Time to CAR T-cell Remedy Could Affect Outcomes for Sufferers With Relapsed/Refractory Massive B-cell Lymphoma in New CIBMTR Evaluation

Kite’s Manufacturing Time for Yescarta ® within the U.S. is Median of 7-Days from Begin of Cell Enrichment to Harvest, with an General 16-Day Turnaround Time (Leukapheresis to Product Launch) –

– CIBMTR Evaluation Finds Median ‘Vein-to-Vein’ Time (Leukapheresis to Infusion) in Actual World Setting is 27-Days for Yescarta within the U.S. –

– In Identical Evaluation, Shorter Vein-to-Vein Time Related to 60% Full Response Charge in Sufferers Handled with Yescarta at Median Comply with-Up of 24.2 Months –

Kite, a Gilead Firm (Nasdaq: GILD), at present introduced outcomes from {one of the} largest real-world analyses of sufferers who acquired CAR T-cell remedy assessing the affect of time from leukapheresis to infusion (“vein-to-vein” time) for Yescarta ^® (axicabtagene ciloleucel) in grownup sufferers with relapsed or refractory (R/R) massive B-cell lymphoma (LBCL). The evaluation reported shorter vein-to-vein instances related to improved outcomes in sufferers handled with Yescarta, adjusted for key prognostic components. Information have been introduced on December 11, through the 2022 American Society of Hematology (ASH) Annual Assembly & Exposition (Summary #3345).

“These real-world knowledge additional make clear the optimistic affect that shorter vein-to-vein time can have on affected person outcomes,” stated Frederick L. Locke, MD, Chair of the Division of Blood and Marrow Transplant and Mobile Immunotherapy at Moffitt Most cancers Heart. “Extra research should be performed to additional perceive the affect of vein-to-vein time on therapy outcomes within the context of different prognostic options reminiscent of requirement for bridging remedy and tumor burden. It can be crucial for each neighborhood oncologists in search of a CAR T seek the advice of and cell therapists to grasp the potential affect of misplaced time when in search of the very best CAR T outcome for his or her sufferers.”

Within the pivotal scientific trials of the three commercially accessible CAR T-cell therapies for LBCL, Yescarta has reported shorter median vein-to-vein wait instances from leukapheresis to infusion.

“Because the chief in cell remedy, it is vital that we perceive the entire components that may contribute to the very best outcomes for sufferers,” stated Chris McDonald, SVP, World Head of Technical Operations, Kite. “We’re persevering with to put money into technical advances to scale back instances even additional. I’m hopeful research like it will immediate enhancements within the well being care supply system to scale back misplaced time for sufferers main as much as apheresis.”

This new real-world use evaluation assessed Yescarta sufferers between October 2017 and August 2020 utilizing the Heart for Worldwide Blood and Marrow Transplant Analysis (CIBMTR) Analysis Database, the submit advertising registry of economic sufferers prescribed Yescarta. Amongst all sufferers within the evaluation (n=1,383 handled throughout 78 U.S. approved therapy facilities), the general median vein-to-vein time for Yescarta was 27 days, inclusive of apheresis, each pre- and post-manufacturing transport, manufacturing time, and hospital scheduling and readiness together with affected person pre-conditioning previous to receiving their CAR T therapy. Kite’s manufacturing time for Yescarta within the U.S. is a median of seven days from begin of cell enrichment to reap, with an total 16-day turnaround time (Leukapheresis to Product Launch).

Shorter vein-to-vein time from the identical evaluation was related to a good full response (CR) charge and total survival (OS). With a median follow-up of 24.2 months, for sufferers with lower than 28 days or 28-39 days of vein-to-vein time, CR charges have been 60% or 61%, respectively in distinction to a CR charge of fifty% amongst sufferers with vein-to-vein time of 40 or extra days. OS charge at 24 months was 53% amongst sufferers with vein-to-vein time as much as 39 days versus 38% amongst sufferers with 40 or extra days vein-to-vein time.

Related charges of Grade ≥3 cytokine launch syndrome (CRS), Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS), and extended neutropenia have been noticed no matter vein-to-vein time. Sufferers with shorter vein-to-vein time had diminished danger of thrombocytopenia. ICANS of any grade could also be larger amongst sufferers with vein-to-vein time lower than 28 days however most have been resolved by 21 days from onset no matter vein-to-vein time.

CAR T-cell therapies are one-time therapies individually made ranging from a affected person’s personal white blood cells, referred to as T-cells. The cells are eliminated by means of leukapheresis and despatched to Kite’s specialised manufacturing services the place they’re modified with a Chimeric Antigen Receptor (CAR). As soon as a person remedy is created for a affected person, the cells are fastidiously checked, preserved, packed and despatched again to the hospital to be infused again into the affected person. Over 11,000 sufferers have been handled with Kite’s CAR T-cell therapies globally by means of greater than 300 approved therapy facilities all over the world, together with 117 of the main most cancers hospitals within the U.S.

