BioMarin provides update on PEG-PAL Phase 2 clinical study for phenylketonuria

BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) announced today an update in the Phase 2 clinical study of PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase) for the treatment of phenylketonuria (PKU). Data reported in this announcement reflect preliminary results as of July 23, 2010.  Complete top-line results are expected in the fourth quarter of 2010.

Key highlights of the study:

• 23 adult patients have been enrolled in the study, and patients have been followed for a median of 111 days.  The first enrolled patients have been in the study for over 300 days.
• Seven patients have received at least 1 mg/kg/week for at least four weeks in several different dosing frequencies (up to three times per week).  Of these, six have had Phe levels below 600 umol/L for at least three weeks and in some cases, up to three months.  Their baseline Phe levels were reduced from a median of 1,293 umol/L to a median of 527 umol/L, representing an approximate 60% reduction in blood Phe. Two patients have had blood Phe levels documented below 5 umol/L, and their physicians have substantially liberalized their diet.
• An additional 16 patients have been treated with lower doses at shorter periods of time and are continuing to have their doses escalated according to the protocol.  Importantly, several patients escalating to higher doses are also beginning to have their Phe levels trend down.
• Three patients have chosen not to continue in the ongoing program for personal reasons, though one patient also had generalized skin reaction at the time of discontinuation.
• Injection site reaction is the most common treatment emergent adverse event, occurring in 43% of patients.  Injection site reactions are generally mild to moderate, self-limited and unaccompanied by other sequelae.  Other less common adverse events are also mild to moderate, self limited and do not interfere with continuation in the study.
• Three other patients have had generalized skin reaction during the study, all self-limited and managed with medical therapy and transient dose reduction.  All patients have experienced Phe levels lower than pre-treatment baseline levels after the rashes resolved.
• Antibody and PK analyses are underway.
• Dose and schedule optimization, as well as enrollment of additional cohorts of patients, are ongoing.  Additionally, liberalization of diet will be further studied.

"Based on my positive experiences to date, I am optimistic that PEG-PAL can improve phenylalanine levels in patients with PKU with an acceptable safety profile," stated Dr. Nicola Longo, Professor of Pediatrics and Adjunct Professor of Pathology at the University of Utah and Clinical Investigator in the PEG-PAL Phase 2 trial. "There remains an unmet need in PKU for patients who are unable to control their phenylalanine levels with diet or Kuvan and hopefully, PEG-PAL can offer another treatment option to these patients."

"We are very encouraged by these preliminary findings, especially given the safety concerns as we entered the Phase 2 trial," said Hank Fuchs, M.D., Chief Medical Officer of BioMarin. "Assuming the continuation of positive safety and efficacy trends in this ongoing study, we believe these data could support advancement to a Phase 3 trial at the end of 2011 with blood Phe level reductions as a primary endpoint for product registration. Getting to this stage has involved a tremendous amount of work by both the BioMarin team and our various collaborators. As with any program, we developed and tested many candidates before settling on PEG-PAL. Among the collaborators that helped us in this process we would like to particularly thank the Stevens laboratory at The Scripps Research Institute, Scriver laboratory at McGill University, and the local and national PKU communities."

The Phase 2 clinical trial is an open-label, multi-center study to be conducted in a series of dose-escalating cohorts from 0.001 mg/kg.  The primary treatment period of eight once weekly injections at a fixed dose will be followed by dose and frequency optimization and an extension period where doses can be increased up to 2.0 mg/kg/week.

The primary objective is to evaluate the effect of PEG-PAL on blood Phe concentrations in subjects with PKU.  The secondary objectives are to evaluate the safety and tolerability, immune response and steady state pharmacokinetics of subcutaneous injections of multiple dose levels of PEG-PAL.