Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy

This study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to
determine the efficacy and safety of ataluren 10, 10, 20 mg/kg in patients with
nonsense-mutation (nm) dystrophinopathy. Patients will be randomized in a 1:1 ratio to
ataluren 10-, 10-, 20-mg/kg dose level or placebo. Patients will receive study drug TID at
morning, midday, and evening. It is planned that 220 patients will be enrolled and patients
will undergo 48 weeks of blinded treatment prior to the final analysis. Study assessments
will be performed at clinic visits every 8 weeks. It is anticipated that an open-label
extension study will be available to patients (who successfully complete the double-blind
study) in countries where ataluren is not commercially available.

Inclusion Criteria:

- Ability to provide written informed consent (parental/guardian consent if
applicable)/assent per local requirements.

- Male sex.

- Age ≥7 and ≤16 years.

- Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical
symptoms or signs (eg. proximal muscle weakness, waddling gait, and Gowers' maneuver)
by 6 years of age, an elevated serum creatinine kinase level, and ongoing difficulty
with walking.

- Documentation of the presence of a nonsense point mutation in the dystrophin gene as
determined by gene sequencing from a laboratory certified by the College of American
Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an
equivalent organization.

- Documentation that a blood sample has been drawn for confirmation of the presence of a
nonsense mutation in the dystrophin gene.

- Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a
minimum of 6 months immediately prior to start of study treatment, with no significant
change in dosage or dosing regimen (not related to body weight change) for a minimum
of 3 months immediately prior to start of study treatment and a reasonable expectation
that dosage and dosing regimen will not change significantly for the duration of the
study.

- Ability to walk ≥150 meters unassisted during the screening 6-minute walk test.
Patients need to be below the protocol-specified threshold for %-predicted 6MWD.

- Results of the 2 Baseline 6MWD results must be determined as valid and results of the
Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD.

- Baseline 6MWD (mean of valid Day 1 and Day 2 values) must be no more than a 20%
reduction from the valid Screening 6MWD.

- Confirmed screening laboratory values within the central laboratory ranges (hepatic,
renal, and serum electrolyte parameters)

- Willingness to abstain from sexual intercourse or employ an approved method of
contraception during the period of study drug administration and 6-week follow-up
period.

- Willingness and ability to comply with scheduled visits, drug administration plan,
study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

- Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of
study treatment.

- Initiation of systemic corticosteroids therapy within 6 months prior to start of study
treatment.

- Change in systemic corticosteroid therapy (eg, change in type of drug, dose
modification not related to body weight change, schedule modification, interruption,
or reinitiation) within 3 months prior to start of study treatment.

- Any change (initiation, change in type of drug, dose modification, schedule
modification,interruption, discontinuation, or reinitiation) in prophylaxis/treatment
for congestive heart failure (CHF) within 3 months prior to start of study treatment.

- Ongoing use of coumarin-based anticoagulants (eg. warfarin), phenytoin, tolbutamide,
or paclitaxel.

- Prior therapy with ataluren.

- Known hypersensitivity to any of the ingredients or excipients of the study drug

- Exposure to another investigational drug within 3 months prior to start of study
treatment.

- History of major surgical procedure within 6 weeks prior to start of study treatment.

- Ongoing immunosuppressive therapy (other than corticosteroids).

- Ongoing participation in any clinical trial (except for studies specifically approved
by PTC Therapeutics).

- Expectation of major surgical procedure (eg, scoliosis surgery) during the 12-month
treatment period of the study.

- Requirement for daytime ventilator assistance. Note: Evening ventilator assistance and
use of bi-level positive airway pressure (Bi-PAP) therapy is allowed.

- Uncontrolled clinical symptoms and signs of CHF (American College of
Cardiology/American Heart Association Stage C or Stage D).

- Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition,
behavioral disorder, alcoholism, drug abuse), medical history, physical findings (eg.
lower limb injury that may affect 6MWT performance), ECG findings, or laboratory
abnormality that, in the investigator's opinion, could adversely affect the safety of
the subject, makes it unlikely that the course of treatment or follow-up would be
completed, or could impair the assessment of study results.