UNMC involved in FDA-approval of new therapy for genetic disease known as PKU

by Lisa Spellman
June 18, 2018

Image with file name: Jen_HarneyHorizontal.jpg

On May 25, the U.S. Food and Drug Administration approved Palynziq (pegvaliase-pqpz), a new enzyme substitution therapy for adults with a rare and serious genetic disease known as phenylketonuria (PKU).

That’s good news for Jennifer Harney, M.D., who was diagnosed at birth with PKU and participated in a clinical trial for three years headed by William Rizzo, M.D., professor of pediatrics at the University of Nebraska Medical Center’s Munroe Meyer Institute.

"The therapy has given me significantly improved energy and mental activity," Dr. Harney said.

"I’ve been able to include more dietary protein in what I eat and don’t need to restrict my meals so heavily (there’s several times in the past I would just skip meals if I was unable to eat what was provided) and don’t need to spend hours ordering, prepping, and storing specially created low-phenylalanine foods. That’s been a huge relief with my already busy schedule," she said.

All babies in the U.S. are screened at birth for PKU due to its severe consequences on the brain. Patients with PKU are born with the inability to break down phenylalanine (Phe), an amino acid present in protein-containing foods and high-intensity sweeteners used in a variety of foods and beverages.

Unmanaged, PKU can lead to neurological damage and intellectual impairment. Because the diagnosis requires strict adherence to a protein-free diet, Dr. Harney has had to avoid meat, fish, eggs, nuts and dairy her entire life.

The safety and effectiveness of the Palynziq enzyme substitution therapy was studied in two clinical trials in adult patients with PKU. The first trial was a randomized, open-label trial in patients treated with increasing doses of Palynziq administered as an injection up to a target dose of either 20 mg or 40 mg once daily.

The second trial was an eight-week, placebo-controlled, randomized withdrawal trial in patients who were previously treated with Palynziq. Patients treated with Palynziq achieved statistically significant reductions in blood phenylalanine concentrations from their pre-treatment baseline blood Phe concentrations.

PKU affects about 1 in 10,000 to 15,000 people in the United States. This new treatment will change lives, said Dr. Rizzo.

"What this enzyme therapy does is allow PKU patients, who have been on life-long protein restriction, to normalize their diet," he said.

Dr. Rizzo said he will now be able to prescribe the FDA-approved enzyme therapy for those patients who want it. He also continues to take part in an ongoing clinical trial for patients who need an even higher dose of the therapy than what was just approved by the FDA.

There are some side effects to the enzyme therapy.

Dr. Harney, who earned her medical degree from UNMC in 2011, said she experienced occasional hives and joint pain when she first started the enzyme therapy but has no side effects now and plans to continue to take the injections.

Other adverse reactions to the enzyme therapy include: hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, itchy skin, nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and diarrhea. 

The most serious adverse reaction in the Palynziq trials was anaphylaxis, which occurred most frequently within the first year of treatment as the dosage was increased.

Because of this serious risk, the labeling for Palynziq includes a boxed warning and the product is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REMS Program. Notable requirements of the Palynziq REMS Program include the following:

  • Prescribers must be certified by enrolling in the REMS program and completing training;
  • Prescribers must prescribe auto-injectable epinephrine with Palynziq;
  • Pharmacies must be certified with the program and must dispense only to patients who are authorized to receive Palynziq; 
  • Patients must enroll in the program and be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the risks and benefits of treatment with Palynziq; and
  • Patients must have auto-injectable epinephrine available at all times while taking Palynziq.

The FDA granted approval of Palynziq to BioMarin Pharmaceutical Inc.

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