About LBCL

In the USA and globally, LBCL is the commonest kind of non-Hodgkin lymphoma (NHL). In the USA, greater than 18,000 persons are recognized with LBCL every year. About 30-40% of sufferers with LBCL will want second-line therapy, as their most cancers will both relapse (return) or develop into refractory (not reply) to preliminary therapy.

About Yescarta

Please see full US Prescribing Info , together with BOXED WARNING and Remedy Information.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the therapy of:

• Grownup sufferers with massive B-cell lymphoma that’s refractory to first-line chemoimmunotherapy or that relapses inside 12 months of first-line chemoimmunotherapy.
• Grownup sufferers with relapsed or refractory massive B-cell lymphoma after two or extra traces of systemic remedy, together with diffuse massive B-cell lymphoma (DLBCL) not in any other case specified, main mediastinal massive B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
  Limitations of Use: YESCARTA isn’t indicated for the therapy of sufferers with main central nervous system lymphoma.
• Grownup sufferers with relapsed or refractory follicular lymphoma (FL) after two or extra traces of systemic remedy. This indication is accredited underneath accelerated approval based mostly on the response charge. Continued approval for this indication could also be contingent upon verification and outline of scientific profit within the confirmatory trial(s).

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

• Cytokine Launch Syndrome (CRS), together with deadly or life-threatening reactions, occurred in sufferers receiving YESCARTA. Don’t administer YESCARTA to sufferers with energetic an infection or inflammatory problems. Deal with extreme or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Neurologic toxicities, together with deadly or life-threatening reactions, occurred in sufferers receiving YESCARTA, together with concurrently with CRS or after CRS decision. Monitor for neurologic toxicities after therapy with YESCARTA. Present supportive care and/or corticosteroids as wanted.
• YESCARTA is offered solely by means of a restricted program underneath a Threat Analysis and Mitigation Technique (REMS) referred to as the YESCARTA and TECARTUS REMS Program.

CYTOKINE RELEASE SYNDROME (CRS)

CRS, together with deadly or life-threatening reactions, occurred. CRS occurred in 90% (379/422) of sufferers with non-Hodgkin lymphoma (NHL), together with ≥ Grade 3 in 9%. CRS occurred in 93% (256/276) of sufferers with massive B-cell lymphoma (LBCL), together with ≥ Grade 3 in 9%. Amongst sufferers with LBCL who died after receiving YESCARTA, 4 had ongoing CRS occasions on the time of loss of life. For sufferers with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (vary: 1-12 days) and the median length was 7 days (vary: 2-58 days). For sufferers with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (vary: 1-10 days) and the median length was 7 days (vary: 2-43 days). CRS occurred in 84% (123/146) of sufferers with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, together with ≥ Grade 3 in 8%. Amongst sufferers with iNHL who died after receiving YESCARTA, 1 affected person had an ongoing CRS occasion on the time of loss of life. The median time to onset of CRS was 4 days (vary: 1-20 days) and the median length was 6 days (vary: 1-27 days) for sufferers with iNHL.

Key manifestations of CRS (≥ 10%) in all sufferers mixed included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Critical occasions that could be related to CRS embody cardiac arrhythmias (together with atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

The affect of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL sufferers in ZUMA-1. Amongst sufferers who acquired tocilizumab and/or corticosteroids for ongoing Grade 1 occasions, CRS occurred in 93% (38/41), together with 2% (1/41) with Grade 3 CRS; no sufferers skilled a Grade 4 or 5 occasion. The median time to onset of CRS was 2 days (vary: 1-8 days) and the median length of CRS was 7 days (vary: 2-16 days). Prophylactic therapy with corticosteroids was administered to a cohort of 39 sufferers for 3 days starting on the day of infusion of YESCARTA. Thirty-one of the 39 sufferers (79%) developed CRS and have been managed with tocilizumab and/or therapeutic doses of corticosteroids with no sufferers growing ≥ Grade 3 CRS. The median time to onset of CRS was 5 days (vary: 1-15 days) and the median length of CRS was 4 days (vary: 1-10 days). Though there isn’t any identified mechanistic rationalization, think about the chance and advantages of prophylactic corticosteroids within the context of pre-existing comorbidities for the person affected person and the potential for the chance of Grade 4 and extended neurologic toxicities.

