On December 6, 2025 Protagonist Therapeutics, Inc. ("Protagonist") (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) reported that new 52-week results from the pivotal Phase 3 VERIFY study evaluating rusfertide in patients with polycythemia vera (PV) will be presented in an oral presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. These findings further reinforce rusfertide’s efficacy and safety and demonstrate durability of response, with 61.9% of patients continuously treated with rusfertide maintaining absence of phlebotomy eligibility from baseline to Week 52.

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"The 52-week data demonstrated the sustained efficacy of rusfertide, reducing the need for patients to receive phlebotomy while maintaining hematocrit control," said Dr. Andrew T. Kuykendall, M.D., VERIFY Lead Investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. "The 32-week VERIFY primary results were already promising, and this deeper understanding of the durability of response with rusfertide is critical to inform clinical decision-making for polycythemia vera. In totality, these findings, including the long-term extension data from THRIVE, reaffirm rusfertide as a potential new addition to the standard of care for patients with PV."

Achieving and maintaining controlled hematocrit (HCT) levels of <45% is the primary treatment goal in PV to prevent thrombotic events and help alleviate symptoms. However, many patients still experience uncontrolled hematocrit levels and burdensome symptoms with current standard of care treatments. The VERIFY study, designed to evaluate the efficacy and safety of rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite receiving current standard of care treatment, met the primary endpoint and all four key secondary endpoints in its previously-reported 32-week primary analysis. During Part 1a (Weeks 0-32) of the VERIFY study, 293 patients were randomized to receive either rusfertide (147 patients) or placebo (146 patients), as an add-on to their current treatment. During Part 1b (Weeks 32-52), all participants were eligible to receive open-label rusfertide to evaluate the durability of the treatment response. 274 patients (94%) continued into Part 1b, and 267 patients (91%) remained in the study through Week 52, with 254 continuing to receive rusfertide in Part 2 (Weeks 52-156).

Key findings at 52 Weeks include1,2:

Phlebotomy Eligibility

61.9% of patients treated with rusfertide plus current standard of care throughout Parts 1a and 1b of the study experienced a durable clinical response, defined as absence of phlebotomy eligibility.
84.1% of patients treated with rusfertide who experienced a clinical response in the Part 1a assessment window (Weeks 20-32) maintained their response.
77.9% of patients who crossed over from placebo to rusfertide at Week 32 for Part 1b experienced a clinical response during the Part 1b assessment window (Weeks 40-52).
Median time to first phlebotomy was 16 Weeks in the placebo group, while median time to first phlebotomy was not reached in either the rusfertide group in Part 1a or 1b, or the placebo to rusfertide crossover group in Part 1b.
HCT Control

Mean hematocrit remained <43% through Week 52 in patients treated with rusfertide throughout Part 1a and Part 1b and those who switched from placebo to rusfertide for Part 1b.
Median time to first hematocrit ≥ 45% was 8.3 Weeks in the placebo group in Part 1a, while median time to first hematocrit ≥ 45% was not reached in the rusfertide group during Parts 1a or 1b.
Quality of Life Endpoints

Patients treated with rusfertide in Parts 1a and 1b maintained improvements in patient reported outcomes as measured by PROMIS Fatigue SF-8a and MFSAF TSS7.
Rusfertide was generally well-tolerated through 52 Weeks of treatment. The most common treatment-emergent adverse events (AE) in rusfertide-treated patients were injection site reactions (47.4%), anemia (25.6%) and fatigue (19.6%), which were primarily grade 1 or 2. Serious AEs occurred in 8.1% of overall rusfertide-treated patients.

The durability of response and safety profile of rusfertide in patients with PV from the 52-week VERIFY data are further supported by the four-year analysis of 46 patients who continued from REVIVE to the long-term extension study, THRIVE.

The results show that after transitioning to THRIVE, continued treatment with rusfertide with or without cytoreductive therapy demonstrated consistent, long-term hematocrit control with a greater than 13-fold reduction in estimated annual therapeutic phlebotomy rate compared to baseline prior to study entry in REVIVE. Prior to study entry in REVIVE, the mean annualized phlebotomy rate (i.e., phlebotomy/year) for the 46 patients who eventually rolled over to THRIVE was 9.2 phlebotomies/year. The mean annualized phlebotomy rate during THRIVE was 0.7 phlebotomies/year.3 Rusfertide’s safety profile was consistent with prior observations.

