American Society of Hematology (ASH) Annual Meeting and Exposition | ASH 2025 | Orlando, Florida | iPharmaCenter
- Badari Andukuri
- 48 minutes ago
- 7 min read
KITE, GILEAD COMPANY
Kite and Arcellx Present Strong Pivotal iMMagine-1 Data at ASH 2025, Showing Durable and Deep Responses with Anito-cel in Heavily Pretreated Multiple Myeloma
Kite unveiled promising new results from the pivotal iMMagine-1 Phase 2 trial of anitocabtagene autoleucel (anito-cel), their investigational BCMA-directed CAR T-cell therapy for relapsed or refractory multiple myeloma (RRMM).
Also read: HAS Issues Conditional Reimbursement for JAYPIRCA (Pirtobrutinib) in Relapsed or Refractory Mantle Cell Lymphoma
Efficacy of Anitocabtagene Autoleucel (Anito-cel)
At the October 7, 2025, data cutoff, 117 participants had received anito-cel and were followed for a median of 15.9 months. Based on an independent review committee (IRC) assessment, the therapy produced an overall response rate (ORR) of 96%, with 74% achieving stringent complete or complete response (sCR/CR) according to International Myeloma Working Group (IMWG) criteria. Among the treated population, 87% were triple-refractory, 41% penta-refractory, and 40% carried high-risk cytogenetic features, signaling strong activity even among difficult-to-treat patients.
Responses appeared early, often within the first month, with a median time to best response of 4.8 months and median time to sCR/CR of 3.2 months. Furthermore, 95% of evaluable patients achieved minimal residual disease (MRD) negativity within one month of treatment, indicating deep molecular remission.
Durability of response continues to strengthen. Estimated progression-free survival (PFS) rates reached 82.1% at 12 months, 67.4% at 18 months, and 61.7% at 24 months, while overall survival (OS) remained high at 94%, 88%, and 83%, respectively, over the same periods. Median PFS and OS have not yet been reached, suggesting ongoing clinical benefit across the cohort.
The safety profile was consistent with earlier results and generally manageable. Cytokine release syndrome (CRS) occurred in 86% of patients, but the majority of cases were low grade; 83% experienced either no CRS or Grade 1 CRS (typically limited to fever). Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 8% of patients, with one Grade 3 event and the rest Grade 2 or below. Notably, there were no reports of delayed neurotoxicity or immune effector cell-associated enterocolitis across both Phase 1 and Phase 2 trials.
About Anitocabtagene Autoleucel (Anito-cel): Mechanism of action and designations
Anito-cel-formerly ddBCMA is the first BCMA-targeted CAR T-cell therapy in multiple myeloma to employ Arcellx’s proprietary D-Domain binder technology. The compact D-Domain allows high CAR expression and rapid release from the BCMA target, potentially enabling potent tumor cell elimination with reduced immune-related toxicities.
The candidate has received Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy (RMAT) designations from the U.S. Food and Drug Administration. Based on these positive iMMagine-1 outcomes, Kite and Arcellx expect to move toward a planned U.S. launch in 2026.
Kite Unveils Promising Phase 1 Results for Bicistronic CAR T-Cell Therapies in B-Cell Lymphoma
Kite has released early-phase clinical data showing that its next-generation bicistronic CAR T-cell therapies, KITE-753 and KITE-363, may offer meaningful activity with a manageable safety profile in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL).
KITE-753 and KITE-363 are autologous bicistronic CAR T-cell products designed to recognize two B‑cell antigens, CD19 and CD20, and to incorporate dual co-stimulation with CD28 and 4‑1BB to enhance T‑cell activation and persistence. These therapies are being evaluated in a Phase 1 setting in patients with heavily pretreated R/R LBCL, where there remains a need for more effective and tolerable options.
Mechanism and KITE DuoCore design
Both candidates use Kite’s DuoCore construct, which encodes two independent CARs that act together to address tumor antigen escape and heterogeneity. Targeting CD19 and CD20 simultaneously, along with dual co-stimulation, is intended to deepen responses, prolong CAR T-cell function, and potentially allow safer outpatient or community-based administration by reducing severe toxicity risk.
KITE-753 Phase 1 efficacy signals
In the Phase 1 trial of KITE-753, early results indicate high rates of deep responses among CAR T–naïve patients treated at the third dose level (DL3, 0.2×10⁶ CAR T cells/kg). At a median follow-up of about four months overall and just under three months at DL3, 11 of 14 CAR‑naïve patients (79%) at this dose achieved a complete response, and across all dose levels 14 of 20 CAR‑naïve patients achieved complete response, despite all having measurable, active disease at infusion and only limited corticosteroid and/or radiation as bridging therapy, which itself did not induce responses at DL3.
About KITE-753 and KITE-363
KITE-753 and KITE-363 remain investigational and are being positioned to address challenges such as antigen loss and relapse after single-antigen CAR T therapy. While KITE‑753 focuses on lymphoma with an enhanced manufacturing approach, KITE‑363 is also being explored in difficult-to-treat autoimmune diseases, reflecting broader ambitions for DuoCore-based CAR T-cell platforms.
TAKEDA
Protagonist and Takeda: Rusfertide Shows Durable Hematocrit Control in Polycythemia Vera at ASH 2025
Protagonist Therapeutics and Takeda presented 52-week data from the Phase 3 VERIFY trial of rusfertide, demonstrating sustained hematocrit control and reduced need for phlebotomy in patients with polycythemia vera (PV) who remained symptomatic despite standard care.
