Chiesi USA, Inc.: PRX-102

We acknowledge receipt of your major amendment dated November 4, 2020, which extended the goal date by three months.

Satisfactory resolution of the remaining issues is required before this application may be approved.

We will communicate the outstanding issues to the facility no later than 10 business days after issuing this complete response letter.

You requested accelerated approval of PRX-102 based on a reduction in renal peritubular capillary globotriaosylceramide (Gb3) inclusions.

(agalsidase beta) on March 11, 2021, Fabrazyme is now available therapy?

Your product will no longer qualify for accelerated approval if it does not provide a therapeutic advantage over available therapy.

Prior to your resubmission, we recommend an End-of-Review meeting to discuss whether accelerated approval remains an appropriate pathway for your product.

An alternative approach to seeking accelerated approval may be to establish that the reduction in renal Gb3 inclusions with PRX-102 predicts clinical benefit, allowing for full approval of your product.

We recommend also discussing whether full approval may be a possible path forward for your product at the End-of-Review meeting.

Submit draft labeling that addresses our proposed revisions in the attached labeling.

An inspection of the Protalix Ltd. (FEl# 3008289067), Carmiel, Israel manufacturing facility is required before this application can be approved.

FDA must assess the ability of that facility to conduct the listed manufacturing operations in compliance with CGMP.

You may respond to deficiencies in this Complete Response Letter while the travel restrictions remain in effect.

However, even if these deficiencies are addressed, the application cannot be approved until the required FDA inspection is conducted and any findings are assessed with regard to your application.

It is unclear why you chose a window of only 2 hours after PRX-102 administration for defining an infusion-related reaction.

You also have not provided sufficient reasoning for excluding adverse events that you considered related to the infusion procedure rather than PRX-102. You have also not provided a clear narrative regarding premedication that was given in your safety database.

Food, Drug, and Cosmetic Act for mannitol inhalation powder, 40 mg.

The submitted data from the human factors (HF) validation studies do not provide sufficient evidence to demonstrate that healthcare providers can reliably and accurately perform the Mannitol Tolerance Test (MTT) to correctly identify the intended target patient population.

HF study results demonstrated several use errors and use difficulties with critical tasks in administering the MTT, which could result in healthcare providers prescribing the medication to patients who cannot tolerate mannitol inhalation powder.