"The totality of these data further demonstrates rusfertide’s well tolerated safety profile and ability to deliver durable hematocrit control and clinical response as defined by absence of phlebotomy eligibility and support its potential to expand the treatment armamentarium for PV and positively impact the lives of patients with PV," said Arturo Molina, M.D., M.S., Chief Medical Officer at Protagonist. "We look forward to continuing to work with our partner, Takeda, to prepare for submission of an NDA to the FDA."

"We are committed to making a difference for patients with PV who face serious risks from thrombotic events if they are unable to adequately control hematocrit levels with currently available treatment options," said Phuong Khanh (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit at Takeda. "The comprehensive data presented at ASH (Free ASH Whitepaper), from the pivotal VERIFY and long-term THRIVE studies, strongly underscore the potential of rusfertide to provide a sustained response, addressing a critical unmet need in managing this chronic cancer. We are excited to advance rusfertide towards regulatory approval in collaboration with Protagonist, bringing us one step closer to improving the care of patients suffering from PV."

Rusfertide has received Breakthrough Therapy Designation, Orphan Drug Designation and Fast Track Designation from the U.S. Food & Drug Administration (FDA).

About VERIFY
The Phase 3 VERIFY study (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period, with treatment extension for participants who are continuing to derive benefit from rusfertide beyond the 156-week treatment period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment, which could include hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during Weeks 20-32, which was defined as the absence of "phlebotomy eligibility." To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%.

All patients have completed their participation in the randomized, placebo-controlled portion of the study evaluating the efficacy and safety of rusfertide plus current standard of care versus placebo plus current standard of care and are now in the open-label portions of the study.

About THRIVE
The THRIVE study (NCT06033586) is an ongoing, open-label extension study evaluating the long-term durability of response and safety profile of rusfertide in patients with polycythemia vera. The study includes 46 patients who previously participated in the Phase 2 REVIVE study (NCT04057040). Patients eligible to transition to the THRIVE study completed the open-label extension portion of REVIVE, ≥12 months of rusfertide therapy and had an end-of-treatment visit. THRIVE is designed to further assess the maintenance of hematocrit control, reduction in the need for therapeutic phlebotomy and overall safety of once-weekly, subcutaneous rusfertide over an additional two-year treatment period.

About Polycythemia Vera (PV)
Polycythemia vera (PV) is characterized by the overproduction of red blood cells (erythrocytosis), which increases blood viscosity, or thickness, that can result in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. Hematocrit (HCT) is the ratio of red blood cells to total amount of blood in the body. Achieving and maintaining controlled HCT levels of <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus.

(Press release, Takeda, DEC 6, 2025, View Source [SID1234661226])

On December 6, 2025 Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company, reported new data from a post hoc analysis of the Phase 2 eNRGy trial (NCT02912949) evaluating zenocutuzumab in patients with treatment-naïve non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion. Results were presented in a late-breaking oral session at the IASLC-ASCO North America Conference on Lung Cancer (NACLC), in Chicago, Illinois.

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The new analysis evaluated the efficacy and safety of zenocutuzumab-zbco in treatment-naïve and previously treated NRG1+ NSCLC. Among 20 treatment-naïve and 121 previously treated patients, zenocutuzumab demonstrated an overall response rate (ORR) of 35% and 31%, respectively. The clinical benefit rate, defined as partial/complete response or stable disease for ≥24 weeks, was 65% in treatment-naïve and 58% in previously treated patients. Median duration of response was 17.1 months in treatment naïve patients, notably longer than in previously treated patients, 7.4 months. All treatment-related adverse events were grade 1 or 2. Zenocutuzumab safety profile was favorable and consistent with prior data.

"These data underscore the potential of zenocutuzumab as a first-line option for patients with NRG1-positive NSCLC, a patient population that typically responds poorly to standard first-line therapy," said Stephen Liu, MD, of Georgetown University. "Early and durable responses, coupled with a favorable safety profile are encouraging and highlight the importance of targeted therapy in this rare molecular subset."

"Consistent with other therapies targeting key oncogenic drivers, early intervention can lead to better outcomes — and we see the same with zenocutuzumab," said Pritesh J. Gandhi, Chief Development Officer at Partner Therapeutics. "These findings strengthen our conviction that early targeted inhibition of the NRG1 pathway with zenocutuzumab has the potential to meaningfully improve outcomes for patients with NRG1+ NSCLC."

