MedCheck: Zunveyl for Alzheimer’s, Erzofri for Schizophrenia, Gene Therapy and Parkinson's, and more

In July the U.S. Food and Drug Administration (FDA) approved Zunveyl (benzagalantamine), formerly known as ALPHA-1062, for the treatment of mild to moderate Alzheimer’s disease, Alpha Cognition announced. Alpha Cognition stated that benzagalantamine is designed to eliminate drug absorption in the gastrointestinal tract, which may help avoid the gastrointestinal side effects associated with galantamine that often lead patients with Alzheimer’s to discontinue their medication.

The approval was based on data from three studies that demonstrated benzagalantamine was bioequivalent to galantamine, which was approved for mild to moderate Alzheimer’s disease in 2001. A bioequivalence study is designed to compare the pharmacological properties of two similar drugs. In this instance, the company showed benzagalantamine achieved concentrations of medication in the body similar to both the immediate-release and extended-release formulations of galantamine.

The FDA has approved Erzofri (paliperidone palmitate) extended-release injectable suspension for treating schizophrenia and schizoaffective disorder in adults, Luye Pharma announced in July. The drug is approved as a monotherapy and as an adjunct to mood stabilizers and antidepressants. It is administered once a month.

Erzofri was developed in China but was approved as a new drug under the 505(b)(2) pathway in the U.S. based on studies comparing multiple doses of the drug with Invega brand paliperidone palmitate products by Janssen. The FDA’s 505(b)(2) process allows the FDA to consider pre-existing data when reviewing a new drug application, even if the applicant did not develop the data.

Erzofri was approved with a black box warning stating that elderly patients with dementia-related psychosis who are treated with antipsychotic medications have an increased risk of death and warning that this drug is not approved for use in that population.

In July the FDA granted Fast Track designation to AB-1005, an investigational gene therapy in development by Bayer AG and Asklepios BioPharmaceutical, Inc. (AskBio) for the treatment of Parkinson’s disease, AskBio announced. The FDA Fast Track is a process designed to expedite the development and review of drugs that treat serious conditions and fill an unmet medical need.

FDA granted Fast Track designation to AB-1005 based on a phase 1b trial that evaluated the safety and clinical effect of the therapy. AB-1005 was delivered via neurosurgical infusion to the putamen in the brains of 11 patients with mild or moderate Parkinson’s disease. Patients then kept Parkinson’s disease motor diaries to record their symptoms, and clinicians used the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) to assess symptom severity.

At 18 months, patients with mild Parkinson’s disease had an average 1.3-hour reduction in “on” time and a 1.1-hour increase in “off” time per day during waking hours. ("On" time is when Parkinson's medications are effective and patients’ motor symptoms are controlled. "Off" time is when Parkinson's symptoms return between medication doses.) However, patients with moderate Parkinson’s disease reported a 2.2-hour improvement in good “on” time and a 1.7-hour reduction in “off” time per waking day.

The FDA issued a complete response letter to Orexo regarding its New Drug Application (NDA) for OX124, a high-dose naloxone rescue medication in development for reversing opioid overdose. The letter indicates the need for an additional human factors study—a study to assess how usable and safe the device would be for its intended users in a real-life environment. The letter did not request additional clinical or non-clinical studies.

The FDA accepted Orexo’s NDA for OX124 in November. The NDA included data from a study of healthy volunteers where OX124 showed a significantly faster and higher absorption of naloxone compared with intramuscular dosing with an injection reference product.

In July FDA granted Fast Track designation to two potential therapies for Alzheimer’s disease: Lomecel-B by Longeveron and JNJ-2056 (formerly known as ACI-35.030) by AC Immune.

Lomecel-B is a living cell product made from medicinal signaling cells derived from the bone marrow of young, healthy adult donors. These cells release growth factors and other proteins, such as anti-inflammatory cytokines that reduce inflammation. These cells also stimulate nearby stem cells and other cells to promote regenerative and repair responses in the body.

The FDA granted Fast Track designation for Lomecel-B for the treatment of mild Alzheimer’s disease based on data from the phase 2 CLEAR MIND study. In the study, 49 patients aged 60 to 85 years who had mild Alzheimer’s disease were randomized to receive either one of three dosing regimens of Lomecel-B or placebo on the first day of their participation, then once a week at week 4, week 8, and week 12. At week 39 there was one serious adverse event reported in each treatment group and no serious adverse events in the placebo group. Patients in the low-dose treatment group and the pooled treatment group had improvements in the Composite Alzheimer Disease Score compared with patients in the placebo group.

JNJ-2056 is an immunotherapy that targets phosphorylated tau, a protein thought to play a role in Alzheimer’s disease. JNJ-2056 received Fast Track designation for the treatment of early Alzheimer’s disease based on the results of a phase 1b/2a trial. In the study, patients aged 50 to 75 years with early Alzheimer’s disease who were immunized with JNJ-2056 developed antibodies against extracellular phosphorylated tau. Their antibody response was sustained and could be periodically boosted over 72 weeks.

Another trial, the phase 2b ReTain trial, is recruiting participants with preclinical Alzheimer’s disease to see if JNJ-2056 can help delay or prevent the onset of cognitive impairment in this population. Patients will be randomized to receive intramuscular injections of JNJ-2056 or placebo for a maximum of four years. ■