Unprecedented results from the Phase 3 MajesTEC-3 study support TECVAYLI® plus DARZALEX FASPRO® as a potential standard of care as early as second line for patients with relapsed/refractory multiple myeloma

Rhea-AI Summary

Johnson & Johnson (NYSE:JNJ) reported Phase 3 MajesTEC-3 results showing TECVAYLI plus DARZALEX FASPRO significantly improved survival and response versus standard RRMM regimens at nearly three years follow-up.

Key outcomes: PFS HR 0.17 (83% risk reduction; P<0.0001), OS HR 0.46 (3-year OS 83.3% vs 65.0%), higher complete response (81.8% vs 32.1%), and higher MRD-negativity (58.4% vs 17.1%).

Safety: similar Grade 3/4 TEAE rates; higher infection rates but reduced after six months with prophylaxis.

Regulatory: sBLA submitted; U.S. FDA granted Breakthrough Therapy Designation and review via RTOR.

Positive

• Progression-free survival HR 0.17 (83% risk reduction)
• Overall survival HR 0.46
• 3-year OS rates 83.3% vs 65.0%
• Complete response rate 81.8% vs 32.1%
• MRD-negativity 58.4% vs 17.1%
• FDA Breakthrough Therapy Designation and sBLA under RTOR

Negative

• Any-grade infections higher: 96.5% vs 84.1%
• Grade 3/4 infections higher: 54.1% vs 43.4%
• Serious adverse events: 70.7% vs 62.4%
• Grade 5 TEAEs: 7.1% vs 5.9%
• Cytokine release syndrome occurred in 60.1% (all Grade 1/2)

Key Figures

PFS/OS risk reduction 83% reduction (HR 0.17; 95% CI 0.12–0.23; P<0.0001) Risk of progression or death vs standard regimens at ~3-year follow-up

Durable PFS 91% Patients progression-free at 6 months who remained progression-free at 3 years

Complete response rate 81.8% vs 32.1% (OR 9.56; 95% CI 6.47–14.14) ≥CR at 3-year follow-up, TECVAYLI + DARZALEX FASPRO vs DPd/DVd

MRD-negativity 58.4% vs 17.1% (OR 6.78; 95% CI 4.53–10.15; P<0.0001) MRD-negative rates at 3 years with high evaluable rates

Overall survival rates 83.3% vs 65.0% 3-year OS for TECVAYLI + DARZALEX FASPRO vs standard of care

Infection rates Any grade 96.5% vs 84.1%; Grade 3/4 54.1% vs 43.4% Infections with TECVAYLI + DARZALEX FASPRO vs DPd/DVd control

Cytokine release syndrome 60.1% (all Grade 1/2) CRS incidence; no discontinuations and managed per guidelines

ICANS incidence 1.1% Immune effector cell-associated neurotoxicity syndrome in TECVAYLI + DARZALEX FASPRO arm

Market Reality Check

$201.62 Last Close

Volume Volume 7,589,450 vs 20-day average 9,526,578, indicating quieter-than-normal trading pre-release. normal

Technical Price $201.62 is above the $170.47 200-day MA and within 3% of the $207.81 52-week high.

Peers on Argus

JNJ was down 0.15% while key pharma peers were mixed (e.g., AZN +1.01%, LLY -1.3%, NVS -2%), suggesting this news was more stock-specific than a broad sector move.

Common Catalyst Multiple large-cap drug makers reported oncology trial updates, but price moves were not uniformly directional across peers.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 03	Awareness partnership	Positive	-0.0%	Eye-health self-care campaign with Naomi Watts targeting people over 40.
Nov 18	Regulatory approval	Positive	+0.2%	TREMFYA SC induction regimen approval for ulcerative colitis with strong Phase 3 data.
Nov 17	Clinical data update	Positive	+1.9%	TREMFYA Phase 3b APEX data showing sustained inhibition of joint damage in PsA.
Nov 17	Oncology acquisition	Positive	+1.9%	$3.05B Halda Therapeutics acquisition adding RIPTAC platform and HLD-0915 asset.
Nov 06	FDA oncology approval	Positive	-0.2%	DARZALEX FASPRO approval for high-risk smoldering multiple myeloma with 51% risk reduction.

Pattern Detected

Recent R&D and regulatory news for JNJ more often aligned with modest positive price reactions, though there are occasional small divergences on approvals and campaigns.

