FDA Grants Orphan Drug Designation to P-BCMA-101 CAR Therapy for R/R Multiple Myeloma


The FDA has granted P-BCMA-101 with an orphan drug designation for the treatment of patients with relapsed and/or refractory multiple myeloma.

Eric Ostertag, MD, PhD

Eric Ostertag, MD, PhD

Eric Ostertag, MD, PhD

The FDA has granted P-BCMA-101 with an orphan drug designation for the treatment of patients with relapsed and/or refractory multiple myeloma.1

The autologous chimeric antigen receptor (CAR) T-cell therapy is composed of self-renewing, long-lived stem cell memory T cells that are targeted to B-cell maturation antigen (BCMA), which is expressed on multiple myeloma cells. P-BCMA-101 requires only plasmid DNA and mRNA, in contrast to other CAR T- cell therapies that require a viral vector. This method is less costly and results in a higher percentage of the favorable stem cell memory T phenotype.2

The FDA designation was given to P-BCMA-101 as a result of the promising safety and efficacy data seen in the phase I trial (NCT03288493).

“FDA orphan designation is an important regulatory milestone in the continued development and commercialization of P-BCMA-101,” Eric Ostertag, MD, PhD, chief executive officer of Poseida, the company developing the CAR T-cell product, said in a statement. “P-BCMA-101 has demonstrated outstanding potency, with strikingly low rates of toxicity in our phase I clinical trial. In fact, the FDA has approved fully outpatient dosing in our phase II trial starting in the second quarter of 2019.”

The orphan drug designation from the FDA is granted to drugs and biologics that are intended to treat rare diseases that affect less than 200,000 people in the United States and allows for increased assistance from the FDA in the accelerated development of the agent.

The dose-escalation trial2enrolled heavily pretreated patients with relapsed/refractory multiple myeloma who had received at least 3 prior treatment regimens, including a proteasome inhibitor and an immunomodulatory drug; the majority of patients had received 6 prior regimens or more and had prior exposure to daratumumab (Darzalex; 91%) and/or had undergone an autologous stem cell transplant (83%). Patients were not required to have any level of BCMA at baseline.

All patients went through apheresis to harvest T cells before P-BCMA-101 could be manufactured and administered intravenously. A conditioning regimen consisting of 3 days of cyclophosphamide at 300 mg/m2/day and fludarabine at 30 mg/m2/day was given prior to administration of P-BCMA-101.

According to results presented at the 2018 ASH Annual Meeting, 23 patients received treatment with P-BCMA-101 in 1 of 5 dose cohorts and no dose-limiting toxicities were observed at any dose.2

All 3 patients who received P-BCMA at a mean dose of 857 x 106achieved a response, with 2 achieving a very good partial response. The third patient achieved a partial response and minimal residual disease negativity. Seven patients received a mean dose of 456 x 106and the objective response rate was 43% in these patients. In the 7 patients who received a mean dose of 152 x 106, the objective response rate was 71%. A minor response or better was seen in 13 of 19 evaluable patients by IMWG criteria.

Grade 1/2 cytokine release syndrome was suspected in 2 patients but was minimal and transient. Neurotoxicity was observed in 1 case of grade 2 CAR T-cell—related encephalopathy syndrome with grade 3 confusion. Neutropenia, neutrophil, and platelet count decreases were seen more frequently at any grade, as well as anemia and infections.

The phase II trial of P-BCMA-101 is expected to begin in the second quarter of 2019 with potential biologics license application filing by the end of 2020, according to Poseida.


  1. Poseida Therapeutics Receives US FDA Orphan Drug Designation for P-BCMA-101 for the Treatment of Multiple Myeloma [press release]. San Diego, CA: Poseida Therapeutics Inc; May 13, 2019. https://bit.ly/2YjCMHM. Accessed May 13, 2019.
  2. Gregory T, Cohen AD, Costello CL, et al. Efficacy and safety of P-Bcma-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM).Blood.2018;132(suppl 1):1012. doi: 10.1182/blood-2018-99-111419.
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