"For patients and families facing NRG1+ lung cancer, these results mark meaningful progress," said Danielle Hicks, Chief Patient Officer of GO2 for Lung Cancer. "The durable responses and manageable safety profile of zenocutuzumab offer renewed hope and reinforce the need for continued innovation in biomarker-driven lung cancer care."

The abstract will be available on the Partner Therapeutics website under the research tab following the conference. Additional meeting information can be found on the IASLC-ASCO NACLC website.

In December 2024, zenocutuzumab-zbco (BIZENGRI) received U.S. Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The indications were approved under accelerated approval based on ORR and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.

About NRG1 Gene Fusions

NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably tissue-based RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1.

About BIZENGRI (zenocutuzumab-zbco)

INDICATIONS

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

BOXED WARNING: EMBRYO-FETAL TOXICITY

Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.

WARNINGS AND PRECUATIONS

Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions

BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.

Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.

Interstitial Lung Disease/Pneumonitis

BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated.

Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed.

Left Ventricular Dysfunction

BIZENGRI can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.

Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI.

Embryo-Fetal Toxicity

Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.

ADVERSE REACTIONS

NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC

Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).

In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).

NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI.

There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).

Please see full Prescribing Information, including Boxed Warning

(Press release, Partner Therapeutics, DEC 6, 2025, View Source [SID1234661223])

On December 6, 2025 Johnson & Johnson (NYSE: JNJ) reported updated results from the Phase 3 CARTITUDE-4 study supporting durable treatment-free remissions as early as second line treatment with CARVYKTI (ciltacabtagene autoleucel; cilta-cel). In 80 percent of as-treated patients with relapsed or refractory multiple myeloma (RRMM) and standard-risk cytogenetics who were treated with CARVYKTI as early as first relapse, the disease did not progress and no further treatment was required at 2.5 years (30 months).1 These results add to the body of clinical and real-world experience established across more than 9,000 patients treated with CARVYKTI globally.1

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Additional translational analyses demonstrated that patients receiving CARVYKTI in earlier lines had improved immune fitness, which suggests a correlation with longer progression-free survival (PFS).1 These data (Abstracts #92, #94) were featured in oral presentations at the 2025 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

"These data suggest that a single infusion of CARVYKTI for standard-risk patients may provide additional benefit to patients as early as second line of therapy," said Luciano J. Costa, M.D., Ph.D.,* Professor of Medicine at the University of Alabama and principal investigator of the CARTITUDE-4 study. "Treating patients with multiple myeloma after first relapse offers the opportunity to achieve deeper and more durable responses, shifting the treatment paradigm closer to the possibility of long-term remission and, ultimately, cure."

"Our goal is to treat patients as early as possible, when they have the best chance for lasting remission," said Jordan Schecter, M.D., Vice President, Research & Development, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "With more than 9,000 patients treated globally, CARVYKTI has demonstrated robust efficacy as soon as first relapse and is the first and only CAR-T to significantly extend overall survival versus standard therapies."

In the analysis of CARTITUDE-4 data, 176 patients received CARVYKTI as early as second line and 59 of those patients had standard-risk cytogenetics.1 At a median follow-up of 33.6 months, the 30-month PFS rate among the standard-risk patients in the as-treated population appeared to plateau at 80.5 percent (95 percent CI, 67.2–88.8) following a single infusion of CARVYKTI.1 Notably, all 26 patients (100%) from this group who achieved minimal residual disease (MRD)-negative complete response at 12 months following CARVYKTI infusion remained progression-free at 30 months.1

Additionally, a translational analysis evaluated the relationship between immune biomarkers and PFS in patients treated with CARVYKTI in CARTITUDE-1 and CARTITUDE-4.2 Using CARVYKTI after one or two prior lines of therapy demonstrated stronger immune fitness versus patients with three or more prior lines of therapy, characterized by increased baseline CD4⁺ naïve T cells (a type of immune cell that has not encountered an antigen) in peripheral blood.2 Bone marrow tumor analyses from patients treated with CARVYKTI in CARTITUDE-4 also demonstrated a more immune-activated profile in patients treated after one prior line of therapy versus three.2 These biomarker data identify potential immunologic factors associated with longer PFS and support the improved survival outcomes exhibited with CARVYKTI for patients treated as early as second line.2

As CARVYKTI use has broadened across academic centers and community practices, Johnson & Johnson continues to collect and analyze clinical and real-world data to further characterize long-term remission outcomes and safety trends. This comprehensive experience across diverse patient populations provides an important foundation for expanding use into earlier treatment settings.

