An old standby steps back to the plate as a new entry is abandoned amidst disappointing trials, devastating its maker’s stock value.
Both years in development, Alcobra’s Metadoxine Extended Release and Shire’s SHP465 have disappointed to different degrees throughout their development. This week, the makers of each drug received very different news about the future of their candidate attention deficit/hyperactivity disorder (ADHD) drugs.
Metadoxine Extended Release, or MDX, will no longer be tested after disappointing results in a phase 3 trial, the company reported today. The drug was intended as a treatment for ADHD and Fragile X Syndrome.
The primary endpoint for the MEASURE study, as it was called, was improvement over baseline in the Conners’ Adult ADHD Rating Scales (CAARS). In the trial, MDX did not achieve any statistically significant gains over placebo.
Yaron Daniely, PhD, CEO of the small Israeli drug maker, described the company as “extremely disappointed” with the top-line results. In September of 2016, the US Food and Drug Administration (FDA) placed a full clinical hold on the trials, citing what they called “adverse neurological findings,” though early phase trials seemed to indicate difficulty proving efficacy as opposed to major negative side effects.
The drug has yet to shine in tests of its other studied application, as a treatment for Fragile X syndrome, a genetic condition responsible for mental disabilities. Despite announcing that its results were not statistically significant for primary endpoints in a phase 2 trial in June of 2015, the FDA granted it a fast-track designation for that condition that September. Still, after today’s news, it’s speculated that Alcobra will continue to explore the application of MDX in Fragile X and other conditions.
The cancellation of testing for ADHD applications comes a week after the company negotiated with the FDA to reduce the constraints of the clinical hold, and had proposed to conduct a six-month phase 1 animal trial to assess MDX's safety. The FDA was considering that offer.
Metadoxine, MDX’s active ingredient, has shown efficacy in the treatment of acute alcohol intoxication and management of alcoholism.
The disappointing phase 3 results were announced earlier today in a press release, and the company’s plans to move on from testing the drug for ADHD were confirmed later in a conference call, as reported by Reuters. The immediate aftermath has devastated Alcobra’s stock value.
Shire Pharmaceuticals, meanwhile, announced recently that the FDA had again received their New Drug Application for SHP465. The drug is seen as somewhat of a sequel to Shire’s Adderall XR, the extended release version of their wildly successful and controversial Adderall, widely prescribed but often misused off-label. With the same active ingredient, amphetamine salts, SHP465 is designed to last for 16 hours, up from the XR version’s 12.
Shire’s efforts to develop the drug to approval are far from new. A version of it, then called SPD465, was first submitted to the FDA in 2006. Since then, the FDA has repeatedly requested more data, and Shire lost patented exclusivity for both the original Immediate Release and the XR version of Adderall.
The company at one point believed it was on pace to release SHP465 in 2015, but the day never came to pass. This week’s press release announces that “Shire resubmitted the NDA for SHP465 in response to the Approvable Letter from the FDA (May 18, 2007) that requested additional clinical studies and classified the response as a Class 2 resubmission with a review goal of six months.”
The recurring regulatory delays and requests have led to an accumulation of data. The submitted NDA contains results of 16 clinical studies evaluating the drug in over 1,600 patients, including one that tested the drug’s safety in 6-to-17 year olds for the treatment of pediatric ADHD. The company is confident in its performance over placebo in phase 3 studies, while acknowledging that those studies displayed many of the same common side effects of its chemical predecessors.
The FDA’s ruling on the drug is expected sometime in June 2017, according to the press release.