FDA Grants P-BCMA-101 CAR T-Cell Therapy Orphan Drug Designation for Myeloma

The FDA has granted an orphan drug designation to the autologous CAR T-cell therapy P-BCMA-101 for the treatment of patients with relapsed/refractory multiple myeloma.

Eric Ostertag, MD, PhD

Eric Ostertag, MD, PhD

Eric Ostertag, MD, PhD

The FDA has granted an orphan drug designation to the autologous CAR T-cell therapy P-BCMA-101 for the treatment of patients with relapsed/refractory multiple myeloma.1

The designation is based on results of a phase I trial (NCT03288493), which demonstrated tolerability and responses with P-BCMA-101 in this patient population.2

“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 developer of the CAR T-cell product, said in a press release. “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.”

P-BCMA-101 is comprised of self-renewing, long-lived stem cell memory T cells that are targeted to BCMA, which is known to be expressed on multiple myeloma cells. P-BCMA-101 requires only plasmid DNA and mRNA, which differs from other CAR T-cell therapies that require a viral vector. This method is said to not only lead to a higher percentage of the favorable stem cell memory T phenotype, but is also less expensive.

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

In the phase I dose-escalation trial, heavily pretreated patients with relapsed/refractory multiple myeloma who had received ≥3 prior treatment regimens, including a proteasome inhibitor and an immunomodulatory drug, were enrolled. The majority of patients received ≥6 prior regimens 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 underwent 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 daily and fludarabine at 30 mg/m2 daily was administered prior to administration of P-BCMA-101.

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

All 3 patients who received P-BCMA at a mean dose of 857 x 106 achieved 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 106 and the objective response rate (ORR) was 43% in these patients. In the 7 patients who received a mean dose of 152 x 106, the ORR 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 reported 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 a 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. Published 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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