About the CARTITUDE-1 Study

CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study that evaluated the efficacy and safety of cilta-cel in adults with relapsed and/or refractory multiple myeloma (RRMM), 99 percent of whom were refractory to the last line of treatment; 88 percent of whom were triple-class refractory, meaning their cancer did not or no longer responds to an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.3

The primary objective of the Phase 1b portion of the study, involving 29 patients, was to characterize the safety and confirm the dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). Based on the safety profile observed in this portion of the study, outpatient dosing is being evaluated in additional CARTITUDE studies. The Phase 2 portion of the study is evaluating the efficacy of cilta-cel with overall response as the primary endpoint. The study involved patients with heavily pretreated RRMM who historically have an expected median PFS of <6 months and median overall survival of ~1 year.

About the CARTITUDE-4 Study

CARTITUDE-4 (NCT04181827) is the first randomized Phase 3 study evaluating the efficacy and safety of CARVYKTI. The study compares CARVYKTI with standard of care treatments PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. The primary endpoint of the study is PFS; safety, OS, minimal residual disease negative rate and overall response rate are secondary endpoints.

About CARVYKTI (ciltacabtagene autoleucel; cilta-cel)

CARVYKTI (cilta-cel) received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.4 In April 2024, CARVYKTI was approved as the first and only cell therapy in the U.S. for treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide. In April 2024, the European Medicines Agency (EMA) approved a Type II variation for CARVYKTI for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide.

CARVYKTI is a BCMA-directed, genetically modified autologous T-cell immunotherapy that involves reprogramming a patient’s own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR-positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI.

For more information, visit www.CARVYKTI.com.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.5 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.6 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.7 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.8 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.9 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.10,11

CARVYKTI IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE

CARVYKTI (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and
SECONDARY HEMATOLOGICAL MALIGNANCIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI. Do not administer CARVYKTI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI. Provide supportive care and/or corticosteroids as needed.

Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI.

Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI. HLH/MAS can occur with CRS or neurologic toxicities.

Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI.

Immune Effector Cell-associated Enterocolitis (IEC-EC), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI.

Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with CARVYKTI. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI.

WARNINGS AND PRECAUTIONS

Increased early mortality. In CARTITUDE-4, a (1:1) randomized controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the CARVYKTI arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI infusion, and 19 deaths occurred after CARVYKTI infusion. Of the 10 deaths that occurred prior to CARVYKTI infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after CARVYKTI infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12).

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI. Among patients receiving CARVYKTI for RRMM in the CARTITUDE-1 & -4 studies (N=285), CRS occurred in 84% (238/285), including ≥ Grade 3 CRS (ASTCT 2019) in 4% (11/285) of patients. Median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). CRS resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥10%) included fever (84%), hypotension (29%) and aspartate aminotransferase increased (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4).

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Confirm that a minimum of 2 doses of tocilizumab are available prior to infusion of CARVYKTI.

Of the 285 patients who received CARVYKTI in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least 1 dose of corticosteroids for treatment of CRS.

Monitor patients at least daily for 7 days following CARVYKTI infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 2 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic toxicities, which may be severe, life-threatening, or fatal, occurred following treatment with CARVYKTI. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of Parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.

Among patients receiving CARVYKTI in the CARTITUDE-1 & 4 studies for RRMM, one or more neurologic toxicities occurred in 24% (69/285), including ≥ Grade 3 cases in 7% (19/285) of patients. Median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of the patients.

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI may experience fatal or life-threatening ICANS following treatment with CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS.

Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of the patients. Median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients, with a median time to resolution of 3 days (range: 1 to 143 days). Median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients, including those with ongoing neurologic events at the time of death or data cutoff. Of patients with ICANS, 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients, respectively.

Immune Effector Cell-associated Neurotoxicity Syndrome occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent (≥2%) manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep disorder (2%).

