Sponsor decision

Study 701-301 is a single-arm, open-label, switchover study in patients with late-onset Pompe disease who have been receiving treatment with recombinant human acid alpha-glucosidase (rhGAA) for 48 weeks or longer. Ambulatory patients who have mild to moderate respiratory impairment will switch directly to receive BMN 701 20 mg/kg by IV infusion every other week. All participants will receive active drug. No dose of existing therapy will be missed - experimental drug is started immediately.

Inclusion Criteria:

• Willing and able to provide written informed consent, after the nature of the study has been explained, and prior to any study-related procedures.

• Diagnosed with late-onset Pompe disease based on 2 currently or previously documented GAA gene mutations, and endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed by dried blood spot or whole blood assay.

• Has received prior treatment with commercial rhGAA as defined by ALL of the following:

  1. has received treatment with commercial rhGAA for ≥ 48 weeks (but no more than 20% of the study population can have received treatment for ≥ 6 years).
  2. has received > 80% of all scheduled treatments in the prior 48 weeks and ≥ 4 out of the prior 6 scheduled treatments.
  3. has received and completed the last two infusions without a drug-related adverse event resulting in dose interruption.
  4. has received last treatment of commercial rhGAA ≥ 10 and ≤ 31 days prior to anticipated initiation of treatment with BMN 701.

• ≥ 18 years of age at the time of enrollment in the study.

• Sexually active subjects must be willing to use two known effective methods of contraception while participating in the study and for at least 4 months following the last dose of BMN 701.

• Females of childbearing potential must have a negative pregnancy test at Screening and Baseline visits and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.

• Has ≥ 30% predicted upright FVC and < 80% predicted upright FVC.

• Has ≤60% predicted MIP.

• Is able to ambulate ≥75 meters and ≤500 meters on the 6MWT conducted during the Screening visit (use of assistive devices such as walker, cane, or crutches, is permitted with consistent use throughout the study).

• Is willing and able to comply with all study procedures.

Exclusion Criteria:

• Use of any investigational product or investigational medical device within 4 weeks prior to Screening, or requirement for any investigational agent other than BMN 701 prior to completion of at least the first 24 weeks of all scheduled study assessments.
• Received any investigational medication for Pompe disease within the prior 12 months.
• Has a diagnosis of diabetes and/or is currently being treated with or anticipated to require treatment with hypoglycemic agents during the course of the study.
• Has been treated with any immunosuppressive medication other than glucocorticosteroids within the prior 12 months.
• Requires noninvasive ventilatory support while awake and in the upright position.
• Has previously been enrolled to this study.
• Breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
• Concurrent disease, medical condition, or extenuating circumstance that, in the opinion of the Investigator, might compromise subject safety, study treatment compliance and completion of the study, or the integrity of the data collected for the study.
• Has known hypersensitivity to BMN 701 or its excipients.