Critical Summary:
The CATT Trial: a comparison of Lucentis and Avastin for the
treatment of wet age-related macular degeneration (AMD)
This summary is based on the clinical trial results that were recently published in the New England Journal of Medicine describing the one year results of the CATT trial.
Bay Area Retina Associates provides this summary to aid our patients, our referring doctors, and our community in understanding the results of this important study.
What is the CATT trial?
The
Comparison of
Age-related macular degeneration
Treatments
Trials (CATT) was a large clinical trial
directly comparing two medications that are used the treat neovascular age-related macular degeneration
(wet AMD). The two drugs compared in the study were Avastin (bevacizumab) and Lucentis
(ranibizumab). Both drugs are delivered by intravitreal injection (injection into the eye). Both drugs have
been used for more than 5 years in the treatment of wet AMD, and both drugs are manufactured by
Genentech (now Roche Pharmaceuticals).
The CATT trial compared the two drugs when used every 4 weeks consecutively for one year, and it also
compared the drugs when used only as needed. Consequently, the study compared four different groups
of patients: Lucentis monthly, Lucentis as needed, Avastin monthly, and Avastin as needed. Subjects
received the study treatment in one eye, and all of the results below refer only to the eyes being treated
in this study.
How are Avastin and Lucentis different from each other?
Both drugs inhibit the effects of vascular endothelial growth factor (VEGF), a signaling molecule inside the
eye which contributes to disease activity in wet AMD. By binding VEGF, the drugs decrease the leakage of
fluid and blood which causes central vision loss in wet AMD. The main difference between the two drugs is
their size and strength of binding to VEGF. Both drugs are FDA approved: Lucentis for indications within
the eye including age-related macular degeneration, and Avastin for colorectal cancer.
Lucentis went through large scale clinical trials and was approved by the Food and Drug Administration
(FDA) for the treatment of wet AMD. Avastin was FDA-approved for the treatment of colon cancer via
intravenous infusion, and is used off-label in eyes with wet AMD. Tens of thousands of Avastin injections
have been safely given in the eye, but Avastin has not been studied to the same degree as Lucentis. Prior
to the CATT trial, the two drugs had never been directly compared in a large scale clinical trial. Lucentis
costs approximately $2,000 per dose, while Avastin costs approximately $50 per dose.
Why was the CATT trial conducted?
Because Lucentis costs approximately 200 times as much per dose as Avastin and both drugs are
commonly used throughout the United States to treat wet AMD, the CATT study was funded in order to
determine whether patients with wet AMD could be treated just as successfully with Avastin but at a
much lower cost to patients and insurance companies. Medicare, a federal government program, is the
single largest payer for Lucentis and spent more than $500 million dollars on Lucentis in 2008. The
National Insitutes of Health (NIH), a federally funded research institution, provided much of the funding
for the CATT trial.
What were the results of the CATT trial?
The CATT trial was primarily designed to determine whether Avastin works as well as Lucentis in terms of
visual outcomes, and also to identify any safety differences between the two drugs.
Visual Outcome Results: When comparing Lucentis monthly to Avastin monthly, the CATT study
demonstrated no difference between the two drugs, with patients in both groups gaining more than 8
letters on the eye chart on average over the course of a year. When comparing Lucentis as needed to Avastin as needed, the study was inconclusive. The study also demonstrated that Lucentis as needed produced results as good as Lucentis given monthly.
All four groups showed a reduction in the amount of fluid under or within the retina over the course of treatment. The Lucentis monthly group showed a greater reduction in fluid than any of the other three groups.
Safety Outcomes: The rate of ocular infection following injection of medication was similar with the two drugs and similar to the 1 in 2,000 rate that has been previously reported in large studies. The CATT study demonstrated similar rates of death, heart attack and stroke with the two medications, and slightly higher rate of serious disease events requiring hospitalization in the Avastin group. It is unclear whether the rates of these adverse events were significantly higher than in untreated patients with comparable medical risk factors.
I have wet AMD. What do the results of the CATT trial mean for me?
Across the United States for the past few years, retina specialists have been treating patients in almost equal numbers with Lucentis and Avastin for wet AMD depending on drug availability, insurance coverage, physician preference, and patient preference.
From an efficacy standpoint, the CATT trial demonstrated excellent visual outcomes in all four groups, with no statistically significant difference in the average visual improvement between groups. It is unclear whether Avastin as needed is equivalent or inferior to the other three groups. Lucentis monthly appeared to provide a greater reduction in fluid than any of the other three groups, but the visual significance of this outcome is unclear at the one year time point.
From a cost standpoint, Avastin is significantly less expensive than Lucentis. The average cost per year for medication alone was $23,400 in the Lucentis monthly group; $13,800 in the Lucentis as needed group; $595 in the Avastin monthly group; and $385 in the Avastin as needed group. The higher cost of Lucentis is borne by Medicare, individual patients, or a combination. Patient cost most often consists of a deductible or copay. Genentech's Access Solutions has previously provided free Lucentis to some patients who had no insurance. Independent non-profit financial and medication assistance organizations such as the Chronic Disease Fund can provide copay assistance to patients who cannot afford the copay for some medications and conditions including Lucentis for wet AMD.
From a safety standpoint, the rate of ocular complications was very low in all groups. With regard to non-ocular events, the CATT trial showed a higher rate of hospitalizations for serious illness in the groups receiving Avastin. These illnesses did not fall into a single category and it is unclear whether they are linked to the medication rather than co-existing medical conditions which are common in older patients. The complications most likely to be linked to Avastin or Lucentis, such as stroke and heart attack, were no different between groups in this study, but there were insufficient numbers of patients to answer these questions conclusively.
Ultimately, the decision to continue with Avastin or Lucentis versus changing medications based on the CATT study results will be different for every patient and his or her retina specialist, taking the above factors into consideration. Clinical studies rarely provide black and white answers to treatment questions. The data can be interpreted as a demonstration that Avastin is just as effective and safe as Lucentis at a fraction of the cost, or the data can be interpreted as a demonstration that Lucentis given monthly provides the best outcomes with a lower rate of adverse events than with Avastin treatment and therefore the higher cost is justified. In either case, the data suggested that patients with wet AMD and the physicians treating these patients have at least two good options in the treatment of a formerly blinding condition.
We anticipate much discussion of this topic in the coming months, and we expect that the two year results of the CATT study will clarify some of the findings mentioned above. We look forward to using this new information to continue providing our patients with the best possible care, taking into account all relevant factors such as efficacy, safety and cost.