Monitor patients at least daily for 7 days following CARVYKTI infusion for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 2 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Advise patients to avoid driving for at least 2 weeks following infusion.

Parkinsonism: Neurologic toxicity with parkinsonism has been reported in clinical trials of CARVYKTI. Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥3 in 2% (5/285) of the patients. Median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days. Median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients, including those with ongoing neurologic events at the time of death or data cutoff. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients.

Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4).

Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease for the improvement or resolution of parkinsonism symptoms following CARVYKTI treatment.

Guillain-Barré syndrome: A fatal outcome following GBS occurred following treatment with CARVYKTI despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis.

Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS.

Immune mediated myelitis: Grade 3 myelitis occurred 25 days following treatment with CARVYKTI in CARTITUDE-4 in a patient who received CARVYKTI as subsequent therapy. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause.

Peripheral neuropathy occurred following treatment with CARVYKTI. Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of the patients. Median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range: 1 to 215 days). Median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data
cutoff.

Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and symptoms of peripheral neuropathies. Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS.

Cranial nerve palsies occurred following treatment with CARVYKTI. Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of the patients. Median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range: 1 to 209 days). Median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients, including those with ongoing neurologic events at the time of death or data cutoff. Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4).

The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected.

Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving CARVYKTI, with a median onset of 10 days (range: 8 to 99 days), and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia, and multi-organ dysfunction, including renal dysfunction and respiratory failure.

Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI.

HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards.

Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI infusion.

Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, Grade 3 or higher cytopenias not resolved by Day 30 following CARVYKTI infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285), and anemia 2% (6/285). After Day 60 following CARVYKTI infusion, 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death.

Monitor blood counts prior to and after CARVYKTI infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.

Infections: CARVYKTI should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after CARVYKTI infusion.

Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, infections occurred in 57% (163/285), including Grade ≥3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with CARVYKTI had an increased rate of fatal COVID-19 infections compared to the standard therapy arm.

Monitor patients for signs and symptoms of infection before and after CARVYKTI infusion and treat patients appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 5% of patients after CARVYKTI infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care, as medically indicated. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19.

Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.

Reactivation of John Cunningham (JC) virus, leading to progressive multifocal leukoencephalopathy (PML), including cases with fatal outcomes, have been reported following treatment. Perform appropriate diagnostic evaluations in patients with neurological adverse events.

Hypogammaglobulinemia can occur in patients receiving treatment with CARVYKTI. Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion occurred in 94% (267/285) of patients treated. Fifty-six percent (161/285) of patients received intravenous immunoglobulin (IVIG) post CARVYKTI for either an adverse reaction or prophylaxis.

Monitor immunoglobulin levels after treatment with CARVYKTI and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI treatment, and until immune recovery following treatment with CARVYKTI.

Hypersensitivity Reactions occurred following treatment with CARVYKTI. Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤2 Grade. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia.

Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction.

Immune effector cell-associated enterocolitis (IEC-EC) has occurred in patients treated with CARVYKTI. Manifestations include severe or prolonged diarrhea, abdominal pain, and weight loss requiring parenteral nutrition. IEC-EC has been associated with fatal outcome from perforation or sepsis. Manage according to institutional guidelines, including referral to gastroenterology and infectious disease specialists.

In cases of refractory IEC-EC, consider additional workup to exclude alternative etiologies, including T-cell lymphoma of the GI tract, which has been reported in the post marketing setting.

Secondary Malignancies: Patients treated with CARVYKTI may develop secondary malignancies. Among patients receiving CARVYKTI in the CARTITUDE-1 & -4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes.

Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples.

ADVERSE REACTIONS

The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia.

Please read full Prescribing Information, including Boxed Warning, for CARVYKTI.

(Press release, Johnson & Johnson, DEC 6, 2025, View Source [SID1234661221])

On December 6, 2025 Vivacta Bio, a spin-off company of Grit Biotherapeutics advancing in vivo CAR-T therapies for oncology and autoimmune diseases, reported encouraging initial data from an investigator-initiated, first-in-human study of GT801, a T-LNP/mRNA–based in vivo CAR-T candidate targeting CD19. The results were presented in an oral session by Dr. Pin Wang, Chief Scientific Officer of Grit Biotherapeutics, at the 2025 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, Florida. The presentation, titled "Precision In Vivo CAR-T Generation via CLAMP-Enabled mRNA Delivery: Toward Scalable and Translatable Cell Therapy," highlighted early clinical activity of GT801 and its potential to reshape CAR-T treatment delivery.

