NOVATO, California — Not long ago, most people with long chain fatty acid oxidation disorder (LCFAOD) had few options for treatment other than snacking on low-fat, high-carbohydrate nutrients every 2 to 6 hours to prevent liver damage. But that has changed in the last 12 months.

Triheptanoin (Dojolvi®) on June 30, 2020, became the first and only treatment approved by the US Food and Drug Administration (FDA) for the treatment of LCFAOD. The treatment, approved by Health Canada on Feb. 17, 2021, is a highly purified, synthetic, 7-carbon fatty acid triglyceride specifically designed to provide medium-chain, odd-carbon fatty acids as an energy source and metabolite replacement.  

Camille Bedrosian, MD, chief medical officer and executive vice president of Ultragenyx, said her company has been offering the oral therapy to LCFAOD patients for several years through its compassionate use program.

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“It is gratifying to know that now the drug is available to a broad group of patients,” Bedrosian said in a recent interview with Rare Disease Advisor from her company’s headquarters in the San Francisco, California suburb of Novato.

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Camille Bedrosian, MD, chief medical officer and executive vice president of Ultragenyx (Credit: Ultragenyx)

Dr. Bedrosian is a trained hematologist and medical oncologist who began her career at Genetics Institute, a former biotechnology research and development company. She later worked at Alexion, whose drug sebelipase alfa (Kanuma®) is the only FDA-approved therapy for another liver disease, lysosomal acid lipase deficiency (LAL-D).

LCFAOD was first recognized as a distinct disease in the early 1970s, Dr. Bedrosian said.

“It’s always been present but it was not appreciated as a set of genetic disorders,” she explained. “Sometimes, patients with LCFAOD — newborns, infants, and very young children — would [officially] die from sudden infant death syndrome, and about 10% of those patients actually turned out to have long-chain fatty acid oxidation disorder.”

Ultragenyx CMO Dr. Camille Bedrosian Discusses the First FDA-Approved Treatment for LCFAOD

According to Jerry Vockley, MD, PhD, chief of medical genetics at Children’s Hospital of Pittsburgh in Pennsylvania, the disease affects 1 in 9300 people. Before newborn screening for LCFAOD became routine, mortality ranged from 60% to 90%, he said in a recent webinar. While mortality rates have dropped in recent years, comorbidities remain high.

Dr. Bedrosian estimated that between 2000 and 3500 Americans have the disease, with about 100 babies born with LCFAOD each year.

“There is still a very high premature mortality rate, and the quality of life for patients with LCFAOD is, you know, quite hampered by the disease and the condition,” she explained.

“Fasting is very dangerous for these individuals,” Dr. Bedrosian said. “Any infection, even moderate exercise, stress, lack of sleep, anything that stresses the body can put the individual at increased risk for these devastating consequences.”

She added: “I think about it as an energy tank. You can fill up the tank and the individuals have enough energy. But in settings where there is a great demand or there has been fasting, the energy source is rapidly depleted. And because these folks cannot use the long-chain fats, and they can’t make new glucose, so-called gluconeogenesis, they get into trouble.”

People with LCFAOD who go without eating quickly become hypoglycemic, because they cannot make ketones and are unable to metabolize fatty acids as a source of energy. 

“These individuals are at very high risk for unpredictable, precipitous, and life-threatening hypoglycemia, or cardiomyopathy, or the breakdown of muscle called rhabdomyolysis,” she said.

Triheptanoin is a liquid that’s added to food or beverages and taken 4 times a day. It provides up to 35% of a patient’s daily caloric intake.

A 500-ml bottle of the drug costs $4875 wholesale, or an average net price of $138,000 per patient per year, though Dojolvi will have an average net price of $46,000 in the first year of a patient’s life. A company spokesman told the San Francisco Business Times in 2020 that the “vast majority” of patients will have zero or “very low” out-of-pocket costs for the new therapy. 

“The drug is being reimbursed well, but if there is a challenge with reimbursement, we are there to help, and we would provide the drug free of charge, just as we did prior to approval with our compassionate access program,” she said. “For a condition like LCFAOD, that is critically important because often patients present in crisis in the ICU critically ill with either cardiomyopathy or hypoglycemia, and it’s imperative that they get the drug promptly.”