Date: 2016-08-08
Type of information: Granting of a patent
Product name: Aristada™ (ALKS 9070)
Compound: aripiprazole lauroxil
Therapeutic area: CNS diseases - Mental diseases
Action mechanism: Aristada™ (aripiprazole lauroxil) is an injectable atypical antipsychotic with one-month and two-month formulations in development for the treatment of schizophrenia. Once in the body, aripiprazole lauroxil converts to aripiprazole, which is commercially available under the name ABILIFY®. As a long-acting investigational medication based on Alkermes’ proprietary LinkeRx® technology, aripiprazole lauroxil is designed to have multiple dosing options and to be administered in a ready-to-use, pre-filled product format.
Company: Alkermes (Ireland)
Disease: schizophrenia
Latest news: * On February 25, 2016, Alkermes announced positive topline data from a randomized, open-label, pharmacokinetic study evaluating a two-month dosing interval of Aristada® (aripiprazole lauroxil) extended-release injectable suspension for the treatment of schizophrenia. Results from the study showed that the 1064 mg dose of Aristada® achieved therapeutically relevant plasma concentrations of aripiprazole with a PK profile that supports dosing once every two months. The most common adverse events for the two-month dosing interval were injection site pain and dyskinesia. Based on these results, Alkermes plans to submit a supplemental New Drug Application (sNDA) to the FDA in the second half of 2016. * On October 5, 2015, the FDA approved Aristada™ (aripiprazole lauroxil) extended release injection to treat adults with schizophrenia. Aristada™ is administered by a health care professional every four to six weeks using an injection in the arm or buttocks. The efficacy of Aristada™ was demonstrated in part by a 12-week clinical trial in 622 participants. In participants with acute schizophrenia who had been stabilized with oral aripiprazole, Aristada™ was found to maintain the treatment effect compared to a placebo. Data from that trial showed that multiple dose strengths of Aristada™ met the primary endpoint with statistically significant and clinically meaningful reductions in Positive and Negative Syndrome Scale (PANSS) total scores at Week 12, met the key secondary endpoint and demonstrated significant improvements in schizophrenia symptoms versus placebo. The most common adverse events in the study were insomnia, akathisia and headache. The results of the phase 3 study were published in June 2015 by The Journal of Clinical Psychiatry (see below). Aristada™ and other atypical antipsychotic drugs used to treat schizophrenia have a Boxed Warning alerting health care professionals about an increased risk of death associated with the off-label use of these drugs to treat behavioral problems in older people with dementia-related psychosis. No drug in this class is approved to treat patients with dementia-related psychosis. Aristada™ must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. The most common side effect reported by participants receiving Aristada™ in clinical trials was feeling the urge to move constantly (akathisia). * On August 21, 2015, Alkermes announced that the FDA has advised Alkermes that it will not be able to complete its review of the New Drug Application (NDA) for Aristada™ (aripiprazole lauroxil) for the treatment of schizophrenia by the Prescription Drug User Fee Act (PDUFA) action date of Aug. 22, 2015 . The FDA indicated that this delay was expected to be brief, measured in terms of weeks, but could not confirm specific timing. The FDA also indicated that no additional data or information is required from Alkermes at this time. * On October 22, 2014, Alkermes announced that the FDA has accepted for filing the New Drug Application (NDA) for aripiprazole lauroxil, the company’s investigational, novel, once-monthly injectable atypical antipsychotic for the treatment of schizophrenia. Under the Prescription Drug User Fee Act (PDUFA), the FDA’s target action date for the aripiprazole lauroxil NDA is Aug. 22, 2015. The NDA filing included the positive results from the pivotal phase 3 study assessing the efficacy and safety of aripiprazole lauroxil, in which aripiprazole lauroxil demonstrated significant improvements in schizophrenia symptoms, compared to placebo. In the randomized, multicenter, double-blind, placebo-controlled study, both doses of aripiprazole lauroxil tested, 441 mg and 882 mg administered once monthly, met the primary endpoint with statistically significant and clinically meaningful reductions in Positive and Negative Syndrome Scale (PANSS) scores, met all secondary endpoints and demonstrated significant improvements in schizophrenia symptoms versus placebo. Aripiprazole lauroxil was generally well tolerated in the study, and the observed safety profile of