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The Phase 1 investigator-initiated study is evaluating the safety, tolerability, and preliminary efficacy of repeat GT801 dosing in patients with relapsed or refractory CD19-positive B-cell malignancies. As of the November 30, 2025 data cutoff, two patients with non-Hodgkin’s lymphoma had completed multiple GT801 administrations without lymphodepleting chemotherapy, demonstrating the feasibility of generating functional CAR-T cells in vivo in the absence of cytotoxic conditioning.

Patient 1 received three doses of 0.5 mg, and Patient 2 received four doses of 1.5 mg. GT801 was generally well tolerated. Both patients showed high CAR expression within circulating T cells. Durable and repeatable CAR-T expansion was observed following each GT801 administration. No CAR expression was detected in peripheral blood monocytes, suggesting negligible off‑target delivery of GT801 and supporting high selectivity of the T‑LNP platform.

GT801 induced rapid and profound pharmacodynamic activity, resulting in deep B-cell depletion in peripheral blood and across multiple tissues, with B cells effectively cleared in bone marrow and lymph node biopsies. By Week 4 following the final GT801 infusion, both patients achieved a partial response based on investigator assessment.

"We are encouraged by the promising safety profile and compelling efficacy signals observed with GT801 in heavily pretreated NHL patients," said Dr. Yarong Liu, Founder and CEO of Vivacta Bio. "These initial findings demonstrate GT801’s ability to generate potent, repeatable CAR-T responses without lymphodepleting chemotherapy – a major step forward for scalability, patient accessibility, and commercial viability."

About GT801

GT801 is an investigational, systemically administered in vivo CAR-T product candidate that uses T-cell–targeted lipid nanoparticles (T-LNPs) to deliver optimized mRNA encoding an anti-CD19 CAR. The platform integrates Grit Bio’s proprietary CLAMP (Controllable Ligand Attachment Modification and Purification) technology, enabling site-specific antibody conjugation, precise ligand density control, and selective T-cell targeting with minimal off-target uptake. GT801 is designed to generate potent and persistent CAR-T cells directly inside the patient, supporting repeat dosing and eliminating the need for conventional ex vivo cell manufacturing.

(Press release, Vivacta, DEC 6, 2025, View Source [SID1234661220])

On December 6, 2025 Kite, a Gilead Company (Nasdaq: GILD), and its partner Arcellx, reported new positive data from its pivotal iMMagine-1 Phase 2 study of anitocabtagene autoleucel (anito-cel), an investigational agent, which continues to show clinically meaningful deep and durable efficacy with predictable and manageable safety observed to date in relapsed or refractory multiple myeloma (RRMM) patients who had received at least three prior lines of therapy. These new findings from the ongoing study will be shared in an oral presentation (Abstract #256) today at 2:45 PM ET during the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"These data are compelling and are an important advancement for patients living with multiple myeloma," said Dr. Krina Patel, lead investigator, Associate Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "I am encouraged by the depth of responses in the iMMagine-1 study. For clinicians, we rely on therapies that deliver continued meaningful efficacy, a predictable safety profile, and reliable manufacturing. Anito-cel demonstrates that it could become a significant new treatment option in our efforts to improve outcomes for patients with multiple myeloma."

Data from an October 7, 2025 cutoff date, including 117 patients treated with anito-cel, who were followed for a median of 15.9 months, showed an independent review committee (IRC)-assessed overall response rate (ORR) of 96%, with 74% achieving a stringent complete response or complete response (sCR or CR) per International Myeloma Working Group (IMWG) criteria. 102 of 117 patients (87%) were triple refractory, 48 of 117 patients (41%) were penta refractory, 21 of 117 patients (18%) had extramedullary disease, and 47 of 117 patients (40%) had high risk cytogenetics. For many in this heavily pre-treated population, responses began quickly, often within one month. Median time to best response was 4.8 months and median time to sCR or CR was 3.2 months. Of the 96 patients evaluable for minimal residual disease (MRD) testing, 91 (95%) achieved MRD negativity at a median time of 1 month, meaning no cancer cells could be detected even with highly sensitive tests (≤10-5 sensitivity).

