september 2024

High-Cost Therapy Profile

Detailed information about Intravenous (IV) Obecabtagene autoleucel

September 27, 2024

Oncology/ cellular therapy 

Obecabtagene autoleucel Intravenous (IV)

Autolus

 

Proposed indications 

Relapsed/refractory (R/R) adult B-cell acute lymphoblastic leukemia (ALL) 
 

FDA approval timeline 

Nov. 16, 2024 

  • Orphan drug

  • Regenerative Medicine Advanced Therapy (RMAT)
 

Place in therapy 

Obecabtagene autoleucel (obe-cel) is an autologous chimeric antigen receptor (CAR) T cell therapy that uses a fast off-rate CD19 binder, reducing toxicity and T cell exhaustion, and improving persistence and high levels of durable remissions compared to existing CD19-directed CAR T cell therapies in adults with R/R B-cell ALL.  

  • If approved, obe-cel will compete with the other CD19 CAR T cell therapies; tisagenlecleucel (Kymriah) is approved in up to 25-year-olds in refractory or in second or later relapse and brexucabtagene autoleucel (Tecartus) is approved in the adult R/R B-cell ALL setting 

  • While all three CAR T cell therapies demonstrate high response rates, obe-cel’s improved safety profile may differentiate it from the other agents 

  • In non-comparative clinical trials in patients with R/R B-cell ALL, the rates of grade ≥ 3 cytokine release syndrome (CRS) were 2.4% with obe-cel, 26% with Tecartus, and 48% with Kymriah; likewise, serious neurologic toxicities were reported at rates of 7.1% with obe-cel, 35% with Tecartus, and 22% with Kymriah 

  • Obe-cel achieved durable responses with 40% reaching ongoing remission without subsequent hematopoietic stem cell transplant (HCT) and 18% receiving HCT while in remission after obe-cel infusion 

  • Results of median event-free survival, 12-month event-free survival rate, and overall survival rate were the same regardless of HCT suggesting that obe-cel would potentially be considered as a standalone treatment 

  • Obe-cel is also in phase 1 clinical trial to evaluate use in pediatric patients with R/R B-cell ALL and aggressive mature B-cell non-Hodgkin lymphoma (B-NHL), and in adults with severe, refractory systemic lupus erythematosus (SLE) 
     

Understanding your data 

Obe-cel is a CAR T cell therapy that was created with a fast target binding off-rate that minimizes excessive activation of the programmed T cells. Clinical trials demonstrated that its fast off-rate profile reduced toxicity and T cell exhaustion and resulted in improved persistence and high levels of durable remissions compared to existing CD19-directed CAR T cell therapies in adults with R/R B-cell ALL. Clinical trials evaluating obe-cel in R/R B-cell ALL are limited and include the following: 

  • NCT04404660: An open-label, multi-centre, phase 1b/2 study evaluating the safety and efficacy of obe-cel, a CAR T cell treatment targeting CD19, in adult patients with R/R B-cell ALL 

  • NCT06173518: A single-arm, open-label, multi-centre, phase 1b study evaluating the safety and preliminary efficacy of obe-cel in pediatric patients with CD19-positive R/R B-cell ALL and aggressive mature B-NHL 

Identification of patients would reflect the clinical trials criteria listed in the studies above, as well as diagnosis codes identified from claims data requiring among others: 
 

Common Measurable Inclusion Criteria: 

  • Adult aged ≥ 18 years 

  • R/R B-cell ALL 
     

Common Measurable Exclusion Criteria: 

  • History of any of the following conditions: 

  • Burkitt’s leukemia/lymphoma 

  • Active or latent hepatitis B virus (HBV) 

  • Active hepatitis C virus (HCV) 

  • Human immunodeficiency virus (HIV) 

  • Human T-lymphotropic virus type 1 (HTLV-1) or type 2 (HTLV-2) 

  • Prior CD19 targeted therapy, other than Blincyto 

Apendix 

Category 

Procedure codes 

R/R B-cell ALL 

ICD-10: C91.00, C91.02 

Burkitt’s leukemia/lymphoma 

ICD-10: C83.7, C91.A 

Active or latent HBV 

ICD-10: B16.0, B16.1, B16.2, B16.9, B17.0, B18.0, B18.1, B19.1 

Active HCV  

ICD-10: B17.1 

HIV 

ICD-10: B20, B97.35 

HTLV-1 or HTLV-2 

ICD-10: B97.33, B97.34, C91.5 

Prior CD19 targeted therapy, other than Blincyto 

HCPCS:  

