FDA Updates: Blood Cancers, Orphan Drug Designations Get Priority


In a busy week, FDA approved ground-breaking therapies in hematologic cancers and issued Orphan Drug designations in areas of significant unmet need.

Third CAR T-Cell Therapy Approved. Nearly three years after the first one made history,Tecartus (brexucabtagene autoleucel) on Monday became the third chimeric antigen receptor (CAR) T-cell therapy to win FDA approval, this time for patients whose mantle cell lymphoma (MCL) has relapsed or not responded to treatment. Tecartus is also the second CAR T-cell treatment for Kite Pharma, which gained approval for Yescarta in October 2017.

MCL is a form of non-Hodgkin lymphoma occurring in cells from the “mantle” zone of the lymph node. It is an aggressive cancer that mostly affects men over age 60. Approval was based on a trial of 60 adults who were followed for at least 6 months after their first objective disease response. The complete remission rate after treatment was 62%, and the objective response rate (ORR) was 87%.

As with other CAR T-cell treatments, Tecartus will be manufactured by collecting a patient’s T cells and genetically altering them to target and kill lymphoma cells. These personalized, engineered T cells are then infused into the patient. It is also subject to a Risk Evaluation and Mitigation Strategy due to the possibility of cytokine release syndrome and neurologic toxicities.

Monjuvi Combo Approved in DLBCL. Late Friday, Monjuvi (tafasitamab-cxix) received approval to be used in combination with lenalidomide in adult patients with diffuse large B-cell lymphoma (DLBCL) as the next treatment after initial chemotherapy. This approval will change the treatment landscape for patients with DLBCL who are not eligible for an autologous stem cell transplant. MorphoSys and Incyte are developing Monjuvi, a humanized Fc-modified cytolytic CD19 monoclonal antibody, for several B-cell malignancies. The treatment uses propriety technology from Xencor to improve the binding affinity of receptors to the CD19 and boost the effectiveness of the process that targets and kills cancer cells.

Approval is based in 2019 trial trials that showed a 55% ORR, including a 37% complete response rate. The median duration of response was 21.7 months. Common adverse events included neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.

DLBCL is the most common subtype of non-Hodgkin lymphomas, causing 18,000 US cases per year. Most common among seniors, DLBCL is also more common among those with HIV, an autoimmune disease, or if they have had an organ transplant. Some patients have CAR T-cell treatment for DLBCL, but this treatment is costly with more serious side effects.

Second BLA for bluebird bio. Bristol Myers Squibb and bluebird bio announced Wednesday they have submitted a second Biologics License Application to FDA for idecabtagene vicleucel (ide-cel), their investigational B-cell maturation antigen–directed (BCMA) chimeric antigen receptor (CAR) T-cell therapy for adults with relapsed and refractory multiple myeloma.

Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells, causing the CAR T-cells to multiply kill set loose the cell-killing effect of the BCMA-expressing cells. Application is based on results from the phase 2 KarMMa study, presented in May during the American Society of Clinical Oncology 2020 Virtual Scientific program. Investigators reported an ORR Of 73%, including 33% with a complete response or stringent complete response. Median duration of response was 10.7 months, and 19 months for those with the complete or stringent complete responses. Cytopenia and cytokine release syndrome were the most commonly reported adverse events.

Orphan Drug Status for Inovio’s RRP Candidate. On Wednesday, FDA granted orphan drug designation to INO-3107, a DNA medicine to treat recurrent respiratory papillomatosis (RRP). This rare disease is caused by human papillomavirus (HPV) types 6 and 11 infections and creates noncancerous tumor growths, leading to life-threatening airway obstructions that can progress to cancer. The typical treatment is surgery to repeated surgeries to remove the tumor growth, which was often repeated multiple times a year.

The open label INO-3107 phase 1/2 trial is recruiting 63 patients with HPV 6 and/or 11 who have had at least two surgical interventions in the past three years. Last year, Inovio published data from a pilot study of INO-3016 for HPV 6-caused RPP, which showed the immunotherapy allowed two patients who each needed two surgeries a year to delay surgery significantly; one was surgery-free for 584 days and the other was surgery-free for 915 days.

PKD Candidate Gets Orphan Drug Status. Regulus Therapeutic’ investigational therapy for RGLS4326, an investigational therapy to treat autosomal dominant polycystic kidney disease (ADPKD), received orphan drug designation Wednesday. ADPKD is the most common type of a group of genetic diseases that lead to end-stage renal disease, morbidity, and early death.

The genetic mutations that drive PKD cause fluid-filled cysts to form on the kidneys, causing these vital organs to grow from the size of a fist to up to 30 pounds. Patients with PKD experience extreme pain, hypertension, urinary tract infections, and can have strokes. The most common form, ADPKD, is inherited from one parent and accounts for 90% of the cases; a recessive form requires that both parents have the gene, and even then a child has 25% of developing PKD. About 500,000 people have this condition in the United States.

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