Acorda Therapeutics said today it will work to address FDA concerns that prompted the agency to send a “Refuse to File” (RTF) letter in response to the company’s New Drug Application (NDA) for Parkinson’s disease (PD) treatment Inbrija (CVT-301).

Inbrija is a self-administered, inhaled formulation of levodopa (L-dopa) indicated for treatment of OFF periods (periods of worsening symptoms during therapy) in people with PD who are taking a carbidopa/levodopa regimen.

According to Acorda, the FDA determined after a preliminary review that the company’s NDA, submitted June 26, 2017, was not sufficiently complete to permit a substantive review.

The FDA cited two reasons for issuing its RTF, Acorda stated: The agency didn’t know when the manufacturing site would be ready for inspection, and had an additional unspecified question about the submission of the drug master production record: “The FDA also requested additional information at resubmission, which was not part of the basis for the RTF.”

Acorda responded by stating that it would pursue immediate guidance from the FDA, including a Type A meeting, to respond to the agency’s concerns, which the company said it believed were addressable, as well as clarify what if any additional information is required. The FDA has not requested or recommended additional clinical efficacy or safety studies, Acorda added.

“We will work with the FDA as quickly as possible to address the open issues and to clarify the path to successfully refile our application,” stated Ron Cohen, M.D., Acorda's president and CEO. “We remain confident in Inbrija’s data package and its promise as an important new therapy for people with PD. We see tremendous long-term value in its solid clinical profile, significant commercial opportunity, and strong IP, and we remain focused on working to bring patients this important new therapy.”

In February, Acorda trumpeted positive Phase III data for Inbrija, saying that the PD candidate—which applies Acorda’s ARCUS® drug delivery technology—showed a statistically significant improvement in motor function in people with PD experiencing OFF periods.

The trial assessed the safety and efficacy of CVT-301 in 339 participants who received the drug or placebo. The primary endpoint was the change at Week 12 in Unified Parkinson’s Disease Rating Scale-Part 3 (UPDRS III) score compared with placebo at 30 minutes post-treatment for the 84-mg dose. UPDRS III change for the 84-mg dose was –9.83, compared to –5.91 for placebo.

Just last month, Acorda said it was well underway with commercial preparations for the launch of Inbrija, and was expecting to submit a Marketing Authorization Application to the European Medicines Agency by the end of 2017.

Second Key Setback in 2017

The FDA’s rebuff is the second significant setback for Acorda this year. On March 31, a federal judge invalidated four of the five patents protecting the company’s top-selling drug, the multiple sclerosis (MS) treatment Ampyra® (dalfampridine). Acorda responded with a restructuring in which it eliminated 20% of its workforce.

Judge Leonard Stark of the U.S. District Court for the District of Delaware invalidated U.S. Patent Nos. 8,663,685, 8,007,826, 8,440,703, and 8,354,437 covering Ampyra. He sided with companies seeking to market generic versions of the MS drug—including Mylan, Roxane Laboratories, and Teva Pharmaceutical Industries—which argued that the Acorda patents were invalid due to obviousness.

At the time, Dr. Cohen said the restructuring would enable Acorda to focus on developing Inbrija—as well as tozadenant, an oral adenosine A2a-receptor antagonist also in Phase III development as an adjunctive treatment to levodopa in PD patients to reduce OFF periods.

Acorda expects to release Phase III data on tozadenant in the first quarter of 2018, the company said in announcing second-quarter results on July 27.

Acorda acquired worldwide rights tozadenant when it bought Biotie Therapies in a deal completed September 30, 2016, for $376 million.

Acorda’s troubles have prompted Scopia Capital Management, a New York hedge fund that owns 17% (approximately 7.7 million shares) of the company’s outstanding shares, to urge Acorda’s board to sell the company. Scopia says recent acquisitions such as Sunovion’s $624 million purchase of Cynapsus Therapeutics last year and Mitsubishi Tanabe’s $1.1 billion purchase of NeuroDerm last month “speak to the strategic value of late stage assets in PD.”

“Acorda is a more valuable acquisition candidate than either of these companies,” Scopia asserted in an August 7 letter. “A larger acquirer will not be burdened by the risks facing a standalone Acorda, and would be able to leverage the assets through greater scale.”

“Had the Company prevailed in the Ampyra litigation, Acorda would have been a unique company with a path to $1B in revenues and significant standalone value. Unfortunately, the Company was unsuccessful, and it has now crossed the Rubicon,” Scopia added. “In 2018 the business will revert to burning cash with a levered balance sheet and no clear timeline to return to profitability. These are treacherous waters.”

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