Among patients continuously treated with rusfertide, 61.9% achieved durable response without phlebotomy eligibility from baseline through week 52, building on the positive 32-week primary analysis that met all key endpoints. Crossover patients switching from placebo to rusfertide at week 32 also showed strong responses, with 77.9% free from phlebotomy eligibility between weeks 40-52.
Mean hematocrit stayed below 43% through week 52 in rusfertide-treated patients, compared to placebo where median time to hematocrit ≥45% was 8.3 weeks.
Median time to first phlebotomy reached 16 weeks in placebo versus not reached in rusfertide arms.
Quality-of-life measures, including PROMIS Fatigue and MFSAF scores, showed maintained improvements.
Longer-term data from the REVIVE/THRIVE studies indicated a 13-fold drop in annual phlebotomy rates from baseline after four years.
PFIZER
HYMPAVZI (Marstacimab) Slashes Bleeds by 93% vs On-Demand Therapy in Hemophilia A/B with Inhibitors in Phase 3 BASIS Trial
Pfizer reported detailed Phase 3 BASIS data for HYMPAVZI (marstacimab) in adults and adolescents with severe hemophilia A or B with inhibitors, showing clear superiority over on-demand (OD) treatment with bypassing agents. During the 6‑month observational phase, patients received OD intravenous bypassing agents as part of usual care, then transitioned to a 12‑month active treatment phase with HYMPAVZI. In this phase, 48 participants were treated with a 300 mg subcutaneous loading dose, followed by once-weekly 150 mg maintenance dosing. HYMPAVZI was delivered via a simple, once-weekly subcutaneous injection with minimal preparation and did not require routine treatment-related laboratory monitoring.
The study demonstrated a statistically significant and clinically meaningful 93% reduction in mean treated annualized bleeding rate (ABR) with HYMPAVZI compared with OD bypassing agents, with mean treated ABR of 1.39 versus 19.78, respectively. This benefit was consistent across hemophilia type (A or B), age groups, and geographic regions.
Additionally, the median ABR with HYMPAVZI was 0 compared with 16.42 on OD treatment, reinforcing the magnitude of bleed reduction. Superiority (p<0.0001) was also observed across all bleeding-related secondary endpoints, including spontaneous bleeds, joint bleeds, target joint bleeds, and total treated and untreated bleeds. HYMPAVZI was generally well tolerated, with no unexpected safety signals.
HYMPAVZI also showed favorable effects on health-related quality of life after six months in the active treatment phase. Patients receiving HYMPAVZI experienced a marked improvement in the Haem-A-QoL physical health domain, reflecting reduced physical burden such as joint pain, swelling, and mobility difficulties. Total Haem-A-QoL scores also improved, indicating better overall quality of life across multiple daily activity and psychological domains. Gains were seen in EQ-5D-5L index scores, capturing aspects like mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, suggesting broader functional and emotional benefits. The EQ-VAS, representing patients’ own overall health rating, also numerically improved, further supporting the positive impact of prophylactic HYMPAVZI on day-to-day living compared with episodic OD therapy.
JOHNSON AND JOHNSON
Earlier-Line CARVYKTI Delivers Durable 2.5-Year Treatment-Free Remissions in Relapsed/Refractory Multiple Myeloma in CARTITUDE-4
Johnson & Johnson presented updated CARTITUDE-4 results showing that earlier use of CARVYKTI (ciltacabtagene autoleucel) can deliver durable, treatment-free remissions in relapsed or refractory multiple myeloma. In this Phase 3 study, 176 patients received CARVYKTI as early as second line, and a subset of 59 patients had standard-risk cytogenetics.
At a median follow-up of 33.6 months, the 30‑month progression-free survival (PFS) rate in the standard-risk, as-treated group appeared to plateau at about 80.5% after a single infusion. This indicates that the majority of these patients remained alive without disease progression and without needing additional myeloma therapy 2.5 years after treatment. Notably, all 26 patients in this subset who achieved minimal residual disease (MRD)–negative complete response at 12 months remained progression-free at 30 months, underscoring the depth and durability of response associated with MRD negativity.
These findings add to a growing body of clinical and real-world evidence for CARVYKTI, which has now been used in more than 9,000 patients globally. CARTITUDE-4 is the first randomized Phase 3 trial evaluating CARVYKTI against standard-of-care regimens PVd (pomalidomide, bortezomib, dexamethasone) or DPd (daratumumab, pomalidomide, dexamethasone) in adults with relapsed, lenalidomide-refractory multiple myeloma after one to three prior lines of therapy. The primary endpoint is PFS, with secondary endpoints including overall survival, MRD-negative rate, and overall response rate. The durable PFS signal and plateau in standard-risk patients treated early suggest a potential “functional cure fraction” in this population and support integration of CAR T therapy earlier in the treatment algorithm.
CARTITUDE-1 provides complementary data in a later-line setting. This Phase 1b/2, open-label, multicenter study evaluated cilta-cel in adults with heavily pretreated RRMM, the vast majority of whom were refractory to their last line of therapy and triple-class refractory to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. The Phase 1b portion, which enrolled 29 patients, focused on characterizing safety and confirming the dose based on experience from the first-in-human LEGEND-2 study of LCAR-B38M.
The safety profile from CARTITUDE-1 supported evaluation of outpatient dosing in subsequent CARTITUDE studies. The Phase 2 portion assessed efficacy with overall response rate as the primary endpoint in a population historically expected to have a median PFS under six months and median overall survival around one year. The robust responses and survival outcomes seen in CARTITUDE-1 underpin the rationale for moving cilta-cel earlier in the disease course, as reflected in the CARTITUDE-4 results.