Johnson & Johnson files for U.S. FDA approval of DARZALEX FASPRO®-based quadruplet regimen for newly diagnosed multiple myeloma patients for whom transplant is not planned
Johnson & Johnson (NYSE:JNJ) has submitted a supplemental Biologics License Application (sBLA) to the FDA for a new indication of DARZALEX FASPRO® in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for newly diagnosed multiple myeloma patients ineligible for or deferring autologous stem cell transplant. The submission is based on the Phase 3 CEPHEUS study, which showed:
- 60.9% of patients achieved minimal residual disease (MRD)-negativity with D-VRd
- 43% reduction in risk of progression or death
- Overall MRD-negativity rate of 60.9% vs 39.4% for VRd alone
- Sustained MRD-negativity rate of 48.7% vs 26.3% for VRd
- Complete response rate of 81.2% vs 61.6% for VRd
The safety profile was consistent with known profiles for DARZALEX FASPRO® and VRd. This could potentially be the first FDA-approved treatment regimen for newly diagnosed multiple myeloma based on MRD-negativity as the primary endpoint.
Johnson & Johnson (NYSE:JNJ) ha presentato una domanda di licenza biologica supplementare (sBLA) alla FDA per una nuova indicazione di DARZALEX FASPRO® in combinazione con bortezomib, lenalidomide e dexametasone (D-VRd) per pazienti con mieloma multiplo recentemente diagnosticati non idonei o che rinviano il trapianto autologo di cellule staminali. La presentazione si basa sullo studio di Fase 3 CEPHEUS, che ha mostrato:
- Il 60.9% dei pazienti ha raggiunto la negatività della malattia residua minimale (MRD) con D-VRd
- Riduzione del 43% del rischio di progressione o morte
- Il tasso complessivo di negatività per MRD è stato del 60.9% rispetto al 39.4% per VRd da solo
- Tasso sostenuto di negatività per MRD del 48.7% rispetto al 26.3% per VRd
- Tasso di risposta completa dell'81.2% rispetto al 61.6% per VRd
Il profilo di sicurezza è stato coerente con i profili noti per DARZALEX FASPRO® e VRd. Questo potrebbe potenzialmente essere il primo regime di trattamento approvato dalla FDA per il mieloma multiplo recentemente diagnosticato basato sulla negatività della MRD come obiettivo primario.
Johnson & Johnson (NYSE:JNJ) ha presentado una solicitud de licencia biológica suplementaria (sBLA) a la FDA para una nueva indicación de DARZALEX FASPRO® en combinación con bortezomib, lenalidomida y dexametasona (D-VRd) para pacientes con mieloma múltiple recién diagnosticados que no son elegibles o que posponen el trasplante autólogo de células madre. La presentación se basa en el estudio de fase 3 CEPHEUS, que mostró:
- El 60.9% de los pacientes logró negatividad para enfermedad residual mínima (MRD) con D-VRd
- Reducción del 43% en el riesgo de progresión o muerte
- Tasa general de negatividad de MRD del 60.9% frente al 39.4% para VRd solo
- Tasa sostenida de negatividad de MRD del 48.7% frente al 26.3% para VRd
- Tasa de respuesta completa del 81.2% frente al 61.6% para VRd
El perfil de seguridad fue coherente con los perfiles conocidos de DARZALEX FASPRO® y VRd. Esto podría ser potencialmente el primer régimen de tratamiento aprobado por la FDA para el mieloma múltiple recién diagnosticado basado en la negatividad de MRD como objetivo primario.
존슨앤드존슨 (NYSE:JNJ)이 새로운 적응증에 대한 보충 생물학적 라이센스 신청서(sBLA)를 FDA에 제출했습니다: DARZALEX FASPRO®와 보르테조밉, 레날리도마이드, 덱사메타손(D-VRd)의 병용요법으로, 자가 조혈모세포 이식을 받을 수 없는 또는 연기하는 새로 진단된 다발성 골수종 환자들을 위한 것입니다. 제출은 3상 CEPHEUS 연구를 기반으로 하며, 해당 연구에서 다음과 같은 결과가 나타났습니다:
- 60.9%의 환자가 D-VRd로 최소 잔여 질병(MRD) 음성을 달성했습니다.
- 진행 또는 사망 위험이 43% 감소했습니다.
- 전체 MRD 음성 비율은 60.9%로 VRd 단독의 39.4%에 비해 높았습니다.
- 지속적인 MRD 음성 비율은 48.7%로 VRd의 26.3%에 비해 높았습니다.
- 완전 반응 비율은 81.2%로 VRd의 61.6%에 비해 높았습니다.
