2-Year CATT Results Show $50 Avastin Equivalent to $1,950 Lucentis
Avastin and Regeneron’s Eylea Could Squeeze Lucentis Out of Wet AMD
Novartis Could be Biggest Loser in Wet AMD Space on IVAN Results
Download Full 7-Page Note with Important Disclosures: Morning Note 05-01-12 ROG NVS REGN BAYN
The 2-Year results from the Comparison of Age-related Macular Degeneration Treatments Trials (CATT), which compared two of Roche/Genentech’s drugs, Avastin (bevacizumab) versus Lucentis (ranibizumab) for the treatment of Wet Age-Related Macular Degeneration (Wet AMD) were published in the journal Ophthalmology in the paper titled “Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration”. The U.S. National Institutes of Health National Eye Institute stated that the results showed that “Avastin and Lucentis are equivalent in treating age-related macular degeneration.”
Avastin is a full-length humanized monoclonal antibody that was FDA approved for the treatment of multiple solid tumor cancers in 2004 while Lucentis is a smaller molecule (antigen binding fragment) derived from the same murine monoclonal antibody that is used to construct Avastin. Lucentis was FDA approved for the treatment of “wet” or neovascular Age-Related Macular Degeneration (AMD) in 2006. The two drugs mechanisms of action are the same but they differ in size, affinity for VEGF, speed of clearance from the eye, and cost. Lucentis, which is FDA-approved for Wet AMD, costs approximately $1,950 per dose or $23,400 per year while Avastin, used off-label in Wet AMD, costs approximately $50 per dose or $600 per year.
Winners: We believe these results will split the market between Avastin for Medicare and other cost-sensitive patients, especially those that are able to receive treatment monthly, and Regeneron/Bayer’s Eylea (aflibercept) for private insurance and patients desiring treatment as needed.
Losers: We see Lucentis as less attractive versus Eylea since the latter is FDA approved for once every eight weeks ($1,850 per treatment) based on trials that showed it to be equivalent to monthly Lucentis and thus yielding a cost savings of $12,300 per year. While Roche/Genentech are expected to be impacted, we note that Novartis only has rights to Lucentis (ex-US) and not Avastin, resulting in Novartis losing the most opportunity in the cost restrained ex-US market. We further believe the upcoming 12-month results of the U.K. IVAN trial (also Avastin vs. Lucentis) puts Novartis at risk. (see IVAN trial at http://www.controlled-trials.com/ISRCTN92166560 )
NOTE: The CATT and IVAN results will be discussed in detail at The Association for Research in Vision and Ophthalmology (ARVO) conference on Sunday May 6th at 1:15pm.
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Avastin (bevacizumab) vs. Lucentis (ranibizumab) Monthly vs. PRN |
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Source: Martin D., et al, “Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration” Ophthalmology 4/31/12 |
Specifically, the results for the 1,107 patients who were followed up during year 2 (out of 1,185 patients originally enrolled) showed that:
1.) Ranibizumab and bevacizumab had similar effects on visual acuity over a 2-year period.
Mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P=0.21).
2.) Treatment as needed (PRN) resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment versus monthly treatments.
Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P= 0.046).
The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P=0.0003; regimen, P<0.0001).
Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P=0.03) and a lower proportion without fluid (-19%; P<0.0001).
3.) There were no differences between drugs in rates of death or arteriothrombotic events.
Rates of death and arteriothrombotic events were similar for both drugs (P>0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P=0.009).
4.) 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.
Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).
Among all organ systems, the greatest imbalance was in gastrointestinal disorders.
When all known VEGF–related serious adverse events are excluded, most of the imbalance remains, leaving it uncertain whether this difference was the result of chance, imbalances at baseline not captured in multivariate modeling, or truly higher risk.
We note these comments made at ARVO 2011: The excess number of events were distributed over many different types of conditions, most of which were not seen in cancer trials where patients had received 500X the Avastin dose that was used in the CATT trial. Based on this, Dr. Martin believed this difference may not be drug-related and that the trial would have required 10,000 patients to be powered to detect the differences to statistical significance.
The paper can be accessed at: http://www.ophsource.org/webfiles/images/journals/ophtha/announcement.pdf
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Adverse Events Within 2 Years of Enrollment |
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Source: Martin D., et al, “Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration” Ophthalmology 4/31/12 |
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Download Full 7-Page Note with Important Disclosures: Morning Note 05-01-12 ROG NVS REGN BAYN
