REAL-WORLD RESULTS DEMONSTRATE HIGH RESPONSE RATE AND DURABLE REMISSION WITH KITE CAR T-CELL THERAPIES FOR R/R MCL AND FL AT EHA 2023

– Data Presented Confirm High Response Rates for Axicabtagene Ciloleucel and Brexucabtagene Autoleucel in Difficult-To-Treat Blood Cancers, Consistent With Clinical Studies – 

Stockley Park, UK – Kite, a Gilead Company, today announced results from two real-world studies that support the use of Yescarta^® (axicabtagene ciloleucel) in relapsed/refractory (R/R) follicular lymphoma (FL) (abstract S223)[i] and Tecartus^® (brexucabtagene autoleucel) in R/R mantle cell lymphoma (MCL) (abstract 220)[ii]. The results are presented at the European Hematology Association (EHA) 2023 Annual Congress in Frankfurt, Germany.

“The breadth of data presented by Kite at EHA 2023 reaffirms our commitment to research that shows how CAR T cell therapy is used in clinical and real-world settings,” said Dick Sundh, Vice President, Head of Australia, Canada, and Europe (ACE), Kite. “At Kite, we are committed to increasing confidence in the durability and reliability of CAR T-cell therapies for haematologic malignancies.” 

Abstract #S223: Real-world early outcomes of axicabtagene ciloleucel for relapsed or refractory follicular lymphoma

Real-world analysis of R/R FL patients treated with axicabtagene ciloleucel, using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, showed that objective response rate (ORR) and complete response rates (CR) were 93% (95% CI 88-97%) and 84% (95% CI 77-89%), respectively, and were similar to ZUMA-5 results. ^1,[iii],[iv] Patients had a median of 4 (range 1-13) lines of prior therapy, including 14% who also underwent prior autologous stem cell transplantation. Ninety-two patients (40%) would have been ineligible for ZUMA-5, mainly due to comorbidities. Estimated progression free survival (PFS) and overall survival (OS) at 6 months were 88% (95% CI 81-92%) and 96% (95% CI 91-98%), respectively, and were comparable regardless of ZUMA-5 eligibility.  Grade ≥3 cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2% (95% CI 0-6%) and 13% (95% CI 8-19%) of patients, respectively.¹

“This is the first report on axicabtagene ciloleucel to treat relapsed and refractory follicular lymphoma in real-world settings, and the outcomes are consistent with those observed in the ZUMA-5 trial,” said Dominique Tonelli, Executive Director, Head of Medical Affairs, ACE at Kite. “We are encouraged that these findings support ongoing broad use in these patients, and we will continue to examine outcomes with longer follow-up.”

Abstract #220: Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory mantle cell lymphoma: A CIBMTR subgroup analysis by prior treatment

Prospective data from 380 patients with R/R MCL from the CIBMTR observational database demonstrated an ORR of 90%, similar to ZUMA-2 results, and a high CR (78%) in patients who received brexucabtagene autoleucel in the US, regardless of type of prior treatment, including: Bruton's tyrosine kinase inhibitor (BTKi), bendamustine or autologous hematopoietic cell transplant (autoHCT), with 12 months follow up. Additionally, at 12 months, duration of response (DOR) (since earliest CR/PR), PFS and OS rates were 64%, 61% and 74% respectively. Grade ≥3 CRS and ICANS (based on American Society for Transplantation and Cellular Therapy [ASTCT] criteria) incidence were 10% and 28% respectively. Most CRS (95%) and ICANS (78%) resolved within 3 weeks since onset.²

In a multivariate analysis of patients who received brexucabtagene autoleucel in earlier lines of therapy (1-2 vs ≥ 3 prior lines of therapy), the data showed an ORR of 94% and a CR of 88%. The multivariate analysis assessed outcomes based on prior therapy; findings show that real-world effectiveness and safety outcomes with brexucabtagene autoleucel in patients with R/R MCL are consistent regardless of prior treatment (including prior BTKi, bendamustine or ASCT). In BTKi-naïve patients, effectiveness (ORR 92%, CR 83%) and safety outcomes are consistent when compared with prior BTKi-treated patients. In patients with prior bendamustine use, effectiveness remained consistent and prior bendamustine use was associated with a reduced risk of Grade ≥3 ICANS (odds ratio [OR] 0.50; 95% confidence interval [CI], 0.30–0.84) and increased risk of prolonged thrombocytopenia (OR 1.98; 95% CI, 1.11–3.53). Within the multivariate analysis, PFS was improved in patients with prior autoHCT compared to those without prior autoHCT (hazard ratio [HR] 0.56; 95% CI, 0.35–0.88). ²

“Unfortunately for patients living with mantle cell lymphoma, outcomes are poor and there are limited treatment options,” said Frank Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical Development. “Data from this real-world registry suggest that earlier treatment with brexucabtagene autoleucel may confer better outcomes in these difficult-to-treat patients compared to later lines and should be evaluated further in additional studies.”

About CIBMTR

The Center for International Blood and Marrow Transplant Research is a nonprofit research collaboration between the NMDP/Be The Match, in Minneapolis, and the Medical College of Wisconsin, in Milwaukee. CIBMTR collaborates with the global scientific community to increase survival and enrich quality of life for patients. CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of centres, and a unique database of long-term clinical data for more than 635,000 people who have received hematopoietic cell transplantation and other cellular therapies.