Be sure that 2 doses of tocilizumab can be found previous to YESCARTA infusion. Monitor sufferers for indicators and signs of CRS no less than every day for 7 days on the licensed healthcare facility, and for 4 weeks thereafter. Counsel sufferers to hunt fast medical consideration ought to indicators or signs of CRS happen at any time. On the first signal of CRS, institute therapy with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES

Neurologic toxicities (together with immune effector cell-associated neurotoxicity syndrome) that have been deadly or life-threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all sufferers with NHL receiving YESCARTA, together with ≥ Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of sufferers with LBCL in ZUMA-1, together with ≥ Grade 3 in 31% and in 74% (124/168) of sufferers in ZUMA-7 together with ≥ Grade 3 in 25%. The median time to onset was 4 days (vary: 1-43 days) and the median length was 17 days for sufferers with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (vary: 1-133 days) and the median length was 15 days in sufferers with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of sufferers with iNHL, together with ≥ Grade 3 in 21%. The median time to onset was 6 days (vary: 1-79 days) and the median length was 16 days. Ninety-eight p.c of all neurologic toxicities in sufferers with LBCL and 99% of all neurologic toxicities in sufferers with iNHL occurred throughout the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred throughout the first 7 days of infusion for 87% of affected sufferers with LBCL and 74% of affected sufferers with iNHL.

The most typical neurologic toxicities (≥ 10%) in all sufferers mixed included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Extended encephalopathy lasting as much as 173 days was famous. Critical occasions, together with aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Deadly and critical instances of cerebral edema and encephalopathy, together with late-onset encephalopathy, have occurred.

The affect of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL sufferers in ZUMA-1. Amongst sufferers who acquired corticosteroids on the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41), and 20% (8/41) had Grade 3 neurologic toxicities; no sufferers skilled a Grade 4 or 5 occasion. The median time to onset of neurologic toxicities was 6 days (vary: 1-93 days) with a median length of 8 days (vary: 1-144 days). Prophylactic therapy with corticosteroids was administered to a cohort of 39 sufferers for 3 days starting on the day of infusion of YESCARTA. Of these sufferers, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (vary: 1-274 days) with a median length of 12 days (vary: 1-107 days). Prophylactic corticosteroids for administration of CRS and neurologic toxicities might lead to a better grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset of and reduce the length of CRS.

Monitor sufferers for indicators and signs of neurologic toxicities no less than every day for 7 days on the licensed healthcare facility, and for 4 weeks thereafter, and deal with promptly.

REMS

Due to the chance of CRS and neurologic toxicities, YESCARTA is offered solely by means of a restricted program referred to as the YESCARTA and TECARTUS REMS Program which requires that: Healthcare services that dispense and administer YESCARTA should be enrolled and adjust to the REMS necessities and should have on-site, fast entry to a minimal of two doses of tocilizumab for every affected person for infusion inside 2 hours after YESCARTA infusion, if wanted for therapy of CRS. Licensed healthcare services should be certain that healthcare suppliers who prescribe, dispense, or administer YESCARTA are skilled within the administration of CRS and neurologic toxicities. Additional data is offered at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS

Allergic reactions, together with critical hypersensitivity reactions or anaphylaxis, might happen with the infusion of YESCARTA.

SERIOUS INFECTIONS

Extreme or life-threatening infections occurred. Infections (all grades) occurred in 45% of sufferers with NHL; ≥ Grade 3 infections occurred in 17% of sufferers, together with ≥ Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA shouldn’t be administered to sufferers with clinically vital energetic systemic infections. Monitor sufferers for indicators and signs of an infection earlier than and after infusion and deal with appropriately. Administer prophylactic antimicrobials in line with native pointers.

Febrile neutropenia was noticed in 36% of all sufferers with NHL and could also be concurrent with CRS. Within the occasion of febrile neutropenia, consider for an infection and handle with broad-spectrum antibiotics, fluids, and different supportive care as medically indicated.

In immunosuppressed sufferers, together with those that have acquired YESCARTA, life-threatening and deadly opportunistic infections together with disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The opportunity of HHV-6 encephalitis and PML must be thought-about in immunosuppressed sufferers with neurologic occasions and acceptable diagnostic evaluations must be carried out.

Hepatitis B virus (HBV) reactivation, in some instances leading to fulminant hepatitis, hepatic failure, and loss of life, can happen in sufferers handled with medicine directed in opposition to B cells, together with YESCARTA. Carry out screening for HBV, HCV, and HIV in accordance with scientific pointers earlier than assortment of cells for manufacturing.

PROLONGED CYTOPENIAS

Sufferers might exhibit cytopenias for a number of weeks following lymphodepleting chemotherapy and YESCARTA infusion. ≥ Grade 3 cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all sufferers with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can happen. Hypogammaglobulinemia was reported as an hostile response in 14% of all sufferers with NHL. Monitor immunoglobulin ranges after therapy and handle utilizing an infection precautions, antibiotic prophylaxis, and immunoglobulin alternative. The security of immunization with stay viral vaccines throughout or following YESCARTA therapy has not been studied. Vaccination with stay virus vaccines isn’t really helpful for no less than 6 weeks previous to the beginning of lymphodepleting chemotherapy, throughout YESCARTA therapy, and till immune restoration following therapy.

