– Highly statistically significant and clinically meaningful results –

– 63% mean blood Phe reduction in primary analysis population (p<0.0001) –

SOUTH PLAINFIELD, NJ, USA I May 17, 2023 I PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced that the primary endpoint was achieved in the APHENITY, Phase 3 registration-directed clinical trial of sepiapterin in adult and pediatric patients with phenylketonuria (PKU).

“The positive results from the APHENITY trial bring us one step closer to providing a therapy that could deliver meaningful benefit to PKU patients,” said Matthew B. Klein, M.D., Chief Executive Officer, PTC Therapeutics. “The Phe reductions observed in the placebo-controlled portion of the study are consistent with, and, in some cases, exceed the magnitude of Phe reductions recorded in the open label portion of the study. We look forward to meeting with regulatory authorities to discuss the path to approval.”

The placebo-controlled portion of the study included 98 patients in the primary analysis population. The mean percent Phe reduction in sepiapterin treated patients was 63%. In the subset of classical PKU patients, the mean percent Phe reduction was 69%. Minimal reductions in Phe levels were observed in the placebo treated patients resulting in a highly statistically significant sepiapterin treatment benefit (p<0.0001). Sepiapterin was generally well tolerated with no serious adverse events.

Today’s Conference Call and Webcast  
PTC will hold a conference call at 8 AM EDT today to discuss this news. To access the call by phone, please click here to register and you will be provided with dial-in details. To avoid delays, we recommend participants dial in to the conference call 15 minutes prior to the start of the call. The webcast conference call can be accessed on the Investor section of the PTC website at https://ir.ptcbio.com/events-presentations. A replay of the call will be available approximately two hours after completion of the call and will be archived on the company’s website for 30 days following the call.

APHENITY was a global double-blind, placebo-controlled, registration-directed study which enrolled 156 children and adults with PKU. Participants were randomized to receive sepiapterin or placebo for six weeks with the primary endpoint being reduction in blood phenylalanine levels. The trial consisted of two parts. Part 1 was a run-in phase, during which all screened subjects received sepiapterin for two weeks. Only those subjects who demonstrated a reduction in phenylalanine levels of 15% or more from baseline in Part 1 were randomized to receive either sepiapterin or placebo in Part 2 of the clinical trial. The primary analysis population consists of those who had greater than 30% reduction in phenylalanine levels from baseline during Part 1 of the trial. The primary outcome measure is the reduction of blood phenylalanine levels from baseline compared to Weeks 5 and 6 in patients from Part 2 of the clinical trial. All patients are eligible to enroll in an open label long term clinical trial designed to further evaluate the long-term safety and durable effect of sepiapterin.

About Sepiapterin
Sepiapterin (formerly PTC923) is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, which is a critical enzymatic cofactor involved in the metabolism and synthesis of numerous metabolic products. Sepiapterin is a more bioavailable precursor than exogenously administered synthetic BH4 and has the potential to treat the broad range of PKU patients.

About Phenylketonuria
Phenylketonuria (PKU) is a rare, inherited metabolic disease, which affects the brain.1 It is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine.1 If left untreated or poorly managed, phenylalanine – an essential amino acid found in all proteins and most foods – can build up to harmful levels in the body. This causes severe and irreversible disabilities, such as permanent intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems.1 Newborns with phenylketonuria initially don’t have any symptoms, but symptoms are usually progressive, and damage caused by toxic levels of phenylalanine in the first few years of life is irreversible.2,3 Diagnosis of phenylketonuria usually takes place during newborn screening programs.4 There are an estimated 58,000 people with phenylketonuria globally.

About PTC Therapeutics, Inc.
PTC is a science-driven, global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC’s ability to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC’s mission is to provide access to best-in-class treatments for patients who have little to no treatment options. PTC’s strategy is to leverage its strong scientific and clinical expertise and global commercial infrastructure to bring therapies to patients. PTC believes this allows it to maximize value for all its stakeholders. 


  1. de Groot MJ, Hoeksma M, Blau N, et al. Mol Genet Metab 2010;99:S86–S89.
  2. Phenylketonuria (PKU). Available at: https://www.mayoclinic.org/diseases-conditions/phenylketonuria/symptoms-causes/syc-20376302. Accessed October 2021.
  3. Blau N, van Spronsen FJ, Levy HL. Lancet 2010;376:1417–1427.
  4. Al Hafid N, Christodoulou J. Transl Pediatr 2015;4(4):304–317.

SOURCE: PTC Therapeutics