HAMBURG, Germany — Lampalizumab (Genentech), also known as anti-factor D, appears to be safe and effective for patients with age-related macular degeneration, results of the MAHALO trial show.
"This is the first positive treatment result for patients with dry age-related macular degeneration and geographic atrophy," Frank Holz, MD, from the University of Bonn in Germany, told Medscape Medical News.
Lampalizumab reduced the atrophy area at 18 months. Before this study, lampalizumab had never been injected into the vitreous body in humans.
Dr. Holz presented the phase 2 MAHALO study results here at the 13th EURETINA Congress.
Lampalizumab is a new monoclonal antibody that inhibits complement factor D, which is a rate-limiting enzyme of the alternative complement pathway. Increased activation of this pathway, which is a component of the immune system's defense against infections, is associated with the development of macular degeneration.
The development of effective agents for this patient population is important because there are no approved treatments, and currently the outlook for such patients is "dismal," Dr. Holz explained.
The researchers enrolled 129 patients with bilateral geographic atrophy recruited from multiple sites in the United States and Germany to assess the safety, tolerability, and activity of lampalizumab.
Participants, who were 60 to 89 years of age, were randomized to lampalizumab 10 mg or sham injections.
Table. Distribution of Patients in the 4 Treatment Groups
|Treatment Interval||Lampalizumab, n||Sham, n|
|Every other month||44||21|
The researchers pooled data from the 2 sham groups for the analyses.
The primary efficacy end point was mean change in geographic atrophy area over 18 months assessed with fundus autofluorescence. The secondary outcome was the same change assessed with color fundus photographs.
"A positive treatment effect was seen in the monthly lampalizumab group beginning at month 6, and was maintained through month 18 with primary and secondary imaging end points," Dr. Holz reported.
In a subgroup analysis of monthly lampalizumab, the overall reduction in geographic atrophy area in patients with a specific set of experimental biomarkers was more than double that of the study cohort as a whole (44.0% vs 20.4%). This improvement from baseline to 18 months was statistically significant (P < .005).
In this subgroup analysis, 57% of the patients tested positive for these biomarkers. The identity of the biomarkers will be revealed at a future meeting, Dr. Holz said.
Although eye pain and conjunctival hemorrhage were the most common adverse events associated with intravitreal injection, "there was no drug-associated adverse-event signal here," Dr. Holz noted. No cases of endophthalmitis were reported, for example, and intraocular inflammation and intraocular pressure elevation rates were consistent with those seen with ranibizumab (Lucentis, Genentech, Novartis) in the treatment of wet macular degeneration, he added.
"This study seems to be very interesting." However, "monthly injections give results by half a year. This is a problem — I am really not sure what is happening [during that time]," said session moderator Sebastian Wolf, MD, PhD, from the Inselspital, University of Bern in Switzerland.
He questioned the utility of a monthly injection regimen "that reduces the rate a little bit," and added that "the ultimate goal is a drug that stops progression completely."
The efficacy finding starts at 6 months because "the measurement was not done earlier," Dr. Holz told Medscape Medical News. "But you would not expect to see an immediate response. This is a slowly evolving disease." Dry macular degeneration is not the same as neovascular or wet macular degeneration, he added, where one often sees an immediate treatment response.
In response to a comment during the question and answer session that the treatment is not curative, Dr. Holz acknowledged that this is "obviously not a healing treatment. Atrophy, once it starts, continues to grow. It is not confined to the macula or the posterior pole, so it makes sense to try to slow down the progression." If phase 3 trials confirm these results, he added, lampalizumab might extend the preservation of the fovea for several years, which would be clinically relevant to the patient.
There were some dropouts and discontinuations for various reasons, such as hemorrhage and conversion to neovascular or wet macular degeneration. At 18 months, however, 90% of patients chose to move to an open-label extension study.
This study was funded by Genentech. Dr. Holz reports financial relationships with Genentech, Bayer, Merck, Novartis, Optos, and Roche. Dr. Wolf reports financial relationships with Novartis, Molecular Partners, Allergan, and Bayer.
13th EURETINA Congress. Presented September 27, 2013.
Medscape Medical News © 2013 WebMD, LLC
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Cite this: Lampalizumab Appears Safe for Dry Macular Degeneration - Medscape - Sep 30, 2013.