While the maximum dose previously was 40 mg, this label expansion will enable patients to receive doses up to 60 mg. This maximum dose, the same used in Europe, is expected to help more U.S. patients benefit from Palynziq.
The 60 mg dose may be prescribed to patients who have been on 40 mg once daily continuously for at least 16 weeks, but have to control the levels of phenylalanine in the blood. If phenylalanine levels are still not controlled after 16 weeks on the 60 mg dose, prescribers are instructed to discontinue the treatment.
The approval was based on data from the PRISM Phase 3 studies, which showed that 19% of participants required a 60 mg dose to achieve an adequate response to Palynziq.
“Adding a maximum dose of 60 mg allows more patients to optimize and achieve treatment goals to keep blood Phe [phenylalanine] levels within the range set in the medical guidelines or within normal range,” Cary Harding, MD, said in a press release. Harding is a professor at the Oregon Health & Science University and the steering committee chair for the Palynziq program.
“BioMarin is pleased that the FDA has recognized the importance of including an additional dosing option to individuals with PKU. Consistent with the label in Europe, Palynziq is now available in the U.S. at doses of up to 60 mg,” said Jean-Jacques Bienaimé, chairman and CEO of BioMarin.
Palynziq is a modified form of the liver phenylalanine ammonia lyase, an enzyme responsible for breaking down the amino acid phenylalanine — one of the building blocks of proteins. The therapy is administered at home by subcutaneous (under-the-skin) injection.
Patients who fail to reach normal levels of phenylalanine in the blood – typically between 120 and 360 micromol (umol)/L — when using standard approaches, may be prescribed Palynziq. The therapy is approved for adults with PKU who have blood phenylalanine levels greater than 600 umol/L.
The PRISM program evaluating Palynziq in PKU patients included two Phase 3 clinical trials — PRISM-1 (NCT01819727) and PRISM-2 (NCT01889862) — and open-label extension trial (NCT03694353) that followed about 40 patients from prior trials who received Palynziq at doses greater than 40 mg a day.
Irrespective of the dose used, Palynziq lowered phenylalanine to target levels in two thirds (66%) of the 86 patients who received treatment for at least two years. Among those treated for three years, 66% also reached phenylalanine concentrations of 360 umol/L or lower.
Of the patients who achieved their first response at a dose of 60 mg once daily, a majority (67%) did so within 16 weeks of treatment.
Safety data from patients followed for more than six years in the open-label trial also showed that Palynziq’s safety profile was consistent with previous studies, irrespective of the dose. The rate and types of adverse events (side effects) were similar among patients receiving 20 mg, 40 mg, and 60 mg, showing that this higher dose also is safe in PKU patients.
“More than six years of long-term safety data further supports a well-characterized safety profile similar to the initial data and is important information to physicians considering a chronic therapy,” said Harding.
Currently, BioMarin’s Kuvan (sapropterin dihydrochloride) and Palynziq are the only approved treatments for PKU. The company also is developing a third treatment candidate for the condition, BMN 307, designed to be administered in a single dose.
“BioMarin remains committed to the PKU community and continues to build on our 15 plus years of research and development, which enabled us to deliver the first two PKU drug therapies,” said Bienaimé.
“We continue our commitment to further understand the safety and efficacy of our treatments for PKU. We are grateful to the study participants, investigators, study staff and BioMarin employees who were essential to enable this label expansion,” he added.
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