FDA Action Alert: Epizyme and Merck


January isn’t a particularly busy month for PDUFA dates for the U.S. Food and Drug Administration (FDA), with only two scheduled for the month. Here’s a look.


Epizyme’s Tazemetostat for Sarcoma

Cambridge, Massachusetts-based Epizyme has a target action date of January 23 for its tazemetostat. The New Drug Application (NDA) is for metastatic or locally advanced epithelioid sarcoma patients not eligible for curative surgery. The drug is under the FDA’s Priority Review.

The NDA is largely based on data from an ongoing Phase II trial of the drug in a 62-patient cohort with epithelioid sarcoma. Tazemetostat is an oral potent, first-in-class EZH2 inhibitor. It is being evaluated as a monotherapy in specific molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors, as well as in patients with follicular lymphoma, both with and without EZH2 activating mutations.

The drug is also being evaluated as a combination treatment for patients with diffuse large B-cell lymphoma.

In order to garner full approval, Epizyme indicated in July it would initiate a global confirmatory trial, which would compare tezemetostat in combination with doxorubicin compared to placebo plus doxorubicin in about 150 patients. The primary efficacy endpoint would be progression-free survival, with secondary endpoints of overall survival, disease control rate, overall response rate and duration of response.

On December 18, 2019, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11 to 0 in favor of recommending tazemetostat for this indication. Epithelioid sarcoma is a rare and aggressive soft tissue sarcoma marked by a loss of the INI1 protein. They are usually diagnosed in people between the ages of 20 and 40 years of age, and typically patients do not live past five years from diagnosis.

“We are incredibly pleased by ODAC’s unanimous support of the benefit-risk of tezemetostat in ES, and we appreciate the tremendous support received from sarcoma physicians and their medical teams, advocates, caregivers and most notably, patients with ES,” said Shefali Agarwal, Epizyme’s chief medical officer.”

Also, on December 18, 2019, the company submitted its NDA for tezemetostat for relapsed or refractory follicular lymphoma (FL), with or without EZH2 activating mutations, in patients who have received at least two prior lines of systemic therapy.


Merck’s Dificid for C. Diff Infections

Merck has a target action date of Jan. 24 for its Dificid (fidaxomicin) for oral suspension, and a supplemental NDA (sNDA) for a new indication for use of Dificid tablets and oral suspension for the treatment of Clostridium difficile (C. diff) infections in children aged six months are older. Both applications are under Priority Review.

Dificid is a macrolide antibacterial drug indicated in adults for treatment of C. diff-associated diarrhea (CDAD). C. diff is one of the most common causes of healthcare-related infections in U.S. hospitals, causing about 500,000 infections each year. It is associated with about 29,000 deaths within 30 days of individual diagnosis.

In October 2019, when the FDA accepted the submissions, Nicholas Kartsonis, senior vice president, Clinical Research, infectious diseases and vaccines, Merck Research Laboratories, said, “Evidence indicates the increasing incidence of C. difficile-associated diarrhea among hospitalized children. The filings for the pediatric indication for the new investigational oral suspension formulation of Dificid, as well as for Dificid tablets, underscore Merck’s focus and dedication to developing infectious disease treatments for those with unmet needs.”

The sNDA is built mostly on data from the Phase III SUNSHINE trial, which the company presented at IDWeek 2018 in San Francisco.



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