J9349 tafasitamab-cxix (Monjuvi) 

J1823 inebilizumab-cdon (Uplizna)  

J9359 loncastuximab tesirine-lpyl (Zynlonta) 

Clinical deep dive 

Disease state overview 

Acute lymphoblastic leukemia (ALL) is a type of cancer of the blood and bone marrow that creates immature blood cells, instead of mature ones. In ALL, the bone marrow produces an excessive number of lymphocytes. Nearly 30% of patients with ALL are diagnosed at ≥ 45 years of age and nearly 14% are diagnosed at ≥ 65 years of age. In addition, about 75% of adult cases develop from B-cell lineage, and 25% emerge from T cell precursors. Risk factors for developing ALL in adulthood include age > 70 years, prior treatment with chemotherapy or radiation therapy, environmental radiation exposure, and certain genetic conditions (e.g., Down syndrome). In general, prognosis of ALL decreases with age, with a 5-year survival rate of 20% to 40% in adults. 
 

Epidemiology 

The American Cancer Society estimates about 6,550 new cases of ALL and about 1,330 deaths are expected in 2024. Compared to other cancers, ALL is relatively rare; in 2021, there were an estimated 115,294 people living with ALL in the US. The risk of developing ALL is highest in children under 5 years of age and rising again after 50 years of age. 
 

Treatment 

Pharmacologic agents that target B-cell surface antigens have demonstrated improved response in R/R B-cell ALL. This includes select tyrosine kinase inhibitors (in Ph+ B-cell ALL only; complete remission [CR]/CR with incomplete hematologic recovery [Cri] rates, 42% to 47%), a bispecific CD19-directed CD3 T-cell engager (Blincyto; CR rate, 43%), an anti-CD22 monoclonal antibody (inotuzumab ozogamicin [Besponsa]; CR/CRi rate, 78.4%), and CD19-directed CAR T cell therapies (Tecartus and Kymriah; CR rate, 69% to 81%). Allogeneic HCT may also be considered in eligible patients. Choice of treatment should be individualized based on the presence or absence of target antigen (CD19 and CD22), prior exposure to one of these agents, patient immune status, and disease burden. HCT is currently the only treatment considered a cure for R/R ALL, but many patients are not eligible for HCT. Notably, the CAR T cell therapies have served as a bridge, allowing patients with initial poor remission status to become eligible for HCT; however, high rates of toxicities, including CRS and neurologic toxicities, have complicated their use. 
 

Drug and clinical trial overview 

The ongoing, open-label, single-arm, phase 1b/2 FELIX trial evaluated obe-cel in adults with R/R B-cell ALL. The study included 126 patients with morphological disease ≥ 5% bone marrow (BM) blasts (cohort A), or in second or later CR/CRi with measurable residual disease (MRD) (cohort B), or with isolated extramedullary disease (EMD) (cohort C). In the trial, Ph+ B-cell ALL was reported in 27% of patients. Patients enrolled had a median of 2 prior lines of therapy (range, 1 to 6). Patients underwent leukapheresis and received bridging therapy as needed (inotuzumab-containing therapy or Blincyto) while obe-cel was manufactured (median time from vein-to-release, 22 days). After lymphodepletion with chemotherapy (cyclophosphamide and fludarabine), obe-cel was administered IV at a target dose of 410 × 106 cells as a leukemic burden-adjusted split dose on day 1 and day 10 (± 2 days).  

Topline results of pooled data from all three cohorts revealed, at a median follow-up of 11 months (range, 0.9 to 30.6 months), CR/CRi (primary endpoint) occurred in 77% of patients who received obe-cel, with CR occurring in 57% of patients. Among evaluable responders, 96% were considered to have MRD-negative status. The median duration of response (DOR) was not reached. Grade ≥ 3 CRS occurred in 2.4% of patients, and grade ≥ 3 immune effector cell associated neurotoxicity syndrome (ICANS) occurred in 7.1% of patients. 

Name 

Manufacturer 

Route of administration 

Mechanism of action 

Proposed/studied indication 

Status 

SMART 101 

Smart Immune SAS 

IV 

Allogeneic cellular product 

ALL 

Phase 2 

WU-CART-007 

Wugen 

IV 

CAR T 

ALL 

Phase 2 
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