Recent Company History

Over the past few months, Johnson & Johnson has reported several positive milestones, including an FDA approval for DARZALEX FASPRO in high-risk smoldering multiple myeloma on Nov 6, 2025 and strong Phase 3 data for TREMFYA in psoriatic arthritis. It also announced a $3.05 billion oncology acquisition and additional TREMFYA ulcerative colitis data. A prior MajesTEC-3 topline release on Oct 16, 2025 already highlighted PFS and OS benefits, making today’s detailed Phase 3 results a continuation of this oncology-focused trajectory.

Market Pulse Summary

This announcement details mature Phase 3 MajesTEC-3 results, with TECVAYLI plus DARZALEX FASPRO achieving an 83% risk reduction in progression or death and strong complete response and MRD-negative rates at nearly three years. Overall survival favored the combination, and safety events such as cytokine release syndrome were mostly low grade and manageable, though infections were frequent. The news builds on prior topline results and an sBLA filing, reinforcing JNJ’s multiple myeloma franchise while highlighting the need to monitor regulatory outcomes and long-term safety.

Key Terms

progression-free survival medical

"combination led to a statistically significant progression-free survival and overall survival advantage"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

overall survival medical

"combination led to a statistically significant progression-free survival and overall survival advantage"

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

hazard ratio medical

"risk of disease progression or death compared to standard regimens at nearly three-years follow-up (hazard ratio [HR], 0.17;"

A hazard ratio is a way scientists compare the chance of something happening over time between two groups, like patients taking different medicines. If the ratio is high, it means one group is more likely to experience the event sooner or more often, which helps determine how effective a treatment is or how risky a situation might be.

minimal residual disease medical

"including treatment response rates, minimal residual disease (MRD)-negativity, overall survival (OS), and time"

Minimal residual disease (MRD) is the tiny number of cancer cells that remain in the body after treatment, often too few to show up on standard scans but detectable with very sensitive tests. For investors, MRD is important because it predicts the risk of relapse and can determine whether a therapy is seen as effective, influences regulatory and reimbursement decisions, and affects the size and timing of a drug’s market opportunity—like spotting the last weeds that can make a garden regrow if not removed.

cytokine release syndrome medical

"Cytokine release syndrome occurred in 60.1% of patients; all cases were Grade 1/2,"

An intense immune overreaction in which the body's defense system releases a large surge of signaling proteins, causing fever, low blood pressure, breathing trouble or organ stress; imagine the immune system's alarm going into overdrive and flooding the body with emergency responders. Investors care because this side effect can slow or block regulatory approval, increase clinical trial costs and liabilities, limit how widely a therapy can be used, and therefore affect a drug's market value and sales potential.

immune effector cell-associated neurotoxicity syndrome medical

"Immune effector cell-associated neurotoxicity syndrome was rare and occurred in 1.1% of patients."

immune effector cell-associated neurotoxicity syndrome (ICANS) is a brain-related side effect that can occur after treatments that activate powerful immune cells, such as engineered cell therapies. It can cause confusion, speech problems, seizures or coma when the immune response unintentionally harms brain function; think of an overenthusiastic security system that starts damaging the house it’s protecting. Investors care because ICANS affects clinical trial results, regulatory approvals, product labeling, treatment adoption, monitoring costs and potential liability, all of which influence a therapy’s commercial value.

Biologics License Application regulatory

"submitted a supplemental Biologics License Application (sBLA) for the use of TECVAYLI"

A biologics license application is a formal request submitted to regulatory authorities seeking approval to market a new biological medicine, such as vaccines or treatments made from living organisms. It is a comprehensive review process that evaluates the safety, effectiveness, and manufacturing quality of the product. For investors, receiving approval signals that a biological therapy can be sold to the public, potentially leading to revenue growth and market success.

AI-generated analysis. Not financial advice.

TECVAYLI^® and DARZALEX FASPRO^® combination led to a statistically significant progression-free survival and overall survival advantage compared to standard treatment after three years of follow-up

Combination regimen granted Breakthrough Therapy Designation by U.S. FDA

ORLANDO, Fla., Dec. 9, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ), the worldwide leader in multiple myeloma, today announced new data from the investigational Phase 3 MajesTEC-3 study that demonstrate the potential of TECVAYLI^® (teclistamab-cqyv) plus DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) as early as second line for patients with relapsed/refractory multiple myeloma (RRMM). Results show an 83% reduction in the risk of disease progression or death compared to standard regimens at nearly three-years follow-up (hazard ratio [HR], 0.17; 95 percent confidence interval [CI], 0.12-0.23; P<0.0001).¹ Ninety-one percent of patients who were progression-free at six months remained progression-free at three years.²

The study evaluated the efficacy and safety of the investigational immunotherapy combination of TECVAYLI^® plus DARZALEX FASPRO^® versus DARZALEX FASPRO^® and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients with RRMM who have received 1-3 prior lines of therapy. The data were presented as a late-breaking oral presentation and in the press program at the 2025 American Society of Hematology (ASH) Annual Meeting, with simultaneous publication in The New England Journal of Medicine.

