AMD Update 24: DARPins Phase 2 Trial Results Fall Short

Back in February, I first reported on Allergan’s DARPins in my Update 23: DARPins, The Next “Game Changer” for Wet AMD? In that report, I wrote that Molecular Partners’ MPO112 (Allergan’s AGN-150998) showed promise of improving vision and having a long ocular half-life which appeared to be a vast improvement over both Lucentis and Eylea, perhaps requiring injections every 3-4 months compared to bi-monthly for Eylea and monthly for Lucentis and Avastin. (I also noted a second agreement with Molecular Partners, the licensors of the DARPin technology to Allergan, in which a combination dual action anti-VEGF/PDGF drug therapy was also under investigation.)

Well, the first part of the promise, the longer interval injection rate for the DARPins, has fallen through. As reported by two analyst groups, Allergan presented results last Friday (November 15th) from the Phase 2 trial of AGN-150998 (anti-VEGF DARPin program) in wet AMD at the Retina Subspecialty Meeting ahead of the start AAO annual conference in New Orleans. The results supported the company's decision several months ago, to slow down advancement of the clinical trial, in that the drug failed to meaningful delay the time to retreatment and the associated rates of inflammation were higher than were anticipated. Though Allergan continues to evaluate the drug and still may ultimately advance it into Phase 3 studies, there appears to be only limited competitive threat to Eylea (or, perhaps Fovista, Ophthotech’s combination anti-VEGF/PDGF drug in clinical study – see my two write ups on Fovista, shown below, for more information about this potential drug). Specifically, the analysts see a low likelihood of commercial adoption or integration into the treatment paradigm for wet AMD without any sustained improvement in visual acuity or meaningful delay in the time to retreatment.

In looking at the data presented, the study evaluated two doses of the AGN-150998 (3mg and 4.2mg) vs. Lucentis. The drug was administered at week 4 and then pro re nata (PRN) or by week 16, and then again PRN or by week 32 at the latest. At day 60 and day 90, the 4.2mg dose appeared to delay the need for retreatment in ~10-15% of patients. Looking at the data another way, the 4.2mg dose appeared to delay the median time to retreatment by ~20 days. There were no differences in the percent of patients gaining 15 or more letters in best corrected visual acuity (BCVA) from baseline by week 16, and again at week 32.

In terms of safety, the AGN-150998 treatment was associated with a meaningful rate of ocular inflammation adverse events relative to Lucentis (13% vs. 0%). Specifically, treatment with AGN-150998 had higher rates of uveitis (3% with 3mg, 6% with 4.2mg, 0% with Lucentis), anterior chamber inflammation (2% and 3% vs. 0%), vitritis (7% and 2% vs. 0%).  For reference purposes, historical data imply the rate of intraocular inflammation in AMD trial are 13% and 1% with Lucentis and Eylea, respectively.

Allergan has indicated that it would be making changes to the manufacturing process to hopefully reduce the inflammation seen in the Phase 2 trials, when and if they decide to proceed to a Phase 3 trial.

I was not able to determine if Allergan and Molecular Partners still plan to go ahead with a clinical trial for the dual action drug, which remains in a pre-clinical stage.

References:

Analyst Reports - Private correspondence.

Fovista Reports:

AMD Update 19: Combination Therapy May Be A “Game Changer” for Wet AMD, Irv Arons’ Journal, June 4, 2012

AMD Update 20: How Fovista Works to Increase Vision in the Treatment of Wet AMD, Irv Arons’ Journal, June 28, 2012