FDA delays diabetic macular edema insert approval

Alpharetta, GA-Alimera Sciences Inc. is preparing additional safety and efficacy data for the FDA on its investigational sustained drug-delivery system, fluocinolone acetonide intravitreal insert (Iluvien), a potential treatment for diabetic macular edema (DME).

In its letter, the FDA requested safety and efficacy data through month 36 of the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) study. The company had submitted data through month 24, but Myers said it has completed month 36 and is preparing the analyses. He said the data also would be presented Feb. 12 at the Angiogenesis, Exudation and Degeneration 2011 meeting at Bascom Palmer Eye Institute, University of Miami Miller School of Medicine.

"We're hopeful that, after gaining more clarity on Feb. 2, we can submit our amendment by the end of the first quarter, which will mean [we may] have approval in the third or fourth quarter," he said.

FDA spokeswoman Karen Riley said the CRL was not publicly available.

According to Myers, the FDA also questioned some of the manufacturing process specifications and noted deficiencies in current good manufacturing practices during its facility inspections in August and September of two of Alimera's third-party manufacturers. Myers said the manufacturers, Farmabios, in Italy, which makes the fluocinolone acetonide, and Alliance Medical Products, in Irvine, CA, which will handle the packaging, have a solid history with the FDA and are working to resolve the deficiencies.

Myers said he thinks the manufacturing issues can be resolved within 6 months and won't delay approval. "I'm not concerned that [these] issues in and of themselves will delay commercialization if in fact the FDA is comfortable with the clinical data," he said.

The drug delivery system includes an extended-release intravitreal insert designed to provide a therapeutic effect for up to 36 months by delivering sustained sub-microgram levels of fluocinolone acetonide. The insert is administered via a 25-gauge needle, which allows the wound to self-seal.

Baruch Kuppermann, MD, PhD, professor and chief of the Retina Service at University of California, Irvine, presented results of the phase III FAME clinical trials at the annual meeting of the American Academy of Ophthalmology. In trials involving 956 patients in the United States, Canada, Europe, and India, he said data showed a statistically significant difference in best-corrected visual acuity versus control by 3 weeks, and that difference was maintained through month 24. The 36-month data were completed later in October.

Alimera has licensed rights to the drug delivery technology from pSivida Corp. (Boston) and the companies are conducting phase II clinical trials of the system in wet age-related macular degeneration, dry age-related macular degeneration, and retinal vein occlusion. Myers said the CRL does not affect those trials, which will be complete later this year, and the company will determine whether to pursue phase III trials.

The technology holds promise as a novel treatment for DME, since the only existing FDA-approved treatment involves laser photocoagulation therapy, which can leave irreversible blind spots. Investors, who had hoped the FDA would issue an approvable letter by the end of 2010, were disappointed by the news that approval would be delayed. Alimera shares dropped from $11.22 on Dec. 23 to just under $10 by mid-January. Meanwhile, pSivida shares fell from $6.36 to just above $5 in the same period.

Citigroup and Oppenheimer analysts, who follow Alimera, lowered their price targets by $3 and $2 respectively, but both remained positive on the future of the drug delivery system. Citigroup analysts recommended investors buy shares, while those at Oppenheimer maintained their "outperform" rating.

Myers said he wasn't discouraged by the drop.

"We've lost no more than 10% of value since the CRL came out; that's more encouraging to me when you think a lot of companies lose a lot more value," he said. "I could have had a better Christmas present, but very rarely do these things go just as planned. I do remain very encouraged that [these] 3-year data will support this approval."