"The combination of TECVAYLI and DARZALEX FASPRO offers remarkable efficacy, a well-characterized safety profile with robust infection management protocols, and an opportunity to improve patient outcomes across academic and community settings. It has the potential to change the standard of care as a steroid-sparing combination regimen suited for outpatient administration on the familiar DARZALEX schedule," said Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Hematology, University Hospital of Salamanca.* "TECVAYLI and DARZALEX FASPRO work synergistically by uniquely targeting both BCMA and CD38 to prime and activate the immune system. The combination has shown to extend progression-free survival and overall survival versus standard of care as early as second line."

Significant improvements compared to standard of care were observed across key secondary endpoints, including treatment response rates, minimal residual disease (MRD)-negativity, overall survival (OS), and time to worsening of symptoms – revealing the comprehensive impact of the combination across varied patient measures.¹ TECVAYLI^® plus DARZALEX FASPRO^® showed higher rates of complete response (≥CR) (81.8% vs. 32.1%; odds ratio [OR], 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs. 75.3%; OR, 2.65; 95% CI, 1.68-4.18) and MRD-negativity (58.4% vs. 17.1%; OR, 6.78; 95% CI, 4.53-10.15, P<0.0001; evaluable rate of 89.3% vs. 63.0%) at three-years follow-up.¹ OS favored TECVAYLI^® plus DARZALEX FASPRO^® (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001) across all prespecified subgroups. At three-years, OS rates were 83.3% and 65.0%, respectively.¹ Additionally, patients remained symptom-free significantly longer with TECVAYLI^® plus DARZALEX FASPRO^® versus standard of care, underscoring a significant improvement in patient-reported quality of life (QoL) outcomes.¹

"With these data, we are entering a new era in treating multiple myeloma with the first bispecific combination to demonstrate superior overall survival as early as second line. Alongside the other transformational therapies in our leading portfolio, we can offer patients optimal outcomes at any stage of disease – bringing us closer to our ultimate ambition to find a cure," said Sen Zhuang, M.D., Vice President, Oncology Clinical Research, Johnson & Johnson Innovative Medicine. "With TECVAYLI plus DARZALEX FASPRO we have the potential to set a new standard of care once again for this disease. We continue to explore how regimens with our bispecifics portfolio can redefine the future for patients."

In the study, TECVAYLI^® plus DARZALEX FASPRO^® and standard of care comparators had similar rates of Grade 3/4 (95.1% vs. 96.6%) treatment-emergent adverse events (TEAE).¹ Most Grade 3/4 events were due to cytopenia and infection.¹ Infections were observed with TECVAYLI^® and DARZALEX FASPRO^® (any grade, 96.5%; Grade 3/4, 54.1%) and DPd/DVd control (any grade 84.1%; Grade 3/4 43.4%). Grade 3 or higher infections with TECVAYLI^® and DARZALEX FASPRO^® declined after the first 6 months of treatment with use of established immunoglobulin supplementation and infection prophylaxis protocols, along with switch to monthly dosing.¹ Cytokine release syndrome occurred in 60.1% of patients; all cases were Grade 1/2, did not lead to treatment discontinuation and were effectively managed using standard guidelines.¹ Immune effector cell-associated neurotoxicity syndrome was rare and occurred in 1.1% of patients.¹ Serious adverse events occurred in 70.7% of patients compared to 62.4% of patients treated with the control regimen, while treatment discontinuations due to adverse events were low (4.6% vs. 5.5%).¹ Grade 5 TEAEs were 7.1% and 5.9% with TECVAYLI^® plus DARZALEX FASPRO^® and DPd/DVd control, respectively.¹ 

Based on these results, Johnson & Johnson is working with regulatory bodies globally to bring the benefits of this bispecific regimen to eligible patients as quickly as possible. The Company has submitted a supplemental Biologics License Application (sBLA) for the use of TECVAYLI^® and DARZALEX FASPRO^® in combination as a treatment for RRMM to the U.S. Food and Drug Administration (FDA). The FDA has granted Breakthrough Therapy Designation (BTD) for the combination regimen; BTD is granted to expedite the development and regulatory review of a medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement over available therapies on a clinically significant endpoint(s).

