FDA again rejects Allergan's migraine treatment Semprana, expands approval for Ozurdex in diabetic macular oedema

Allergan said Monday that the FDA issued another complete response letter regarding its application to market the inhalable acute migraine therapy Semprana (dihydroergotamine), formerly known as Levadex, citing concerns about the drug's delivery device. Further, the drugmaker announced the expanded US approval of its intravitreal implant Ozurdex (dexamethasone) to treat certain patients with diabetic macular oedema (DME), and also provided a pipeline update with plans to advance its anti-VEGF DARPin (abicipar pegol) and bimatoprost eye treatments into Phase III testing.

Regarding the Semprana rejection, Allergan said the FDA acknowledged that the company had made improvements to the canister filling process cited in the previous complete response letter. However, the drugmaker said the latest issues relate to "specifications around content uniformity on the improved canister filling process and on standards for device actuation." Allergan noted that no safety or efficacy concerns were raised and that the agency had provided draft labeling for the product in June 2013.

The company further indicated plans to work with the FDA to "fully address" the concerns raised in the latest complete response letter, and now expects the next regulatory action will occur by the end of next year's second quarter. In 2012, the FDA rejected an application for the therapy by MAP Pharmaceuticals, prior to Allergan's acquisition of the company last year. Sterne Agee analyst Shibani Malhotra, who estimates Semprana could generate sales of $150 million in 2017 if approved, said US clearance could bolster Allergan's attempt to resist takeover efforts by Valeant Pharmaceuticals, but that the agency's refusal "may have the opposite effect."

Meanwhile, Allergan said the FDA's approval of Ozurdex expands the product's indication to include treatment of DME in adults who have an artificial lens implant or who are scheduled for cataract surgery. Scott Whitcup, chief scientific officer at Allergan, commented that the approval "further strengthens" the company's position in ophthalmology and in the retina subspecialty. The sustained-release steroid implant was already approved to treat adults with macular oedema following branch retinal vein occlusion or central retinal vein occlusion, and also for adults with non-infectious uveitis affecting the back segment of the eye.

With regard to its pipeline update, Allergan reported that the company completed a topline analysis of Phase II data for its anti-VEGF DARPin treatment in neovascular age-related macular degeneration and that it was progressing the therapy to late-stage development starting in the second quarter of 2015. Specifically, the analysis showed that mean visual acuity improvement from baseline at 16 weeks was 8.2 letters and 6.3 letters for the higher- and lower-dose DARPin groups, respectively, versus 5.3 letters for Roche and Novartis' Lucentis (ranibizumab). Further, after 20 weeks, the high- and low-dose DARPin arms achieved respective mean visual acuity improvements of 9.0 letters and 7.1 letters, versus 4.7 letters for the Lucentis group. Allergan noted that "although the study was not powered to show statistically significant differences between treatment groups…these data suggest that [the higher DARPin dose] is at least as effective as monthly [Lucentis], with a longer duration of action."

The company also disclosed plans to initiate Phase III trials of its bimatoprost sustained-release implant for the treatment of elevated intraocular pressure and glaucoma by the end of the year. Allergan said a review of mid-stage data suggests that the implant has efficacy comparable to the daily topical formulation of bimatoprost, with duration of four to six months. The company, which said it has shared the data with the FDA, indicated that the sustained-release implant has "the potential to change the treatment paradigm for patients who currently rely on daily topical eye drops to treat their condition."

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