Shire said today it will end its clinical program to expand the use of Vyvanse® (lisdexamfetamine dimesylate) Capsules (CII) into major depressive disorder (MDD), after the ADHD treatment failed two Phase III clinical trials assessing its efficacy and safety compared with placebo.
Instead, Shire said it will look to expand Vyvanse’s indication in binge eating disorder, another new indication for which the company plans to file for marketing approval with the FDA later this year, Shire CEO Flemming Ornskov, M.D., said in a statement.
The termination was the company’s second Phase III disappointment since December, when the company reported mixed results from its OPUS-2 Phase III trial for of its dry eye disease treatment lifitegrast. Last month, Philip J. Vickers, Ph.D., Shire’s head of global research and development, told GEN the company will await a planned consultation with the FDA before deciding whether and how to proceed with that clinical program.
No such reexamination will occur following the failed Vyvanse trials, which were designed to study whether the drug could sustain a new indication as an adjunctive treatment for MDD in adults who inadequately responded to antidepressant monotherapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI).
“We had seen the MDD program for Vyvanse as being risky and had not included any revenues from this indication in our base case or in the context of our innovation score for Shire. However, this failure does remove what could have been a meaningful source of upside for Shire (c.$1bn+ in peak sales opportunity),” Goldman Sachs concluded in a report coauthored by Keyur Parekh, Divya Harikesh, Steve Chesney, and Mick Readey.
But FBR & Co. took a more positive view. While also not including revenue for the indication, the firm noted that the program was a holdover from Dr. Ornskov’s predecessor as Shire CEO, Angus Russell.
“We suspect that investors had low expectations,” FBR said in a note coauthored by William Tanner, Ph.D., Fernando Bringas, and Matthew Lillis. “We are not making changes to our model, and we would be surprised if Street models change appreciably.”
A total 830 adults ages 18–65 participated in the two identically designed Phase III studies. The first study randomized 404 adults; the second, 426 adults. Both trials failed to meet their primary endpoint, defined as the change from augmentation baseline eight weeks into treatment to week 16 in Montgomery-Asberg Depression Rating Scale (MADRS) total score.
In the first study (SPD489-322), participants experienced a mean reduction of 6.1 in MADRS total score for Vyvanse compared with 6.3 for placebo. Augmentation baseline MADRS scores for Vyvanse and placebo groups were 25.4 and 25.2, respectively.
Three patients treated with Vyvanse and five placebo patients experienced serious adverse events, while eight patients on Vyvanse and seven on placebo had treatment-emergent adverse events (TEAEs) that led to the study being ended. Most commonly reported TEAEs among Vyvanse patients included insomnia, dry mouth, decreased appetite, headache, nausea, nasopharyngitis, and dizziness.
In the second study (SPD489-323), participants experienced a mean reduction of 7.3 in MADRS total score for Vyvanse compared with 6.8 for placebo. Augmentation baseline MADRS scores for Vyvanse and placebo groups were 26.0 and 25.7, respectively.
While one patient treated with Vyvanse and one patient treated with placebo experienced SAEs, two other Vyvanse patients and one placebo patient also had TEAEs leading to the study’s end that led to study discontinuation. Most commonly reported TEAEs for Vyvanse participants included headache, dry mouth, nasopharyngitis, decreased appetite, insomnia, hyperhidrosis, and restlessness.
Shire said further evaluation of the safety information related to vital signs, ECG, and clinical laboratory results and other safety assessments was already under way.