FDA Approves Two Rare Cancer Therapies

Rare Daily Staff

The U.S. Food and Drug Administration approved two rare cancer therapies: TG Therapeutics’ Ukoniq for adult patients with relapsed or refractory marginal zone lymphoma and Bristol Myers Squibb’s CAR T therapy Breyanzi for Large B-cell lymphoma.

The FDA approved Ukoniq for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 based regimen and adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. The FDA gave these indications accelerated approval based on overall response rate. It said continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

MZL comprises a group of slow growing mature B-cell non-Hodgkin lymphomas (NHL). MZL is generally considered a chronic and incurable disease. With an annual incidence of approximately 8,200 newly diagnosed patients in the United States, MZL is the third most common B-cell NHL, accounting for approximately ten percent of all NHL cases.

FL is typically a slow growing form of NHL that arises from B-lymphocytes. It is the second most common form of NHL. FL is generally not curable and is considered a chronic disease, as patients can live for many years with this form of lymphoma. With an annual incidence in the United States of approximately 13,200 newly diagnosed patients, FL is the most common indolent lymphoma accounting for approximately 17 percent of all NHL cases.

Ukoniq is the first and only, oral, once daily, inhibitor of phosphoinositide 3 kinase (PI3K) delta and casein kinase 1 (CK1) epsilon. Accelerated approval was granted for these indications based on overall response rate (ORR) data from the phase 2 UNITY-NHL Trial. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial. This application was granted priority review for the MZL indication. In addition, Ukoniq was granted Breakthrough Therapy designation for the treatment of MZL and orphan drug designation for the treatment of MZL and FL.

“Despite treatment advances, MZL and FL remain incurable diseases with limited treatment options for patients who relapse after prior therapy and no defined standard of care,” said Nathan Fowler, professor of medicine at The University of Texas MD Anderson Cancer Center and the study chair of the UNITY-NHL MZL and FL cohorts. “With the approval of [Ukoniq] we now have a targeted, oral, once-daily option, offering a needed treatment alternative for patients.”  

 Separately, the FDA approved Bristol Myers Squibb’s Breyanzi, a CAR T cell therapy for adults with relapsed or refractory large B-cell lymphoma.

The FDA approved Breyanzi for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma not otherwise specified, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a rapidly growing, aggressive disease and the most common form of NHL, accounting for one out of every three cases diagnosed. Seventy-three percent of patients will not respond to or will relapse following second-line treatment or later. For patients who relapse or do not respond to initial therapies, conventional treatment options that provide sustained responses are limited and median life expectancy is about six months.

Breyanzi is a CD19-directed CAR T cell therapy designed to reduce variability of the CD8 and CD4 component dose. It is also formulated to enhance its expansion and persistence of itself.  Breyanzi has been granted Priority Medicines (PRIME) designation for R/R DLBCL in the European Union and a Marketing Authorization Application is currently under review by the European Medicines Agency.

The FDA approval of Breyanzi is based on data from the TRANSCEND NHL 001 trial in which 268 patients with relapsing or remitting LBCL received Breyanzi, the largest pivotal trial in third-line plus relapsing or remitting LBCL that included patients with a broad range of histologies and high-risk disease. In the trial, Breyanzi was administered in the inpatient and outpatient settings.

In the study, 192 patients were treated with Breyanzi at the dose of 50 to 110 x 106 CAR-positive viable T cells and evaluated for efficacy. Of these patients, 73 percent achieved a response, including 54 percent who had minimal or no detectable lymphoma remaining following treatment and 19 percent who achieved a partial response. Median duration of response was 16.7 months in all responders, and for patients who achieved a complete response, median duration of response was not reached. For patients with a best response of PR, median duration of response was 1.4 months. Of 104 patients treated with Breyanzi who achieved a best overall response of complete response, 65 percent had remission lasting at least six months and 62 percent had remission lasting at least nine months.

Serious adverse reactions occurred in 46 percent of patients. The most common nonlaboratory, serious adverse reactions (>2 percent) were cytokine release syndrome, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4 percent of patients. The most common nonlaboratory adverse reactions of any grade (≥20 percent) were fatigue, cytokine release syndrome, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

“People battling relapsed or refractory large B-cell lymphoma continue to face a challenging treatment journey, both physically and emotionally,” said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation. “Breyanzi is an innovative treatment that offers a new option for patients, and another reason for this community to maintain hope for the future.”