The sBLA is being reviewed through the Real-Time Oncology Review (RTOR) program, which enables the agency to initiate their evaluation of the data before the full application is formally submitted. An application has also been submitted to Brazil's health agency, ANVISA (Agência Nacional de Vigilância Sanitária).

About the MajesTEC-3 Study
MajesTEC-3 (NCT05083169) is an ongoing, Phase 3 randomized study evaluating the safety and efficacy of teclistamab plus daratumumab versus investigator's choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients with relapsed/refractory multiple myeloma who have received 1–3 prior lines of therapy. The primary endpoint is progression-free survival (PFS) and secondary endpoints include complete response or better (≥CR), overall response rate, minimal residual disease (MRD)-negativity (10⁻⁵ by next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety. The MajesTEC-3 study is a part of the MajesTEC clinical program, which includes exploring the potential of teclistamab as a combination regimen.³

About TECVAYLI^®
TECVAYLI^® (teclistamab-cqyv) is a first-in-class, bispecific T-cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. TECVAYLI^® received accelerated approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.⁴

In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI^® for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months. Since FDA approval, more than 20,800 patients have been treated worldwide with TECVAYLI^®.
 
The European Commission (EC) granted TECVAYLI^® conditional marketing authorization in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI^®, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients who have achieved a complete response or better for a minimum of six months.

For more information, visit www.TECVAYLI.com.

About DARZALEX FASPRO^® and DARZALEX^®
DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for 11 indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.⁵ It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO^® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE^® drug delivery technology.

DARZALEX^® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.⁶ In 2025, DARZALEX FASPRO^® was approved by the U.S. FDA and EMA as the first and only treatment for patients with high-risk smoldering multiple myeloma.

DARZALEX^® is the first CD38-directed antibody approved to treat multiple myeloma.⁵ DARZALEX^®-based regimens have been used in the treatment of more than 618,000 patients worldwide and more than 68,000 patients in the U.S. alone.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

For more information, visit www.DARZALEX.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.⁷ In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.^8. Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.⁹ 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.¹⁰ People living with multiple myeloma have a 5-year survival rate of 59.8 percent.¹¹ 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.^12,13

TECVAYLI^® IMPORTANT SAFETY INFORMATION

INDICATION AND USAGE

TECVAYLI^® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI^®. Initiate treatment with TECVAYLI^® step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI^® until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI^®. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI^® until neurologic toxicity resolves or permanently discontinue based on severity.

TECVAYLI^® is available only through a restricted program called the TECVAYLI^® and TALVEY^® Risk Evaluation and Mitigation Strategy (REMS).

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome - TECVAYLI^® can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI^® at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI^®. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).

Initiate therapy according to TECVAYLI^® step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI^® accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI^® based on severity.

TECVAYLI^® is available only through a restricted program under a REMS.

Neurologic Toxicity including ICANS - TECVAYLI^® can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI^® at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI^®.

In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI^® at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI^®. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI^® based on severity per recommendations and consider further management per current practice guidelines.

Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI^® step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

TECVAYLI^® is available only through a restricted program under a REMS.

TECVAYLI^® and TALVEY^® REMS - TECVAYLI^® is available only through a restricted program under a REMS called the TECVAYLI^® and TALVEY^® REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Hepatotoxicity - TECVAYLI^® can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Infections - TECVAYLI^® can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%.

Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI^® and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Monitor immunoglobulin levels during treatment with TECVAYLI^® and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Neutropenia - TECVAYLI^® can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI^® at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.

Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI^® based on severity.

Hypersensitivity and Other Administration Reactions - TECVAYLI^® can cause both systemic administration-related and local injection-site reactions. Systemic Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions - In patients who received TECVAYLI^® at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI^® or consider permanent discontinuation of TECVAYLI^® based on severity.

Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI^® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI^® and for 5 months after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI^®.

DARZALEX^® INDICATIONS AND IMPORTANT SAFETY INFORMATION

INDICATIONS
DARZALEX^® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

• In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
• In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
• In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
• In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
• In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
• As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

DARZALEX^® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

DARZALEX^® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX^®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.

When DARZALEX^® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX^®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX^® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX^® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX^® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX^® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX^® infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX^®. Type and screen patients prior to starting DARZALEX^®.

