dm+d

Unassigned

New Medicines

Tab-celEpstein-Barr virus (EBV)-associated post transplant lymphoproliferative disorder (PTLD) - second-line after rituximab

Information

Tab-cel
New molecular entity
Pierre Fabre
Atara

Development and Regulatory status

None
Pre-registration (Filed)
Phase III Clinical Trials
Yes
Yes
Nov 21Filed to the EMA. An EU approval decision is expected H2 2022, based on CHMP accelerated assessment [4].
Nov 21EU filing is imminent. Based on the requests from FDA, Atara will provide additional analyses of CMC data already generated. The FDA has not requested additional studies or manufacturing lots. Atara plans to complete the BLA submission in Q2 22 [13].
Nov 21Atara has an exclusive agreement with Pierre Fabre for the commercialisation of tab-cel in Europe, the Middle East, Africa, and other select emerging markets. Atara will retain full rights to tab-cel in other major markets, including North America, Asia Pacific, and Latin America [13].
Sep 21EMA grant accelerated assessment, Atara plan to submit MAA Nov 21 [12].
May 21The Company is continuing to invest in US commercial readiness activities ahead of planned US launch in H1 2022. In addition, Atara is in discussions with potential partners for the commercialisation of tab-cel® in Europe [11].
May 21Atara is working toward completing a BLA submission in the US in Q3 2021. It has submitted a letter of intent to the EMA, starting the process for a submission of an EU MAA for tab-cel® in patients with EBV+ PTLD expected in Q4 2021 [11].
Jan 21Atara Biotherapeutics has not yet initiated the BLA submission as the company is awaiting a procedural decision from the FDA related to how the historical non-pivotal data should be presented [9].
Nov 20Atara has agreement with FDA on several key topics related to the regulatory package, including a rolling submission is acceptable for the BLA, it can complete the BLA submission with the ALLELE study currently enrolled patients with at least six months follow-up for duration of response, and the FDA will consider the following as supportive data to the pivotal study in the BLA clinical module: the PII trials conducted at Memorial Sloan Kettering (MSK); Atara’s PII multicentre expanded access protocol (201 EAP study); and, the SPU program [8].
Nov 20Atara remains on track to initiate a rolling BLA submission to the FDA for patients with EBV+ PTLD by end of 2020, and expects to finalise the BLA submission in Q3 2021. Following discussion with the PRIME team and after EMA approval of the Pediatric Investigation Plan (PIP) expected in December 2020, Atara is on track to file in the EU for patients with EBV+ PTLD in H2 2021 [8].
Feb 20Atara has submitted a Pediatric Investigation Plan to the EMA. Following an agreement with EMA on the PIP, it plans to submit a tab-cel® EU marketing authorization application for patients with EBV+ PTLD in 2021. Atara may seek partners to aid in its commercialisation efforts in select markets [7].
Jul 19Company plans to file in US 2H 2020 [6]
Feb 19Atara Biotherapeutics announced that, they are in discussion with EMA and US FDA regarding ongoing development of tabelecleucel and Atara´s intension to align on a global regulatory strategy for patients with EBV-Associated Post Transplant Lymphoproliferative Disorder [4].
Jan 17Atara plans to file in EU in 2018. The Conditional MAA will be based on data from PI and II trials, which were conducted at the Memorial Sloan Kettering Cancer Center (MSKCC) and will be supported by the PIII MATCH and ALLELE trials [2].
Oct 16Granted PRIME status by the EMA for treatment of patients with rituximab refractory EBV-PTLD following haematopoietic cell transplant (HCT) [2].
Mar 16Granted orphan drug status in EU [2].
Feb 16Granted orphan drug status in US [2].
Jun 15EMA classifies EBV-CTL as an Advanced Therapy Medicinal Product (ATMP) [2].
Mar 15Granted breakthrough therapy status in US [2].

Category

An ex vivo allogeneic somatic cell therapy, made from T-cells collected from the blood of healthy donors and ‘activated’ by exposure to Epstein-Barr virus antigens. The cells are expanded and stored for future use (‘off-the-shelf’) in HLA matched patients.
PTLD are lymphomas that occur after a transplant. Many post-transplant lymphomas are related to infection with Epstein–Barr virus (EBV). The risk of PTLD developing after transplant depends on type of transplant: around 1 in 200 people who have had a donor bone marrow or stem cell transplant, between 1–3 in 100 people who have had a kidney or liver transplant, between 1–6 in 100 people who have had a heart or a heart-lung transplant & between 4–10 in 100 people who have had a lung transplant [1]
Epstein-Barr virus (EBV)-associated post transplant lymphoproliferative disorder (PTLD) - second-line after rituximab
Intravenous infusion

