Med Check
Yale Recycles Failed Drug as Potential Alzheimer’s Therapy
The phrase “one man’s trash is another man’s treasure” may be applied to AstraZeneca’s drug AZD0530 after its development was halted by the company for the pharmacotherapy’s inability to rid solid tumors. However, new research from Yale suggests that the drug may be better suited as a therapy for Alzheimer’s disease (AD).
Using a mouse model of AD disease, Yale researchers found that AZD05030 was successful in blocking activation of the enzyme FYN that interrupts the synaptic connections between brain cells needed to retain memories, a key step in the development of AD.
“With this treatment, cells under bombardment by beta amyloid plaques show restored synaptic connections and reduced inflammation, and the animal’s memory, which was lost during the course of the disease, comes back,” said the study’s senior author Stephen Strittmatter, M.D., the Vincent Coates Professor of Neurology and Neurobiology. According to Strittmatter, a phase 2 clinical trial that will run for 12 months is under way.
FDA Issues Final Guidance on Labeling for Abuse-Deterrent Opioids
The Food and Drug Administration (FDA) has issued a final guidance to assist industry in the development of opioid drug products with abuse-deterrent properties. The agency is suggesting, for example, that opioid medicines be manufactured in a way that will make it difficult for the drugs to be snorted or injected, methods used by some patients to get a more intense high.
“The science of abuse-deterrent medication is rapidly evolving, and the FDA is eager to engage with manufacturers to help make these medications available to patients who need them,” said FDA Commissioner Margaret Hamburg, M.D., in a news release.
The FDA is working with many drugmakers to support research and development in abuse-deterrent opioids, as well as helping the companies quickly navigate through drug regulatory path of the FDA. Though the final guidance does not pertain to generic opioid products, the FDA stated that a draft guidance addressing such medicines is under way.
The final guidance can be accessed here.
Less Weight Gain Associated With Schizophrenia Drug
Alkermes has pushed its schizophrenia drug ALKS-3831 back into the spotlight after the company released more positive results from clinical trials testing the drug’s ability to stabilize weight gain associated with antipsychotics.
In January, Alkermes showed that ALKS-3831 was capable of inducing antipsychotic efficacy equivalent to olanzapine with less weight gain than that of olanzapine over three months. Now the drug developers are showing that patients whose body weight increased, on average, by 4.3 percent after taking olanzapine for three months had only a 0.1 percent increase in weight after switching to ALKS-3831 in the second three-month stage of the clinical trial. Meanwhile, those who received ALKS-3831 over the entire six-month clinical trial showed only a 0.5 percent increase in weight.
With phase 2 trials completed, Alkermes discussed in a press release its plans for meeting with the FDA to design a phase 3 study. The company hopes to begin pivotal development by the end of year.
FDA Reports Results of Investigation on Zyprexa-Related Deaths
After examining the cause of elevated levels of Zyprexa Relpevv (olanzapine pamoate)—a long-acting injectable antipsychotic intended to treat schizophrenia—in two patients who died, the FDA has determined the results of the study to be inconclusive.
According to the FDA, the agency was “unable to exclude the possibility that the deaths were caused by rapid, but delayed, entry of the drug into the bloodstream following intramuscular injection.” Much of the drug-level increase could have occurred after death, stated the FDA, “a finding that could explain the extremely high blood levels found in the two patients who died three to four days after receiving injections of appropriate doses of Zyprexa Relprevv.”
On the basis of the information reviewed, the FDA is not recommending any changes to the current prescribing or use of Zyprexa Relprevv injection. The FDA noted that health care professionals should continue to follow the Zyprexa Relprevv Patient Care Program Risk Evaluation and Mitigation Strategy (REMS) requirements and label recommendations. Here are some of the notable requirements of the REMS:
For a patient to receive treatment, the prescriber, health care facility, patient, and pharmacy must all be enrolled in the Zyprexa Relprevv Patient Care Program.
Zyprexa Relprevv injections must be administered at a REMS-certified health care facility with ready access to emergency response services.
Patients must be continuously monitored at the REMS-certified health care facility for at least three hours after an intramuscular injection.
Patients receiving Zyprexa Relprevv must be accompanied to their destination from the health care facility.
Health care professionals and patients are encouraged to report adverse events and side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
Schizophrenia Drug Shows Positive Phase-2 Results
New York City–based company Intra-Cellular Therapies reported positive results from a phase 2 trial of its schizophrenia drug ITI-007—a novel pharmacological agent that is a serotonin 5-HT2A receptor antagonist, an inhibitor of the serotonin reuptake transporter, and a modulator of dopamine receptor phosphoprotein and glutamate.
Results from the randomized, controlled trial of 335 participants with schizophrenia showed that treatment with ITI-007 led to statistically significant improvements in positive and negative symptoms experienced by patients who were administered 60 mg of the newly developed drug for four weeks, whereas placebo did not. In addition, the finding showed that—compared with placebo—those individuals who took 60 mg to 120 mg of the drug had significantly lower levels of metabolic measures including glucose, insulin, triglycerides, and LDL cholesterol.
The drug was well tolerated, with no difference in side effects observed between the 60 mg and placebo groups. The most frequent adverse event reported was sedation, occurring only in those receiving the 120 mg dose.
The drug is in phase 3 clinical development for schizophrenia. ■
