FDA Approves BioMarin’s Palynziq for Phenylketonuria

The U.S. Food and Drug Administration (FDA) gave San Rafael, California-based BioMarin Pharmaceutical a thumbs-up for its Palynziq (pegvaliase-pqpz) to treat phenylketonuria (PKU).

Palynziq is a PEGylated recombinant phenylalanine ammonia lyase enzyme approved to cut blood phenylalanine (Phe) concentrations in PKU patients who have uncontrolled Phe concentrations higher than 600 micromol/L who are already on treatment. The drug is the first enzyme substitution therapy approved that targets the underlying cause of PKU.

PKU is a rare genetic disease. It is observed at birth and has a number of effects on the brain, which can cause seizures, and serious neurological and neuropsychiatric problems. Infants are screened at birth to guarantee early diagnosis.

“BioMarin is thrilled to be able to offer this important new therapy to adults with PKU who are unable to control their Phe levels with existing options,” said Jean-Jacques Bienaime, BioMarin’s chairman and chief executive officer, in a statement. “The approval of Palynziq is the culmination of more than a decade of perseverance by BioMarin employees dedicated to bringing treatments to PKU adult patients.”

The company expects to launch the drug commercially in the U.S. by the end of June. It is available only through the Palynziq REMS, a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).

The drug is being evaluated by the European Medicines Agency as well.

In its pivotal Phase III PRISM-2 clinical trial, the primary endpoint of change in blood Phe compared to placebo was met. Patients were randomized two-to-one to either continue their maintenance Palynziq dosage of 20 mg or 40 mg once daily or to receive matching placebo for eight weeks. The patients receiving Palynziq maintained their blood Phe concentrations compared to the withdrawal baseline. In the trial, 57 percent of patients were taking medical food at baseline and 16 percent were on a protein-restricted diet at baseline.

In a conference call with analysts, the company indicated the price for the drug will be $488 wholesale per unit. Patients generally require one to two units daily. On average, that suggests $267,180 per year up to $356,240 annually. Taking into discounts and rebates, as well as expected patient compliance, BioMarin believes the annual average net price for the drug will be $192,000.

Joseph Schwartz, analyst with Leerink, wrote in a note, “Given the black box warning (for anaphylaxis) and complications associated with the initial induction/titration phase, Palynziq sales are likely to be incremental contributors to BioMarin’s top line in the early years. And whereas BioMarin’s long-term goal of more than $1 billion Palynziq sales may be possible, this will require substantial uptake and compliance.”

The disorder is usually treated with a strict diet with low protein and Phe-free medical foods. BioMarin also markets Kuvan for the disorder, which is prescribed in combination with a low-Phe diet. Palynziq is designed to forego the specialized diet, and will likely be prescribed for patients who can’t otherwise control the disease.

BioMarin shares rose 2.74 percent Thursday after the approval was announced, with another rise of 4.8 percent after hours.

Christine Brown, executive director of the National PKU Alliance, has said in a statement that the drug is potentially a “game-changing therapy” for adults “who have struggled throughout their lives to control their Phe levels, despite rigorous management.”