The progression-free survival (PFS) rates were 82.1% at 12 months, 67.4% at 18 months and 61.7% at 24 months, meaning many patients were still alive and free from cancer progression at those timepoints. The overall survival (OS) rates showed that a significant majority of patients remained alive, with 94% at 12 months, 88% at 18 months and 83% at 24 months. The median PFS and OS have not yet been reached, suggesting sustained and ongoing benefit for a majority of patients.

Importantly, no delayed (non-ICANS) neurotoxicities, including no Parkinsonism, no cranial nerve palsies, no Guillain-Barré syndrome, and no immune effector cell-associated enterocolitis, have been observed to date, with all patients dosed at least 12 months prior to the cutoff. In an exploratory study sponsored by Kite (Abstract #503), characterization of CD4+ CAR T cell subtypes provide further mechanistic hypotheses supporting the neurologic tolerability profile of anito-cel.

"For multiple myeloma patients in advanced treatment stages, effective options are critical as resistance to treatment grows," said Cindy Perettie, Executive Vice President, Kite. "The deep, durable responses seen with iMMagine-1, combined with a predictable and manageable safety profile and rapid and reliable manufacturing, highlight anito-cel’s potential to redefine care. Together with Arcellx, our goal is to deliver a differentiated, one-time treatment option in 2026 that may reduce patient burden and improve access, including in outpatient and community oncology settings."

Observed side effects were generally consistent with past readouts. Cytokine release syndrome (CRS) was observed in 86% of patients but was generally mild and manageable. In fact, 83% of patients in the study experienced no CRS or Grade 1 CRS (fever only). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 8% of patients, with only one Grade 3 case and all other cases Grade 2 or lower. The most common hematologic adverse events noted during treatment were low white blood cell counts (neutropenia) in 71% of patients, low red blood cells (anemia) in 28%, and low platelets (thrombocytopenia) in 26%. Grade 3 or higher infections occurred in 9% of patients.

Additional research presented at ASH (Free ASH Whitepaper) provided further insights into CAR T-cell therapies, detailing anito-cel’s mechanism and factors influencing treatment outcomes.

Preclinical research (Abstract #7644) shows that anito-cel’s D-Domain binder interacts with BCMA by binding and releasing quickly. Relative to a comparator CAR T-cell therapy in preclinical models, this transient interaction with cancer cells may be associated with decreased inflammation while maintaining the ability to effectively kill cancer cells. Additionally, the abstract shows anito-cel retains its ability to target cancer cells with altered BCMA expression after previous treatments, demonstrating the potential for anito-cel to maintain efficacy in patients previously exposed to BCMA-targeting therapies. Further research, including crystallography and epitope mapping, is ongoing to provide more detail on this mechanism.

About anitocabtagene autoleucel (anito-cel)

Anitocabtagene autoleucel (anito-cel, previously ddBCMA) is the first BCMA-directed CAR T-cell therapy to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact binder known as the D-Domain. The small, stable D-Domain binder enables high CAR expression without tonic signaling and is designed to quickly release from the BCMA target. This combination may allow for the effective elimination of multiple myeloma cells without severe immunotoxicity. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

About Multiple Myeloma

Multiple myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. MM is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple comorbidities and toxicities that can quickly escalate and become life-endangering.

About iMMagine-1

iMMagine-1 is a Phase 2 registrational, pivotal open-label study of anito-cel in patients with relapsed or refractory multiple myeloma (RRMM) who have received at least three prior regimens of systemic therapy including proteasome inhibitor, immunomodulatory drugs (IMiD) and anti-CD38 antibody and are refractory to the last line of therapy.

The trial assessed both safety and efficacy in 117 patients receiving a single infusion of anito-cel (target dose of 115×106 CAR+ viable T cells). Efficacy was assessed monthly for the first 6 months, then quarterly up to 2 years, or upon patient relapse. Long-term safety data will be collected under a separate long-term follow-up study for up to 15 years.

The primary endpoint is overall response rate (ORR) per International Myeloma Working Group (IMWG) criteria, as assessed by an independent review committee. Secondary endpoints include complete response rate (CR/sCR), progression-free survival, overall survival, duration of response, minimal residual disease negativity and safety.

(Press release, Gilead Sciences, DEC 6, 2025, View Source [SID1234661212])