Investigational CFTR Amplifier PTI-428 Receives Orphan Drug Status in Europe

Investigational CFTR Amplifier PTI-428 Receives Orphan Drug Status in Europe

Proteostasis Therapeutics received orphan drug designation from the European Commission for its investigational CFTR amplifier PTI-428 in development for the treatment of cystic fibrosis (CF).

This recognition of the therapeutic potential of PTI-428 in Europe follows previously granted orphan drug, breakthrough therapy, and fast track designations from the U.S. Food and Drug Administration.

All of these designations are expected to support and expedite the clinical development, review, approval, and marketing of the CFTR modulator.

The European Commission’s final decision was based on a positive endorsement from the European Medicines Agency’s Committee for Orphan Medicinal Products.

“This designation by the [European Commission] is further validation of both PTI-428’s potential and PTI’s mission to offer additional disease modifying treatment options for CF,” Meenu Chhabra, president and CEO of Proteostasis Therapeutics, said in a press release.

PTI-428 is being developed to increase the amount of cystic fibrosis transmembrane conductance regulator (CFTR) — the protein that is defective in CF patients.

CFTR is required for transporting chloride ions through cell membranes, which helps generate a thin mucus the body needs to protect and lubricate organs and tissues. Abnormal or low levels of CFTR protein leads to an accumulation of thick mucus in organs, which can cause problems with breathing and digestion, the hallmark symptoms of CF.

Proteostasis Therapeutics is developing PTI-428 as part of its proprietary triple combination regimen that also includes PTI-808 (a CFTR potentiator), and PTI-801 (a third-generation CFTR corrector).

Recent results from a Phase 1 trial (NCT03500263) demonstrated that treatment with the triple combo for 14 days could effectively improve lung function, with a 5% increase in mean absolute ppFEV1 (percent predicted forced expiratory volume in one second), and reduce sweat chloride levels.

The company plans to further study these CFTR modulators in new Phase 2 trials. These studies will enroll CF patients with at least one F508del mutation (a common CF-causing mutation) who will receive either triple or double CFTR modulator combinations, or a placebo, for 28 days. These trials are expected to complete the enrollment phase by the end of 2019.

“We look forward to advancing PTI-428 in the clinic later this year, as part of the planned 28-day Phase 2 studies of our proprietary combination CFTR modulator treatments,” Chhabra said.

The company also anticipates starting Phase 3 trials for its CFTR modulators by mid-2020.


  1. John says:

    How can it be that Cf Life Saving Drugs are ‘on the shelf and ready’, yet unavailable in England, Wales and Northern Ireland three years on due to a continuing dispute over approval process and cost.
    Unused ‘out of date’ drugs thrown away unconscionably by Vertex AND a ‘compassionate use programme’ that demands that Cf patients must decline irreparably before the drug ‘may’ be provided ‘compassionately’ (when it’s too late). It’s abhorrent and tragic in equal measure.

    I am and remain angry & disgusted by those who process to care.

  2. julian leat says:

    Im 47 Cystic fibroses and at my age these drugs i need to extend my life and still same story no drugs in uk.

    In the age of the computer chip and bio science and we cant find a way around money for profits, if these triple drugs orkambi and symdeco are as good as they say why not free to all and give money back at a later stage . or pay as success on the drugs .. re im burse ment fees.

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