"You get what you get," Acorda Therapeutics Inc.'s chief technology officer, Richard Batycky, told BioWorld Today on the subject of the placebo effect in the successful phase III trial with inhaled levodopa CVT-301 for improving motor function in Parkinson's disease (PD) patients. "We hope that we – as we did – power the study enough to make sure that we make up for any increased noise."

Investor jitters over the pending outcomes for Ardsley, N.Y.-based Acorda's disputed intellectual property related to the multiple sclerosis therapy Ampyra (dalfampridine) probably kept shares from rising as much as they might have on word of the CVT-301 win, but shares (NASDAQ:ACOR) did gain ground, closing Thursday at $24.65, up $4.25, or 20.8 percent.

CVT-301 is being studied as a treatment for off periods (re-emergence of PD symptoms) in people taking an oral carbidopa/levodopa regimen. A total of 339 study participants were randomized and received at least one dose of CVT-301 or placebo, Acorda said, and participants self-administered treatment up to five times daily for 12 weeks. Called SPAN-PD, the phase III study met its primary endpoint of statistically significant improvement of motor function compared to placebo.

Raymond James analyst Christopher Raymond called the outcome "about what you would expect" and noted a "placebo response [that] appeared more robust" in the phase III experiment than in earlier research. Acorda plans to submit an NDA in the second quarter of this year, and included will be data from two long-term safety studies, due yet this quarter. "It's probably a bit of a stretch to talk about chronic delivery with only a three-month study, which is why we said we're going to wait until we also see the one-year" results, said Batycky, the site head for Acorda's Chelsea, Mass., location, where the work on CVT-301 has been centered.

SPAN-PD had three arms: CVT-301 84-mg and 60-mg doses (equivalent to 50-mg and 35-mg fine particle doses, respectively) and placebo. The primary endpoint of the study was the change at week 12 in Unified Parkinson's Disease Rating Scale-Part 3 (UPDRS III) score relative to 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 (p=0.009). Participants reporting serious adverse events were: three (2.7 percent) in the placebo arm, six (5.3 percent) in the 60-mg arm and two (1.8 percent) in the 84-mg arm. There was one death in the study, a suicide in the 60-mg group, judged by the investigator to be not related to study drug.

Batycky said Acorda has "shared [the data] with three key opinion leaders [KOLs] and they were not surprised that placebo [results] looked different" in phase III. "They've seen everything under the sun." The KOLs focused on whether CVT-301 could beat placebo, hit statistical significance and show clinically important upside. "We think we do have that," he said, adding that the company has "several orthogonal measures beyond UPDRS III that we feel will support the application," but those have not been disclosed yet. More data likely will roll out at the International Congress of Parkinson's Disease and Movement Disorders in Vancouver, British Columbia, in early June.

EASE-OF-USE BENEFIT AHEAD?

Regarding tolerability in the inhalation-naïve patients, Batycky was "pleasantly surprised. Some people don't like inhaling things, especially in this setting. Maybe that speaks more to the unmet need, as a PD patient might find themselves stuck in a chair for an hour or two" and having a therapy that "can get them moving again" is a motivator to inhale.

Analyst Raymond wrote that the patent ruling on Ampyra, meanwhile, "remains a giant elephant in the room," adding that his firm is "more comfortable on the sidelines" for now. J.P. Morgan analyst Cory Kasimov said "the best-case scenario is still in play as we await the decision on both the inter partes review and abbreviated NDA filers (expected in March and any day now, respectively)." He said in a report that "it will also be important to get a better appreciation for the overall clinical meaningfulness of the CVT-301 data following presentation at a medical meeting and KOL feedback. That said, we believe risk/reward for ACOR shares remains skewed to the upside on the heels of this latest development, and into the admittedly difficult-to-predict intellectual-property decisions."

RBC Capital Markets analyst Michael Yee said the "effect size [of the phase III trial] will be questioned, but it's enough to get approved, in our view," though like the others he cited the difference between SPAN-PD and the earlier experiment. "The company says some publications point to a 2.5 point [UPDRS III] change as minimally clinically significant, five points as moderate and 10-11 points as maximal," he wrote in a report, calling the phase III results therefore "a fundamental positive" and "important to securing some base-case floor valuation into the stock."

Leerink's Paul Matteis pointed to incidences of cough and upper respiratory tract infection that were higher in the phase III experiment, but said that, "from the top-line, we don't think any of this serves as an approvability issue, though we are highly interested in the 12-month safety data, as it may be of importance to labeling and ease of use for physicians. Today, we only know of two inhaled medicines for non-respiratory indications: Afrezza [insulin, Mannkind Corp.] and Adasuve [loxapine for acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults, Alexza Pharmaceuticals Inc.]. Both appear to have a more problematic respiratory safety profile than CVT-301, but of note [is that] both have a pulmonary function test requirement on their labels," he wrote in a report.

In the race to treat PD off episodes, Marlborough, Mass.-based Sunovion Pharmaceuticals Inc. last September agreed to pay $624 million cash for Cynapsus Therapeutics Inc., of Toronto, gaining sublingual APL-130277, an FDA fast-tracked form of apomorphine for which Cynapsus planned an NDA filing in the first half of this year. (See BioWorld Today, Sept. 2, 2016.)