Neutropenia and Thrombocytopenia

DARZALEX^® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX^® until recovery of neutrophils or for recovery of platelets.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX^® can cause fetal harm when administered to a pregnant woman. DARZALEX^® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX^® and for 3 months after the last dose.

The combination of DARZALEX^® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS

The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX^® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.

Please click here to see the full Prescribing Information.

About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com.

Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC and Janssen Scientific Affairs, LLC are Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of TECVAYLI^® (teclistamab-cqyv) and DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments.

Footnotes
*Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Hematology, University Hospital of Salamanca, has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work.

¹ Maria-Victoria Mateos, et. al., Phase 3 Randomized Study of Teclistamab Plus Daratumumab Versus Investigator's Choice of Daratumumab and Dexamethasone With Either Pomalidomide or Bortezomib (DPd/DVd) in Patients With Relapsed Refractory Multiple Myeloma (RRMM): Results of MajesTEC-3, 2025 American Society of Hematology Annual Meeting. Accessed December 2025.
² Mateos, M.V., Moreau, P., Garfall, A. L., van de Donk, N. W. C. J., et al. (2025) Teclistamab plus daratumumab versus standard regimens in relapsed or refractory multiple myeloma: MajesTEC-3 Trial Results. The New England Journal of Medicine, 393(23), https://doi.org/10.1056/NEJMoa2514663.
³ MajesTEC-3, NCT05083169. A Phase 3 Randomized Study Comparing Teclistamab + Subcutaneous Daratumumab (Tec-Dara) Versus Daratumumab SC + Pomalidomide + Dexamethasone (DPd) or Daratumumab SC + Bortezomib + Dexamethasone (DVd). https://clinicaltrials.gov/study/NCT05083169. Accessed December 2025.
⁴ U.S. FDA Approves TECVAYLI^® (teclistamab-cqyv), the First Bispecific T-cell Engager Antibody for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. https://www.jnj.com/u-s-fda-approves-tecvayli-teclistamab-cqyv-the-first-bispecific-t-cell-engager-antibody-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma. Accessed December 2025.
⁵ DARZALEX FASPRO^® U.S. Prescribing Information.
⁶ DARZALEX^® U.S. Prescribing Information.
⁷ Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178.
⁸ National Cancer Institute. Plasma cell neoplasms. National Institutes of Health. https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq. Accessed October 2025.
⁹ City of Hope. Multiple myeloma: Causes, symptoms & treatments. https://www.cancercenter.com/cancer-types/multiple-myeloma. Accessed December 2025.
¹⁰ American Cancer Society. Myeloma cancer statistics. https://cancerstatisticscenter.cancer.org/types/myeloma. Accessed December 2025.
¹¹ SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/explorer/. Accessed December 2025.
¹²American Cancer Society. What is multiple myeloma? https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed December 2025.
¹³ American Cancer Society. Multiple myeloma early detection, diagnosis, and staging. https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html. Accessed December 2025.  

 

Media contact: Oncology Media Relations oncology_media_relations@its.jnj.com

Investor contact: Lauren Johnson  investor-relations@its.jnj.com    U.S. Medical Inquiries  +1 800 526-7736

 

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SOURCE Johnson & Johnson

FAQ

What did the MajesTEC-3 trial report for JNJ on December 9, 2025?

MajesTEC-3 showed TECVAYLI plus DARZALEX FASPRO improved PFS (HR 0.17) and OS (HR 0.46) at nearly three years.

How much did TECVAYLI plus DARZALEX FASPRO reduce progression risk vs standard care in MajesTEC-3?

Progression risk was reduced by 83% versus standard regimens (PFS HR 0.17).

What were the 3-year overall survival rates reported for JNJ (JNJ) MajesTEC-3?

Three-year OS rates were 83.3% with the combination versus 65.0% with control.

What response and MRD results did MajesTEC-3 report for JNJ (JNJ)?

Complete response was 81.8% vs 32.1%; MRD-negativity was 58.4% vs 17.1% at three years.

What are the main safety concerns from the MajesTEC-3 data for JNJ (JNJ)?

Infections were higher with the combination (any grade 96.5%; Grade 3/4 54.1%) and serious AEs were 70.7%.

What regulatory steps has JNJ taken after the MajesTEC-3 results on December 9, 2025?

Johnson & Johnson submitted an sBLA, received FDA Breakthrough Therapy Designation, and is under RTOR review.