FDA lifts partial hold on tazemetostat trials

Photo by Esther Dyson

The U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The FDA had placed the hold in April, and this halted U.S.-based enrollment of new patients in tazemetostat clinical trials.

Now, Epizyme, Inc., the company developing tazemetostat, is in the process of reopening enrollment in all company-sponsored trials in the U.S.

The FDA had placed the partial hold on tazemetostat trials after an adverse event was observed in a pediatric patient on a phase 1 study.

The patient, who had advanced poorly differentiated chordoma, developed secondary T-cell lymphoblastic lymphoma (T-LBL) while taking tazemetostat. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.

“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” said Robert Bazemore, president and chief executive officer of Epizyme.

Due to this adverse event and the partial clinical hold, Epizyme began to assess the risk of T-LBL and other secondary malignancies potentially associated with tazemetostat.

The company also assessed the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials.

Epizyme concluded that the benefits of tazemetostat outweigh the risks, and the risk of T-LBL appears confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.

Epizyme convened a panel of external scientific and medical experts who reviewed and validated the company’s findings.

“The team at Epizyme has worked diligently in collaboration with external experts and FDA over the past several months, culminating in decisions . . . to lift the partial clinical hold and allow re-opening of enrollment in our clinical trials,” Bazemore said.

He noted that the company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials.

However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies.

Bazemore said the lifting of the partial clinical hold allows Epizyme to turn its full attention to key priorities, including plans to submit a new drug application for tazemetostat in epithelioid sarcoma.

The company also plans to begin preparing for a potential new drug application for tazemetostat in follicular lymphoma.

Tazemetostat is currently under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid tumor malignancies. The drug is also being studied as part of combination therapy for non-small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).

In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.

Now that Epizyme has resolved the U.S. hold on tazemetostat trials, the company is working to resolve partial clinical holds placed in France and Germany to resume trial enrollment in those countries.

Photo by Esther Dyson

The U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The FDA had placed the hold in April, and this halted U.S.-based enrollment of new patients in tazemetostat clinical trials.

Now, Epizyme, Inc., the company developing tazemetostat, is in the process of reopening enrollment in all company-sponsored trials in the U.S.

The FDA had placed the partial hold on tazemetostat trials after an adverse event was observed in a pediatric patient on a phase 1 study.

The patient, who had advanced poorly differentiated chordoma, developed secondary T-cell lymphoblastic lymphoma (T-LBL) while taking tazemetostat. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.

“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” said Robert Bazemore, president and chief executive officer of Epizyme.

Due to this adverse event and the partial clinical hold, Epizyme began to assess the risk of T-LBL and other secondary malignancies potentially associated with tazemetostat.

The company also assessed the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials.

Epizyme concluded that the benefits of tazemetostat outweigh the risks, and the risk of T-LBL appears confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.

Epizyme convened a panel of external scientific and medical experts who reviewed and validated the company’s findings.

“The team at Epizyme has worked diligently in collaboration with external experts and FDA over the past several months, culminating in decisions . . . to lift the partial clinical hold and allow re-opening of enrollment in our clinical trials,” Bazemore said.

He noted that the company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials.

However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies.

Bazemore said the lifting of the partial clinical hold allows Epizyme to turn its full attention to key priorities, including plans to submit a new drug application for tazemetostat in epithelioid sarcoma.

The company also plans to begin preparing for a potential new drug application for tazemetostat in follicular lymphoma.

Tazemetostat is currently under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid tumor malignancies. The drug is also being studied as part of combination therapy for non-small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).

In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.

Now that Epizyme has resolved the U.S. hold on tazemetostat trials, the company is working to resolve partial clinical holds placed in France and Germany to resume trial enrollment in those countries.

Photo by Esther Dyson

The U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on trials of tazemetostat, an EZH2 inhibitor being developed to treat solid tumors and lymphomas.

The FDA had placed the hold in April, and this halted U.S.-based enrollment of new patients in tazemetostat clinical trials.

Now, Epizyme, Inc., the company developing tazemetostat, is in the process of reopening enrollment in all company-sponsored trials in the U.S.

The FDA had placed the partial hold on tazemetostat trials after an adverse event was observed in a pediatric patient on a phase 1 study.

The patient, who had advanced poorly differentiated chordoma, developed secondary T-cell lymphoblastic lymphoma (T-LBL) while taking tazemetostat. The patient has since discontinued tazemetostat and responded to treatment for T-LBL.

“This remains the only case of T-LBL we’ve seen in more than 750 patients treated with tazemetostat,” said Robert Bazemore, president and chief executive officer of Epizyme.

Due to this adverse event and the partial clinical hold, Epizyme began to assess the risk of T-LBL and other secondary malignancies potentially associated with tazemetostat.

The company also assessed the overall risks and benefits of tazemetostat treatment, conducting a review of the published literature and an examination of efficacy and safety data across all of its tazemetostat trials.

Epizyme concluded that the benefits of tazemetostat outweigh the risks, and the risk of T-LBL appears confined to pediatric patients who received higher doses of the drug. The phase 1 pediatric study in which the patient developed T-LBL included higher doses of tazemetostat than those used in the phase 2 adult studies.

Epizyme convened a panel of external scientific and medical experts who reviewed and validated the company’s findings.

“The team at Epizyme has worked diligently in collaboration with external experts and FDA over the past several months, culminating in decisions . . . to lift the partial clinical hold and allow re-opening of enrollment in our clinical trials,” Bazemore said.

He noted that the company is not making any substantial changes to trial designs or the patient populations involved in tazemetostat trials.

However, Epizyme is modifying dosing in the pediatric studies, improving patient monitoring, and making changes to exclusion criteria to reduce the potential risk of T-LBL and other secondary malignancies.

Bazemore said the lifting of the partial clinical hold allows Epizyme to turn its full attention to key priorities, including plans to submit a new drug application for tazemetostat in epithelioid sarcoma.

The company also plans to begin preparing for a potential new drug application for tazemetostat in follicular lymphoma.

Tazemetostat is currently under investigation as monotherapy in phase 2 trials of follicular lymphoma and solid tumor malignancies. The drug is also being studied as part of combination therapy for non-small cell lung cancer and diffuse large B-cell lymphoma (DLBCL).

In August, Epizyme announced its decision to stop developing tazemetostat for use as monotherapy or in combination with prednisolone for patients with DLBCL. However, tazemetostat is still under investigation as a potential treatment for DLBCL as part of other combination regimens.

Now that Epizyme has resolved the U.S. hold on tazemetostat trials, the company is working to resolve partial clinical holds placed in France and Germany to resume trial enrollment in those countries.