The Food and Drug Administration (FDA) fast-track programs function to expedite drug development intending to treat fast-progressing illnesses that lack effective pharmacotherapies. Elan Corporation PLC, licensing partner of Transition Therapeutics Inc., was granted Fast Track Designation to the development program of the Alzheimer’s (AD) drug, ELND005 in July.
ELND005 is an orally bioavailable molecule that has been suggested to decrease β-amyloid accumulation and brain myo-inositol levels, which are both elevated in AD. The fast-track proposal was submitted because of ELND005’s ability to alleviate neuropsychiatric symptoms, which occur in 90 percent of AD patients.
“The drug was capable of reducing brain myo-inositol levels by 45 percent in AD patients who received 18-month treatment in phase 2 clinical trials,” Tony Cruz, Ph.D., CEO of Transition Therapeutics Inc. told Psychiatric News. He further explained that myo-inositol levels are associated with mood changes in bipolar patients and give rise to the agitation and aggression behavior exhibited by AD patients. “If you decrease myo-inositol levels, you’ll reduce mood changes. We noticed a reduction in psychiatric events in AD patients [administered ELND005],” said Cruz.
When asked if the ELND005 will be the game changer for treating AD, he replied, “Data support trends that reduces the regression of the cognitive function…but at the moment we are focusing primarily on neuropsychiatric events.”
Agitation and aggression are the most common neuropsychiatric symptoms in AD. The disruptive disorders contribute greatly to morbidity among patients while increasing caregiver burden. There are no FDA-approved medications that address this issue in AD patients.
A black-box warning has been added to mefloquine hydrochloride, a drug used to treat malaria. According to the FDA, the label has been changed due to increased risk for serious psychiatric and neurological side effects, including anxiety, paranoia, depression, hallucinations, and loss of balance. Side effects could last for years or be permanent, even after discontinued use.
The FDA suggests that patients, caregivers, and health care professionals should watch for these side effects. Mefloquine should be attenuated and substituted with alternative antimalarial medicines if a patient develops psychiatric or neurologic side effects.
The June and July FDA safety alerts included more than 77 pharmaceutical products that were getting labeling changes—28 were medications for psychiatric disorders.
Drugs intended for ADHD treatment represented over 50 percent of psychiatric drugs that received safety-labeling modifications—mainly for warning of increased risk of Raynaud’s phenomenon, a disorder causing poor circulation to extremities.
Medicines that contained valproate sodium, valproic acid, or divalproex sodium—commonly used to treat bipolar disorder—were the only psychiatric drugs to receive a black-box warning, which was for fetal development risk in pregnant women.
Detailed information on antipsychotic drugs that received safety modifications to their labeling is posted at http://www.fda.gov/safety/medwatch.
As Pfizer Pharmaceuticals Inc. continues to settle more than 2,700 lawsuits in the United States and the United Kingdom, it will be aiming to settle at least 200 more for its Canadian antismoking drug Champix (U.S. marketed as Chantix).
This summer, Ontario Superior Court ruled that the class-action lawsuit against the drugmaker, originally filed in 2012, will proceed after a judge’s dismissal of Pfizer’s appeal of the certification order.
The plaintiffs allege that Pfizer failed to warn Canadian Champix users about the associated psychiatric side effects such as depression, anxiety, and suicidal thoughts. The class action is open to any Canadians who took the drug between April 2007 and May 2010—when Champix was first sold in Canada and when the drug’s label was changed to include the most serious warnings.
Pfizer denied these allegations and claimed that it had provided appropriate and accurate information to regulators, physicians, and patients about the safety of Champix.
Researchers at the Centre for Gerontology and Rehabilitation at University College Cork in Ireland conducted a study evaluating the rate of cognitive decline in dementia patients receiving angiotensin-converting enzyme (ACE) inhibitors, medications commonly used to treat hypertension.
Published July 25 in BMJ Open, a study evaluated the effects of centrally acting ACE inhibitors (CACE-Is), which cross the blood-brain barrier, in 361 patients who were diagnosed with AD, vascular dementia, or a mix of both. Each participant—taking CACE-Is or not (NoCACE)—was evaluated over six months. In addition, 30 patients were newly prescribed CACE-Is to determine the drug’s impact on brain power. Cognitive decline was assessed using the Standardized Mini-Mental State Examination or the Quick Mild Cognitive Impartment.
Results showed that patients taking CACE-Is had a 14.3 percent lower rate of cognitive decline than their NoCACE counterparts. Data also showed a significant increase in brain power in those who were newly prescribed CACE-Is when compared with those already taking the CACE-Is and those not taking the drug.
The authors stated that “this [study] supports the growing body of evidence for the use of ACE inhibitors and other [blood-pressure lowering] agents in the management of dementia.” They further explained that longitudinal studies must be done to see more compounding effects and strong clinical benefits.
Alkermes recently announced the launch of its phase 2 study of the novel oral schizophrenia drug, ALKS 3831. ALKS 3831 is atypical antipsychotic that is a combination of an opioid modulator, ALKS 33, and the FDA-approved atypical antipsychotic, olanzapine.
With approximately 400 patients with schizophrenia enrolled, the double-blinded study will compare the dose-ranging effects of ALKS 3831 with olanzapine alone. In addition, phase 2 will investigate the impact of ALKS 3831 on metabolic factors and ALKS 3831’s ability to counteract olanzapine-induced weight gain that was observed in phase 1.
“This large, well-designed phase 2 study will provide data necessary for us to determine ALKS 3831’s ability to attenuate weight gain commonly associated with olanzapine treatment,” stated Elliot Ehrich, M.D., chief medical officer of Alkermes. Olanzapine is associated with the highest incidences and greatest amount of weight gain. ■