About ZUMA-5

ZUMA-5 is an ongoing, single-arm, open-label, international, multicentre trial evaluating 122 patients (≥18 years old) with relapsed or refractory follicular lymphoma (FL), who received at least two prior lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. The primary endpoint was ORR, and secondary endpoints included CR rate, ORR and CR in patients who had received three or more lines of prior therapy, DoR, overall survival, progression-free survival and incidence of adverse events.^3,4

 

About ZUMA-2

ZUMA-2 is a single-arm, multicentre, open-label Phase 2 trial of 74 enrolled/leukapheresed adult patients (≥18 years old) with R/R MCL following up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy and the BTK inhibitors ibrutinib or acalabrutinib. The objectives are to evaluate the efficacy (60 patients) and safety (68 patients) after a single infusion of brexucabtagene autoleucel. The primary endpoint is objective response rate defined as the combined rate of complete responses and partial responses assessed by an Independent Radiology Review Committee. Secondary endpoints include duration of response, best objective response, progression-free survival, overall survival and incidence of adverse events.[v]

 

About Follicular Lymphoma (FL) 
Follicular lymphoma (FL) is a form of indolent non-Hodgkin lymphoma (iNHL) in which malignant tumours slowly grow but can become more aggressive over time, especially if they relapse. FL is the most common form of indolent non-Hodgkin lymphoma and the second most common type of lymphoma globally. It accounts for approximately 22% of all lymphomas diagnosed worldwide.[vi]^,[vii]  Currently, there are limited options for the treatment of relapsed or refractory FL after two or more lines of therapy. 

 

About Mantle Cell Lymphoma (MCL) 

Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the “mantle zone” of the lymph node and predominantly affects men over the age of 60.[viii]^,[ix] Approximately 33,000 people worldwide are diagnosed with MCL each year including 7,400 in Europe.[x]^{,[xi],[xii],[xiii]} MCL is highly aggressive following relapse, with many patients progressing following therapy.[xiv] 

 

About Axicabtagene Ciloleucel

Axicabtagene ciloleucel is a chimeric antigen receptor (CAR) T-cell therapy, approved by the European Commission (EC) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) who relapse within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy;^[xv] adult patients with relapsed or refractory follicular lymphoma (FL) after three or more lines of systemic therapy; adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B cell lymphoma (PMBCL), after two or more lines of systemic therapy.¹⁵

 

About Brexucabtagene Autoleucel

Brexucabtagene autoleucel is a chimeric antigen receptor (CAR) T-cell therapy, approved by the European Commission (EC) for the treatment of adult patients withrelapsed or refractory mantle cell lymphoma after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor, and for the treatment of adult patients 26 years of age and above with relapsed or refractory
B-cell precursor acute lymphoblastic leukaemia.[xvi] 

About Kite 

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and potentially cure cancer.  As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company.  Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial production and commercial product manufacturing.

About Gilead Sciences 

Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Gilead Sciences acquired Kite in 2017.

Forward-Looking Statements

This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavourable results from ongoing or additional clinical studies, including those involving axicabtagene ciloleucel and brexucabtagene autoleucel; the possibility that Gilead and Kite may make a strategic decision to discontinue development of these programmes and, as a result, these programmes may never be successfully commercialised for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.

[i] Jacobson C, et al. Real-world Early Outcomes of Axicabtagene Ciloleucel for Relapsed or Refractory Follicular Lymphoma. Abstract #S223 presented at the European Hematology Association (EHA) 2023 Annual Congress.

[ii] Ahmed N, et al. Real-World Outcomes of Brexucabtagene Autoleucel (brexu-cel) for Relapsed or Refractory Mantle Cell Lymphoma: A CIBMTR Subgroup Analysis by Prior Treatment. Abstract #220 presented at the European Hematology Association (EHA) 2023 Annual Congress.

[iii] ClinicalTrials.gov. A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5). Available at: https://clinicaltrials.gov/ct2/show/NCT03105336 Accessed: June 2023.

[iv] Neelapu S. et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec; 377(26):2531-2544.

[v] ClinicalTrials.gov Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2) (ZUMA-2). Available at: https://clinicaltrials.gov/ct2/show/NCT02601313 Accessed: June 2023.

[vi] Follicular Lymphoma Foundation. What is FL? Available at: https://www.theflf.org/what-is-fl. Accessed June 2023.

[vii] The Non-Hodgkin's Lymphoma Classification Project. A Clinical Evaluation of the International Lymphoma Study Group Classification of Non-Hodgkin's Lymphoma. Blood (1997) 89 (11): 3909–3918.

[viii] Dreyling M, Campo E, Hermine O, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2017 July; 28 (4): iv62-iv71.

[ix] Sharma S & Sweetenham J. Mantle Cell Lymphoma: Are New Therapies Changing the Standard of Care? EMJ Oncol. 2018;6{1}:109-119.

[x] NORD. Mantle Cell Lymphoma. https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/. Accessed June 2023.

[xi] Leukemia & Lymphoma Society. NHL subtypes. Available at: https://www.lls.org/lymphoma/non-hodgkin-lymphoma/diagnosis/nhl-subtypes. Accessed: June 2023.

[xii] Globocan 2020. Europe fact sheet. Available at https://gco.iarc.fr/today/data/factsheets/populations/908-europe-fact-sheets.pdf Accessed: June 2023.

[xiii] Ferlay J, Colombet, M., Soerjomataram, I., et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. European Journal Of Cancer, 2018;103, 356-387. Available at: https://doi.org/10.1016/j.ejca.2018.07.005. Accessed: June 2023.

[xiv] Wang M, et al. KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020;382:1331-1342.

^[xv] European Medicines Agency. Yescarta^® (axicabtagene ciloleucel) SPC. Available at: https://www.ema.europa.eu/documents/product-information/yescarta-epar-product-information_en.pdf. Accessed: June 2023.

[xvi] European Medicines Agency. Tecartus® (autologous anti-CD19-transduced CD3+ cells) SPC. Available at: https://www.ema.europa.eu/en/documents/product-information/tecartus-epar-product-information_en.pdf.  Accessed: June 2023.