It’s hard to understand all of the drugs in development for mental disorders, but here are a few that we’ve been able to get a handle on that have been recently approved for prescription, or will likely be approved as a future medication. Some drugs are on the short-term horizon, while others are years away from making it to your pharmacist’s shelf.
Drugs for Depression
Although the Phase III pipeline of drugs for the treatment of depression is deep, including several compounds with new mechanisms of actions, none is expected to be approved in 2009. Pristiq (desvenlafaxine, the major metabolite of venlafaxine), Wyeth’s follow- up to Effexor (venlafaxine), was approved for depression in adults by the FDA in March and could gain ground in the clinic next year.
AstraZeneca submitted an sNDA in May for Seroquel XR for the treatment of generalized anxiety disorder, which was the first submission of an atypical antipsychotic medication for this indication. In February, the company submitted an sNDA for Seroquel XR for the treatment of depression.
In September, LaboPharm submitted an NDA for DDS-04A for the treatment of depression. This compound is the well-known antidepressant trazodone a 5-HT2 receptor antagonist, formulated for once-daily administration. The NDA was based on data from five pharmacokinetic studies and a North American study that included more than 400 patients.
New drugs on the horizon for late 2009/2010 U.S. approval include Valdoxan (agomelatine), which is in development by Novartis and Servier, and Saredutant (SR 48968), a Sanofi-Aventis compound. Valdoxan, which has a novel mechanism of action—melatonin (MT1 and MT2) receptor agonist and 5-HT2C receptor antagonist—and an attractive side-effects profile (i.e., no sexual dysfunction or weight gain), is anticipated.
Novartis is currently conducting four large-scale Phase III trials in the United States, all of which are scheduled to complete in 2009. A U.S. NDA might be submitted in 2009. Saredutant, a neurokinin-2 (NK2) receptor blocker, is well tolerated but has produced mixed results in long-term Phase III trials. Sanofi-Aventis will decide on regulatory submissions based on the results of two ongoing trials assessing saredutant in combination with escitalopram and paroxetine, which are scheduled for completion in the first half of 2009.
Drugs for Bipolar Disorder
Longer-acting injectable and oral formulations of approved atypical antipsychotic medications are the focus of late-stage drug development for bipolar disorder.
Janssen is currently marketing Risperdal Consta, a long-acting, injectable formulation of risperidone for the treatment of schizophrenia. The drug was developed by combining risperidone with the Alkermes’ Medisorb delivery system to maintain a therapeutic drug concentration when administered once every two weeks.
In 2008, Janssen submitted two supplemental New Drug Applications (sNDA) for bipolar indications. An sNDA submitted in April seeks approval for adjunctive maintenance treatment to delay the occurrence of mood episodes in patients with frequently relapsing bipolar disorder. A July sNDA submission looks to indicate Risperdal Consta as monotherapy for the maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in adults.
Another long-acting atypical antipsychotic, AstraZeneca’s Seroquel XR (quetiapine extended-release tablets), was approved in October 2008 for acute treatment of depressive episodes associated with bipolar disorder and manic and mixed episodes associated with bipolar I disorder, as well as maintenance treatment of bipolar I disorder as adjunctive therapy to lithium or divalproex.
Drugs for Schizophrenia
Late-stage drug development for schizophrenia includes a new injectable formulation of an approved atypical antipsychotic and two new drug candidates with atypical antipsychotic mechanisms of action.
Janssen developed an injectable formulation of its antipsychotic, Invega (paliperidone extended-release) by combining it with Elan’s NanoCrystal technology to enable administration by intramuscular injection on a once-monthly schedule. In October 2007, the company submitted an NDA for the treatment of schizophrenia and prevention of symptom recurrence. In August 2008, the FDA requested additional data before approving the NDA, but did not require any additional studies. Janssen is currently evaluating the FDA response and will work with the agency to resolve outstanding questions. Potential advantages of Invega over Risperdal Consta include reduced dosing frequency (once monthly vs. once every two weeks) and no need for refrigeration.
In September, Lundbeck’s NDA submission seeking approval for Serdolect (sertindole) for the treatment of schizophrenia was accepted for review by the FDA. Serdolect is a new-generation atypical antipsychotic. It exhibits a higher level of limbic-selective increased dopaminergic activity than other atypical agents, which may contribute to an attractive extrapyramidal side-effect profile. Serdolect has been launched in Europe, South and Central America, Asia and the Middle East and has been administered to more than 70,000 patients.
Schering-Plough’s NDA submission for its new 5-HT2A- and D2 receptor antagonist Saphris (asenapine) was accepted by the FDA in November 2007 and is undergoing a standard review. Saphris is a fast-dissolving, sublingual tablet acquired by Schering-Plough when it combined with Organon BioSciences earlier in November 2007. The NDA seeks approval for schizophrenia and acute or mixed episodes associated with bipolar I disorder. In November 2008, top-line Phase III clinical trial results demonstrated the efficacy of Saphris in long-term schizophrenia relapse prevention. Approval and launch in 2009 are possible.
Drugs for Attention Deficit Disorder (ADHD)
A new drug with a nonstimulant mechanism of action may be approved in 2009 for the treatment of attention-deficit/hyperactivity disorder (ADHD). Intuniv (guanfacine extended-release tablets) is a selective alpha2A-agonist in development by Shire for the once-daily treatment of ADHD. The company submitted an NDA for monotherapy for the treatment of ADHD symptoms throughout the day in children aged 6 to 17 years and received an approvable letter from the FDA in June 2007. The FDA requested additional information, and the company has been conducting additional clinical work related to the drug’s label.
Immediate-release guanfacine, a medication used to treat high blood pressure, also is used off-label in ADHD.
Anticipated advantages of Intuniv over guanfacine include FDA approval specifically for ADHD and maintenance of blood concentration in the therapeutic range, which is problematic with immediate-release formulations. Another potential advantage: Intuniv is not a controlled substance, and is not associated with any known mechanisms for potential abuse or dependence.
An estimated 30% of children with ADHD cannot tolerate stimulant drugs or do not benefit from currently available ADHD medications. Intuniv also might have applications in combination with stimulant drugs to reduce aggression and insomnia associated with stimulants and adult patients. Shire hopes to gain FDA approval and launch Intuniv in the second half of 2009.