
`Page 04 of 04
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