Clinical trials

Orphazyme is developing arimoclomol in four indications. Orphazyme has fully recruited a Phase II/III trial in NPC (trial results expected Q3 2018), initiated a Phase II/III trial in sIBM in August 2017 and plans to start a Phase II/III trial in ALS in Q3 2018.

In addition, a Phase II Proof-of-Concept trial in Gaucher disease will be initiated in Q2 2018. If positive, all three Phase II/III trials are intended to form basis for a single study filing in each respective indication.

The Company expects to have completed all three phase II/III trials by the end of 2020, with the first potential marketing authorization in 2020.

Arimoclomol Program

    Protein-aggregation diseases

  • sIBM
    A Phase II/III trial was initiated in August 2017 in the USA and Europe to establish efficacy and is intended to form the basis for registration. Orphazyme conducts the trial in collaboration with the University of Kansas and the University College London.

    The trial is a randomized, double-blinded, placebo-controlled Phase II/III trial assessing efficacy and safety of arimoclomol 400 mg three times a day in patients with sIBM. The primary endpoint analysis is after 12 months, while the trial duration will continue for up to 20 months. 150 patients (75 per arm) will be enrolled, randomized 1:1 to receive arimoclomol or placebo. The primary efficacy endpoint will be the change from baseline to 12 months in the IBMFRS total score. Secondary endpoints include the change from baseline to month 20 in the IBMFRS sum score (durability of treatment) and changes from baseline to month 12 and 20 in different measures of strength and function.

    The average changes in these outcomes will be compared between placebo and arimoclomol at 12 and 20 months, respectively. Results from the Phase II/III trial are expected in H1 2020.
  • ALS
    Based on the mechanism of action of arimoclomol that is expected to be relevant across the broad ALS patient population, the results in the Phase II SOD1 ALS trial trend effect observed in the open label portion of the Phase II trial in sporadic ALS and encouraging feedback from FDA, Orphazyme is working on a Phase II/III trial design intended to support a marketing authorization in the broad ALS population. The Company is currently evaluating a design that will include clinical and genetic enrichment strategies to ensure homogeneous disease progression in the trial.

    The next step is to finalize the protocol for submission to EMA for scientific advice prior to enrolling patients in the trial. Expectedly, the trial will be a randomized, double-blinded, placebo-controlled Phase II/III trial assessing efficacy and safety of arimoclomol 400 mg three times a day. The trial is expected to enrol approximately 200-300 patients and is planned to start in Q3 2018 and results are expected in H2 2020.
  • Lysosomal storage diseases

  • NPC
    Patients are randomized 2:1 to arimoclomol and placebo, respectively, and assessed for a total of 12 months of randomized treatment, followed by open-label treatment of up to 24 months. The purpose of the trial is to assess the efficacy and safety of arimoclomol when administered in addition to patient’s current prescribed best standard of care. The trial was fully enrolled in Q2 2017 and trial completion is expected in H2 2018. The primary endpoint is disease severity as measured by the NPC clinical severity score.

    Contingent on positive results of the trial, Orphazyme expects to file an NDA (US) and MAA (EU) in H2 2019 with potential approval in H1 2020.
  • Gaucher disease
    Patients are to be randomized 1:1:1:1 into four treatment arms – active treatment at three different doses and placebo, and assessed for six months. Following the placebo-controlled period, the placebo group will be re-randomized into one of the three active treatment groups for a six-month extension.

    The primary endpoint in this trial is chitotriosidase levels in CSF and blood. Chitotriosidase is a known marker of Gaucher disease, because it is found in high levels in patients whose immune cells have accumulated an excess lipid burden.

    The Phase II clinical trial, is anticipated to start in Q2 2018.

New Molecular Entities Program

  • NME
    Orphazyme is developing a new series of HSP-amplifying drugs based on its expertise and know-how about the convergences of HSPs, protein aggregation, and cellular recycling systems and how these can be targeted for therapeutic benefit. As of the date hereof, Orphazyme has several leads that constitute potentially new intellectual property opportunities. These molecules are currently being vetted and will be prioritized based on their suitability for specific diseases.