Allergan plc. and Gedeon Richter plc. announced positive topline results for RGH-MD-53, a Phase 3 study of cariprazine for the treatment of adults with major depressive episodes associated with bipolar I disorder (bipolar I depression). The companies announced in December 2017 positive topline results for the second pivotal trial (RGH-MD-54) of cariprazine in the treatment of bipolar I depression. In that trial both cariprazine 1.5mg and 3mg were statistically greater than placebo.
The efficacy of cariprazine in the treatment of bipolar I depression has been demonstrated in three positive pivotal trials, including RGH-MD-53, RGH-MD-54 and RGH-MD-56. Allergan plans to include data from all three pivotal trials in the Company’s Supplemental New Drug Application (sNDA) to the FDA in the second half of 2018.
Cariprazine is currently approved in the U.S. under the brand name Vraylar for the treatment of schizophrenia in adults, and acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
“We are very pleased with the results of our third pivotal study, which reinforce the wealth of data supporting cariprazine as a potential treatment in adults with bipolar depression” said David Nicholson, chief research & development officer at Allergan. “Bipolar depression is often difficult to treat and can be extremely debilitating for patients. At Allergan, we are committed to developing treatments that address unmet needs facing people living with mental illness and are looking forward to submitting an sNDA for cariprazine for patients suffering with bipolar I depression.”
For RGH-MD-53, the primary and key secondary efficacy endpoints were met for the cariprazine 1.5 mg dose group. Cariprazine 1.5 mg showed a significantly greater improvement than placebo for the change from baseline to week 6 on both the primary efficacy parameter the Montgomery-Asberg Depression Rating Scale (MADRS) total score (p=0.0417, LSMD -2.5), as well as the key secondary parameter, Clinical Global Impression Scale-Severity (CGI-S) (p=0.0417, LSMD -0.3). Cariprazine 3 mg showed a numerical improvement over placebo for both the primary (p=0.1051, LSMD -1.8) and secondary parameters (p=0.1370, LSMD -0.2), but did not reach statistical significance.
“Treating bipolar depression can be very difficult given the few therapies available to manage these symptoms of bipolar I disorder. Further, there are a limited number of products available to help treat the full range of bipolar disorder—from mania through depression,” said Gary Sachs, MD, associate clinical professor of Psychiatry at Harvard Medical School. “This data is encouraging for patients and the broader psychiatry community, as it demonstrates cariprazine’s potential in treating the full spectrum of the disorder.”
In this study, 493 patients were randomized (1:1:1) to placebo, cariprazine 1.5 mg and cariprazine three mg treatment groups to evaluate the efficacy, safety and tolerability of cariprazine in patients with bipolar I depression. Cariprazine was generally well tolerated in the trial. The overall incidence of patients who experienced adverse events was 51 percent for the cariprazine 1.5 and three mg dose groups, and 46 percent for the placebo group.
The majority of adverse events were mild to moderate and led to discontinuation in approximately 5 percent of cariprazine treated patients versus three percent of placebo treated patients. The most commonly reported adverse events in the cariprazine groups were akathisia, restlessness, nausea, and fatigue.
“Today’s positive results provide further support for the therapeutic value of cariprazine, one of our flagship products. We are encouraged by the findings, which mark a major step forward in making this promising treatment option available for patients suffering from bipolar depression,” added Dr. István Greiner, research director of Gedeon Richter Plc.
(Source: Allergan plc.)
Filed Under: Drug Discovery