SECONDARY MALIGNANCIES

Secondary malignancies might develop. Monitor life-long for secondary malignancies. Within the occasion that one happens, contact Kite at 1-844-454-KITE (5483) to acquire directions on affected person samples to gather for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Because of the potential for neurologic occasions, together with altered psychological standing or seizures, sufferers are in danger for altered or decreased consciousness or coordination within the 8 weeks following YESCARTA infusion. Advise sufferers to chorus from driving and fascinating in hazardous occupations or actions, reminiscent of working heavy or probably harmful equipment, throughout this preliminary interval.

ADVERSE REACTIONS

The most typical non-laboratory hostile reactions (incidence ≥ 20%) in sufferers with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal ache, nausea, febrile neutropenia, chills, cough, an infection with an unspecified pathogen, dizziness, tremor, decreased urge for food, edema, hypoxia, stomach ache, aphasia, constipation, and vomiting.

The most typical hostile reactions (incidence ≥ 20%) in sufferers with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased urge for food, chills, diarrhea, febrile neutropenia, infections with an unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

The most typical non-laboratory hostile reactions (incidence ≥ 20%) in sufferers with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with an unspecified, tachycardia, febrile neutropenia, musculoskeletal ache, nausea, tremor, chills, diarrhea, constipation, decreased urge for food, cough, vomiting, hypoxia, arrhythmia, and dizziness.

In regards to the CIBMTR

The Heart for Worldwide Blood and Marrow Transplant Analysis is a nonprofit analysis collaboration between the Nationwide Marrow Donor Program (NMDP)/Be The Match, in Minneapolis, and the Medical School of Wisconsin, in Milwaukee. The CIBMTR collaborates with the worldwide scientific neighborhood to extend survival and enrich high quality of life for sufferers. The CIBMTR facilitates crucial observational and interventional analysis by means of scientific and statistical experience, a big community of facilities, and a novel database of long-term scientific knowledge for greater than 600,000 individuals who have acquired hematopoietic cell transplantation and different mobile therapies. Be taught extra at cibmtr.org.

About Kite

Kite, a Gilead Firm, is a worldwide biopharmaceutical firm based mostly in Santa Monica, California, centered on cell remedy to deal with and probably remedy most cancers. As the worldwide cell remedy chief, Kite has handled extra sufferers with CAR T-cell remedy than another firm. Kite has the biggest in-house cell remedy manufacturing community on this planet, spanning course of growth, vector manufacturing, scientific trial manufacturing and industrial product manufacturing. For extra data on Kite, please go to www.kitepharma.com .

About Gilead Sciences

Gilead Sciences, Inc. is a biopharmaceutical firm that has pursued and achieved breakthroughs in medication for greater than three many years, with the purpose of making a more healthy world for all folks. The corporate is dedicated to advancing revolutionary medicines to stop and deal with life-threatening ailments, together with HIV, viral hepatitis and most cancers. Gilead operates in additional than 35 international locations worldwide, with headquarters in Foster Metropolis, California.

Ahead-Trying Statements

This press launch consists of forward-looking statements throughout the which means of the Non-public Securities Litigation Reform Act of 1995 which can be topic to dangers, uncertainties and different components, together with Kite’s potential to extend its CAR T-cell remedy manufacturing capability, well timed manufacture and ship such therapies or produce an quantity of provide adequate to fulfill demand for such therapies; Kite’s potential to provoke, progress or full scientific trials inside presently anticipated timelines or in any respect; the potential for unfavorable outcomes from ongoing or extra scientific trials; Kite’s potential to obtain regulatory approvals in a well timed method or in any respect, and the chance that any such approvals could also be topic to vital limitations on use; the chance that CAR T-cell remedy won’t be broadly accepted by physicians, sufferers, hospitals, most cancers therapy facilities, payers and others within the medical neighborhood; and any assumptions underlying any of the foregoing. These and different dangers, uncertainties and different components are described intimately in Gilead’s Quarterly Report on Kind 10-Q for the quarter ended September 20, 2022 as filed with the U.S. Securities and Trade Fee. These dangers, uncertainties and different components might trigger precise outcomes to vary materially from these referred to within the forward-looking statements. All statements aside from statements of historic truth are statements that may very well be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements aren’t ensures of future efficiency and contain dangers and uncertainties and is cautioned to not place undue reliance on these forward-looking statements. All forward-looking statements are based mostly on data presently accessible to Gilead and Kite and Gilead and Kite assume no obligation and disclaim any intent to replace any such forward-looking statements.

U.S. Prescribing Info for Yescarta together with BOXED WARNING is offered at www.kitepharma.com and www.gilead.com .