Juli 25, 2021: Kite, ett Gilead Company (Nasdaq: GILD), meddelade idag att FDA har beviljat TecartusTM (brexucabtagene autoleucel, tidigare KTE-X19), den första och enda godkända chimär antigenreceptor CAR T-cellsterapi for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, accelerated approval (MCL). The FDA granted priority review and breakthrough therapy designation to this one-time therapy, which was based on the results of ZUMA-2, a single-arm, open-label study in which 87 percent of patients responded to a single infusion of Tecartus, with 62 percent achieving a complete response (CR). 18% of patients who were evaluated for safety had cytokinfrisättningssyndrom (CRS) of Grade 3 or higher, and 37% had neurologic toxicities of Grade 3 or higher.
“Despite promising advances, there are still significant gaps in treatment for MCL patients who progress after initial therapy,” said Michael Wang, MD, ZUMA-2 Lead Investigator and Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center. “Many patients have high-risk disease, which means they are more likely to progress despite treatment. “Tecartus is the first cell therapy available to people with relapsed or refractory MCL. It has an impressive response rate of nearly 90% and early clinical evidence suggests that remissions may last through later lines of therapy. This makes it an important choice for these patients.”
"Vi är stolta över att lansera vår andra cellterapi eftersom Kite har åtagit sig att ge löftet om CAR T-terapi to patients with haematological cancers,” said Christi Shaw, Kite’s Chief Executive Officer. “I would like to express my gratitude to the patient study participants, caregivers, clinical researchers, regulators, and dedicated Kite colleagues who contributed to this approval, and we look forward to working with the lymfom community to bring this potentially transformative therapy to patients with relapsed or refractory MCL.”
Tecartus’ product label includes a boxed warning about the risks of CRS and neurologic toxicities. The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Tecartus, which has been combined with the REMS for Yescarta® (axicabtagene ciloleucel). The REMS programme will inform and educate healthcare professionals about the risks associated with Tecartus therapy, and training and certification in the REMS programme will be a requirement for centres offering Tecartus therapy to receive final authorization.
MCL is a rare type of icke-Hodgkin-lymfom (NHL) that develops from cells in the lymph node’s “mantle zone” and primarily affects men over the age of 60. Following a relapse, MCL is extremely aggressive, and many patients progress after treatment.
The Lymphoma Research Foundation’s Chief Executive Officer, Meghan Gutierrez, said, “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.” “Researchers have made significant progress in our understanding of this disease over the last decade, and we’ve seen an increase in patient clinical trials, which we hope will continue to improve treatment strategies and options for people with mantle cell lymphoma. Today’s news builds on that progress and gives mantelcell patients and their families reason to be hopeful.”
Kite’s commercial manufacturing facility in El Segundo, California, will produce Tecartus. Kite achieved a 96 percent manufacturing success rate in the ZUMA-2 trial, with a median manufacturing turnaround time of 15 days from leukapheresis to product delivery. Patients with advanced disease, who are severely ill and at risk of rapid progression, require manufacturing speed in particular.
Kite Konnect®, en integrerad teknologiplattform som ger information och assistans genom hela terapiprocessen för Kites kommersialiserade CAR T-terapier, inklusive kurirspårning för försändelser och uppdateringar av tillverkningsstatus, är tillgängligt för patienter vars vårdpersonal har ordinerat Tecartus-terapi. Kite Konnect är ett stödsystem för patienter som får Yescarta eller Tecartus, samt information till de vårdteam som stödjer dem.
KTE-X19 utvärderas för närvarande i EU, och den europeiska läkemedelsmyndigheten har beviljat den Priority Medicines (PRIME) beteckning för recidiverande eller refraktär MCL.
Resultat av Tecartus-försöket
Godkännandet av Tecartus är baserat på resultat från den pågående pivotala studien ZUMA-2, som är en enarms, öppen studie. 74 vuxna patienter med recidiverande eller refraktär MCL som tidigare hade fått antracyklin- eller bendamustin-innehållande kemoterapi, anti-CD20-antikroppsbehandling eller en Bruton-tyrosinkinashämmare inkluderades i studien (ibrutinib eller acalabrutinib). Det primära effektmåttet var den objektiva svarsfrekvensen (ORR), som definierades som den kombinerade frekvensen av CR och partiella svar enligt bedömningen av en oberoende radiologisk granskningskommitté enligt Lugano-klassificeringen (2014). (IRRC).
I forskningen reagerade 87 procent av patienterna (n=60 som kan utvärderas för effektanalys) på en enda Tecartus-infusion, med 62 procent som uppnådde ett fullständigt svar. Uppföljningen var minst sex månader efter det första objektiva sjukdomssvaret för alla patienter. Medianreaktionstiden har ännu inte fastställts.
In the experiment, 18% of patients (n=82 evaluable for safety) had Grade 3 or higher CRS, while 37% of patients had neurologic problems. Anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unclear, pneumonia, hypocalcemia, and lymphopenia were the most prevalent Grade 3 or higher adverse effects (10%). With a Risk Evaluation and Mitigation Strategy, the FDA approved Tecartus (REMS). The Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program has been integrated with the Tecartus REMS and is now known as the “Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program”
Om Tecartus
Tecartus är en autolog anti-CD19 CAR T-cellsterapi. Tecartus använder XLP™ manufacturing process that includes T cell enrichment, a necessary step in certain B-cell malignancies in which circulating lymphoblasts are a common feature. In addition to MCL, Tecartus is also currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL) and kronisk lymfocytisk leukemi (CLL). The use of Tecartus in ALL and CLL is investigational, and its safety and efficacy have not been established in these cancer types.
Tecartus Indikation
Tecartus är en CD19-riktad genetiskt modifierad autolog T-cellsimmunterapi indicerad för behandling av vuxna patienter med återfall eller refraktärt mantelcellslymfom (MCL).
Denna indikation är godkänd under accelererat godkännande baserat på den totala svarsfrekvensen och svarets hållbarhet. Fortsatt godkännande för denna indikation kan vara beroende av verifiering och beskrivning av klinisk nytta i en bekräftande studie.
