A number of groundbreaking new drugs, related to low testosterone, postpartum depression and multiple sclerosis, have been approved for use by the US FDA.

The US Food and Drug Administration (FDA) set an all-time record for new drug approvals in 2018 with 59 novel drugs and biologics approved by the agency's Center for Drug Evaluation and Research (CDER).

TESTOSTERONE PILL

The US Food and Drug Administration (FDA) has approved oral testosterone undecanoate to treat low testosterone in men whose condition is caused by pituitary tumours or certain genetic disorders, such as Klinefelter syndrome. The pill, marketed as Jatenzo, isn’t intended for age-related hypogonadism.

In a phase 3 study among men with low testosterone, 87% of those receiving oral testosterone undecanoate achieved average testosterone levels in the normal range (the primary endpoint). Common side effects included high blood pressure, headache, decreased HDL cholesterol, increased prostate-specific antigen, increased hematocrit and nausea.

The drug will carry a boxed warning about the risk for blood pressure increases. Individual patient risk for cardiovascular disease must be assessed prior to considering treatment.

NOVEL DRUG FOR POSTPARTUM DEPRESSION

The FDA has approved brexanolone (marketed as Zulresso) to treat postpartum depression in women. This novel drug works by restoring levels of the metabolite allopregnanolone, which can be implicated in the development of postpartum depression.

Brexanolone is administered as a continuous intravenous infusion over 60 hours. Patients must be enrolled in the drug’s Risk Evaluation and Mitigation Strategy (REMS) program to be treated. Brexanolone may cause severe drowsiness and sudden loss of consciousness, so patients must have continuous pulse oximetry monitoring during the infusion.

They also must be monitored when interacting with their children during the infusion, and they should not drive, operate machinery, or perform other potentially dangerous activities until drowsiness has resolved post-treatment.

Brexanolone’s approval was based on findings from two placebo-controlled trials — one in patients with moderate postpartum depression and the other in patients with severe depression. In both trials, the drug outperformed placebo in terms of depressive symptoms after the infusion and at 30 days.

Dr Peter Roy-Byrne, editor-in-chief of NEJM Journal Watch Psychiatry, commented: “The major advantage of this drug is the rapid onset of action. A disadvantage is that patients will need to be treated in a special hospital-like facility capable of careful monitoring, and this may pose logistical problems. Only time will tell what its place will be in the armamentarium of treatments for this very serious and at times underappreciated condition.”

NEW ORAL DRUG TO TREAT MS

The 22nd WHO Expert Committee on the Selection and Use of Essential Medicines will be debating an application for three medicines for multiple sclerosis, submitted by the Multiple Sclerosis International Federation – glatiramer acetate, fingolimod and ocrelizumab.

The FDA has approved Mayzent (siponimod) tablets, by Novartis, to treat adults with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing remitting disease, and active secondary progressive disease. The efficacy of siponimod was shown in a clinical trial of 1 651 patients that compared it to placebo in patients with SPMS who had evidence of disability progression in the prior two years and no relapses in the three months prior to enrollment.

The primary endpoint of the study was the time to three-month confirmed progression in disability. The fraction of patients with confirmed progression of disability was statistically significantly lower in the siponimod group than in the placebo group. It also decreased the number of relapses experienced by these patients. In the subgroup of patients with non-active SPMS, the results were not statistically significant.

The most common adverse reactions reported by patients receiving the drug in the clinical trials include headache, high blood pressure and liver function test increases.