aripiprazole lauroxil was similar to that reported with oral aripiprazole. The most common adverse events in the study were insomnia, akathisia and headache. * On August 25, 2014, Alkermes announced that it has submitted a New Drug Application (NDA) to the FDA for approval of aripiprazole lauroxil, the company’s investigational, novel, once-monthly, long-acting injectable atypical antipsychotic for the treatment of schizophrenia. The data submitted as part of this NDA include the positive results from the pivotal phase 3 study assessing the efficacy and safety of aripiprazole lauroxil, in which aripiprazole lauroxil demonstrated significant improvements in schizophrenia symptoms, compared to placebo. The NDA submission follows the completion of the randomized, multicenter, double-blind, placebo-controlled, phase 3 study, in which both doses of aripiprazole lauroxil tested, 441 mg and 882 mg administered once monthly, met the primary endpoint with statistically significant and clinically meaningful reductions in Positive and Negative Syndrome Scale (PANSS) scores, met all secondary endpoints and demonstrated significant improvements in schizophrenia symptoms versus placebo. Aripiprazole lauroxil was generally well tolerated in the study, and the observed safety profile of aripiprazole lauroxil was similar to that reported with oral aripiprazole. The most common adverse events in the study were insomnia, akathisia and headache.
Patents: * On August 8, 2016, Alkermes announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. Patent Application 14/663,042 related to Aristada®, with allowed claims that will cover methods of treatment for schizophrenia. Alkermes expects this patent to issue within the next few months and expire no earlier than March 2035 . * On July 9, 2014, Alkermes announced that the United States Patent and Trademark Office (USPTO) has issued Notices of Allowance for aripiprazole lauroxil. The Notice of Allowance for U.S. Patent Application 13/607,066 is entitled "Heterocyclic Compounds for the Treatment of Neurological and Psychological Disorders." The allowed claims will cover methods of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a broad class of compounds, including aripiprazole lauroxil, Alkermes' long-acting injectable antipsychotic agent designed to provide patients with once-monthly dosing of a medication that, once in the body, converts to aripiprazole. Alkermes expects this patent to issue within the next few months and expire no earlier than September 2030. * On January 3, 2013, Alkermes has announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. Patent Application 12/823,007, titled "Heterocyclic Compounds for the Treatment of Neurological and Psychological Disorders." The allowed claims will cover a class of compounds that includes aripiprazole lauroxil, a proprietary Alkermes molecule formerly referred to as ALKS 9070, which is in development for the treatment of schizophrenia. Aripiprazole lauroxil is designed to provide patients with once-monthly dosing of a medication that, once in the body, converts into aripiprazole, a molecule that is commercially available under the name Abilify® for the treatment of a number of central nervous system (CNS) disorders.
Given this action, Alkermes expects the patent to issue within the next month and provide a patent term that would expire no earlier than 2030. A Notice of Allowance is issued after the USPTO makes a determination that a patent can be granted from an application.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2015-10-05
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news: * On August 8, 2016, Alkermes announced that it has submitted a supplemental New Drug Application (sNDA) to the FDA for a two-month dosing interval of Aristada® (aripiprazole lauroxil) extended-release injectable suspension for the treatment of schizophrenia. This potential new two-month offering would expand the range of Aristada® dosing intervals to include a third option for patients with schizophrenia.
The sNDA for Aristada® is based on the positive results from a recent randomized, open-label trial that assessed the pharmacokinetics (PK), safety and tolerability of Aristada® when administered at the investigational two-month interval and at the FDA -approved dosing intervals of once monthly and once every six weeks. A total of 140 patients with stable schizophrenia were randomized to receive either 441 mg Aristada® once per month, 882 mg Aristada® every six weeks or 1064 mg Aristada® every two months. Results from the study showed that the 1064 mg dose of Aristada® achieved therapeutically relevant plasma concentrations of aripiprazole with a PK profile that supports dosing once every two months. The most common adverse event for the two-month dosing interval was injection site pain.