Further information

Yes

Trial or other data

Nov 21Top-line data reported from PIII ALLELE trial. An ORR, as measured by independent oncologic response adjudication (IORA) assessment, of 50% was observed, with an ORR of 50% in PTLD following SOT and 50% in PTLD following HCT, with a best overall response of Complete Response (CR; n=5, SOT; n=5, HCT) or Partial Response (PR; n=7, SOT; n=2, HCT). Overall, median time to response (TTR) was 1.1 months (0.7-4.7). Of 19 responders, 11 had a duration of response (DOR) lasting more than six months and median DOR has not been reached yet. One-year survival rate was 61.1% overall (57.4% for SOT, and 66.8% for HCT). Those who responded had a longer survival vs. non-responders, with a median overall survival not evaluable (95% CI: 16.4, NE) and 1-year survival rate of 89.2% (95% CI: 63.1, 97.2). Safety findings were consistent with previously published data, with no new signals. There were no reports of tumor flare reaction, and no confirmed evidence of graft versus host disease (GvHD), organ rejection, infusion reactions, or cytokine release syndrome (CRS) related to tab-cel. At ASH, Atara will present additional data on tab-cel including long term OS from PII and multi-center Expanded Access Protocol (EAP) studies in relapsed/refractory EBV+ PTLD showing median OS of 54.6 months in all patients and OS at two years reaching over 86% in responders whether patients experienced CR or PR [13].
Apr 21PIII ALLELE trial is now due to complete collection of primary outcome data in Jun 22 [10].
Mar 21Combined analysis of PII studies (NCT00002663, NCT01498484, NCT02822495) reported showing that tabelecleucel was generally well tolerated with no confirmed evidence for graft-versus-host disease, cytokine release syndrome or neurotoxicity. Efficacy data from the same analysis showed a 62% objective response rate which includes both partial and complete response rates with best overall response of CR (n=24) or PR (n=7). Two year survival rates of 81.6% and 85.7% and one year survival rates of 86.7% and 85.7% for patients with CR and PR, respectively [9].
Feb 21PIII MATCH trial completes [9].
Nov 20Atara initiated a tab-cel® PII multi-cohort study in Q3 2020 and expects to enrol the first patient in Q4 2020. This study is being initiated concurrently in the U.S. and the EU. The multi-cohort study is intended to enrich the evidence base with the goal of expanding the potential label for tab-cel® in both treatment-naïve and previously treated patients (in six populations, including four within Immunodeficiency-Associated Lymphoproliferative Diseases (IA-LPDs) and two in other EBV-associated diseases) [8].
Nov 20Atara has initiated Single Patient Use (SPU) programme in lymphoproliferative disorders [8].
Nov 20Atara announces interim efficacy and adverse events data from PIII ALLELE trial. An Interim Analysis of the tab-cel® ALLELE study showed a 50% objective response rate (ORR) to tab-cel® with independent oncologic and radiographic assessment (IORA) in patients with relapsed-refractory EBV+ PTLD following hematopoietic cell transplants (HCT) or solid organ transplants (SOT), that had reached at least six months follow-up after achieving a response. This ORR is consistent with previously published investigator assessed data. The tab-cel® safety profile is also consistent with previously published data, with no new safety signals [8].
Jan 20No UK trial sites in NCT03394365 (ALLELE)
Jan 20No UK trial sites in NCT03392142 (MATCH)
Jun 19MATCH and ALLELE list a primary completion date of November 2020 [5].
Dec 17Interim results from a multicenter expanded access protocol study for patients with EBV associated cancers were consistent with the tabelecleucel profile observed in the PII studies conducted at Memorial Sloan Kettering Cancer Center. The estimated one-year overall survival for the 12 treated patients with rituximab-refractory EBV+PTLD was 90.9% [95% CI 50.8 -98.7%]. The company plan to start PIII studies by the end of 2017 [3].
Dec 16Atara Bio is planning two PIII trials, MATCH and ALLELE, to assess the efficacy of EBV-specific T-cell therapy in patients with rituximab-refractory EBV-PTLD after HCT or solid organ transplant (SOT). Objective response rate is the primary endpoint of the trials. The MATCH trial will be an open label trial and will enroll approximately 35 patients. The ALLELE trial is designed to be a two cohort trial, with the first cohort enrolling patients who received rituximab monotherapy and the secod cohort with patients who received rituximab in combination with chemotherapy. Each cohort will enroll 35 patients [2].

Evidence based evaluations