A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).

New approvals
Zokinvy okayed as first therapy for rare premature aging diseases
Eiger BioPharmaceuticals’ Zokinvy (lonafarnib capsules) has been approved for reducing the risk of death from Hutchinson-Gilford progeria syndrome and treating certain processing-deficient progeroid laminopathies in patients aged 1 year or older.

The rare genetic diseases cause premature aging and death. Accumulation of defective progerin or progerin-like protein in cells accelerates cardiovascular disease in these patients, and most die from heart failure, heart attack, or stroke before they reach the age of 15 years. Treatment options until now have been limited to supportive care and therapies that mitigate disease-related complications.

Zokinvy acts by blocking the build-up of defective progerin or progerin-like protein. Its effectiveness in treating Hutchinson-Gilford progeria syndrome was demonstrated in two single-arm trials in 62 patients, who were compared with matched, untreated patients. The lifespan of patients receiving Zokinvy increased by an average of 3 months in the first 3 years of therapy and of 2.5 years over 11 years follow-up.  

The application was granted priority review designation. The therapy received orphan drug and breakthrough therapy designations, and the manufacturer received a rare pediatric disease priority review voucher.

Oxlumo gets go-ahead as first drug for rare genetic kidney-related disorder
Alnylam’s Oxlumo (lumasiran) has been approved as the first treatment for primary hyperoxaluria type 1 (PH1), a rare genetic disorder that causes recurrent kidney stones and progressive loss of kidney function.

“The approval of Oxlumo represents a great triumph of community involvement to address a rare disease. It is a result of input from patients, treating physicians, experts and sponsors at a patient-focused drug development meeting and through other collaborative efforts,” said Norman Stockbridge, MD, PhD, director of the Division of Cardiology and Nephrology in the FDA’s Center for Drug Evaluation and Research.

Patients with PH1 produce an excess of oxalate that combines with calcium, causing kidney stones and calcium deposits in the kidneys. In addition to kidney damage and possible failure, the build-up can also damage organs such as the heart, bones, and eyes. Oxlumo’s mechanism of action involves targeting and decreasing the production of oxalate.

The therapy was evaluated in two studies in patients with PH1 whose ages ranged from 4 months to 61 years. In the randomized, placebo-controlled ILLUMINATE-A study in patients aged 6 years or older, 26 patients received a monthly injection of Oxlumo, followed by a maintenance dose every 3 months, and 13 patients received placebo injections. Those receiving the study drug showed an average 65% reduction of oxalate in the urine, compared with an average 12% reduction in controls. After 6 months, 52% of patients treated with Oxlumo attained a normal 24-hour urinary oxalate level. None of the placebo patients attained normal level.

All 16 patients in the open-label ILLUMINATE-B study were younger than 6 years and all received Oxlumo. Investigators used a different measure for urinary oxalate levels than that used in the first study. By the sixth month, there was an average 71% decrease in urinary oxalate among the patients.

Oxlumo received orphan drug designation, and the application was granted breakthrough therapy designation. The manufacturer received a rare pediatric disease priority review voucher.

New indications
Xofluza picks up expanded indication for postexposure prevention
Genentech’s Xofluza (baloxavir marboxil) has received an expanded  indication for postexposure prevention of influenza (flu) for patients aged 12 years or older after contact with a person with flu.

The drug also has a new formulation – it is now available in granular form for mixing with water in additional to its original tablet form in its 2018 approval as a treatment for uncomplicated flu in patients aged 12 years or older.

Xofluza’s safety and efficacy for postexposure prevention was supported by findings from a double-blind, controlled trial of 607 patients aged 12 years or older and randomized to receive Xofluza or placebo after exposure to a person with flu.

One percent of patients receiving Xofluza were infected with the flu virus and presented with fever and at least one respiratory symptom in the first 10 days after exposure, compared with 13% of those who received placebo.

Debra Birnkrant, MD, director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research, noted in a press release that the expanded indication is an important option for patients and providers in the upcoming flu season, which will be unprecedented because of the ongoing COVID-19 pandemic.