안전성 프로필은 DARZALEX FASPRO® 및 VRd에 대한 알려진 프로필과 일치했습니다. 이는 MRD 음성을 주요 목표로 하는 새로 진단된 다발성 골수종에 대해 FDA가 승인한 첫 번째 치료 요법이 될 가능성이 있습니다.
Johnson & Johnson (NYSE:JNJ) a soumis une demande de licence biologique complémentaire (sBLA) à la FDA pour une nouvelle indication de DARZALEX FASPRO® en combinaison avec le bortezomib, la lenalidomide et la dexaméthasone (D-VRd) pour les patients nouvellement diagnostiqués atteints de myélome multiple inéligibles ou retardant une transplantation autologue de cellules souches. La soumission est basée sur l'étude de phase 3 CEPHEUS, qui a montré :
- 60,9 % des patients ont atteint une négativité de maladie résiduelle minimale (MRD) avec D-VRd
- Réduction de 43 % du risque de progression ou de décès
- Taux global de négativité pour la MRD de 60,9 % contre 39,4 % pour VRd seul
- Taux soutenu de négativité pour la MRD de 48,7 % contre 26,3 % pour VRd
- Taux de réponse complète de 81,2 % contre 61,6 % pour VRd
Le profil de sécurité était cohérent avec les profils connus pour DARZALEX FASPRO® et VRd. Cela pourrait potentiellement être le premier régime de traitement approuvé par la FDA pour le myélome multiple nouvellement diagnostiqué, basé sur la négativité de la MRD comme objectif principal.
Johnson & Johnson (NYSE:JNJ) hat einen ergänzenden Antrag auf Biologisches Lizenzverfahren (sBLA) bei der FDA für eine neue Indikation von DARZALEX FASPRO® in Kombination mit Bortezomib, Lenalidomid und Dexamethason (D-VRd) für neu diagnostizierte Patienten mit multiplem Myelom eingereicht, die für eine autologe Stammzelltransplantation nicht geeignet sind oder diese aufschieben. Der Antrag basiert auf der Phase 3-Studie CEPHEUS, die folgendes zeigte:
- 60.9% der Patienten erreichten mit D-VRd eine Negativität für minimale Resterkrankung (MRD)
- 43% Reduktion des Risikos für Progression oder Tod
- Gesamt-MRD-Negativitätsrate von 60.9% gegenüber 39.4% für VRd allein
- Nachhaltige MRD-Negativitätsrate von 48.7% gegenüber 26.3% für VRd
- Komplette Ansprechrate von 81.2% gegenüber 61.6% für VRd
Das Sicherheitsprofil war konsistent mit den bekannten Profilen für DARZALEX FASPRO® und VRd. Dies könnte möglicherweise das erste von der FDA genehmigte Behandlungsschema für neu diagnostiziertes multiples Myelom sein, das auf der MRD-Negativität als primärem Endpunkt basiert.
- 60.9% of patients achieved minimal residual disease (MRD)-negativity with D-VRd
- 43% reduction in risk of progression or death compared to VRd alone
- Overall MRD-negativity rate of 60.9% vs 39.4% for VRd alone
- Sustained MRD-negativity rate of 48.7% vs 26.3% for VRd
- Complete response rate of 81.2% vs 61.6% for VRd
- Potential to be the first FDA-approved treatment regimen for newly diagnosed multiple myeloma based on MRD-negativity as primary endpoint
- None.
Insights
The submission of an sBLA for DARZALEX FASPRO® in combination with VRd for newly diagnosed multiple myeloma (NDMM) patients is a significant development. The CEPHEUS study results are impressive, showing a 60.9
Key points to consider:
- This could be the first FDA-approved treatment based on MRD-negativity as a primary endpoint for NDMM.
- The quadruplet regimen (D-VRd) showed superior efficacy compared to the triplet (VRd) across multiple measures.
- The safety profile aligns with known profiles of DARZALEX FASPRO® and VRd.
If approved, this could potentially change the standard of care for NDMM patients ineligible for or deferring transplant. The 81.2
This regulatory submission has positive implications for Johnson & Johnson's (JNJ) oncology portfolio and potential revenue growth. Key financial considerations include:
- Expanded market opportunity: If approved, JNJ could capture a larger share of the NDMM market, particularly among non-transplant eligible patients.
- Competitive advantage: The potential first-mover status with an MRD-negativity based approval could strengthen JNJ's position against competitors.
- Revenue impact: DARZALEX is already a blockbuster drug for JNJ, generating
$7.9 billion in 2023. This new indication could further boost sales. - Long-term growth: Improved efficacy may lead to longer treatment duration, potentially increasing the lifetime value per patient.
Investors should weigh this potential against JNJ's overall portfolio diversification and the impact on the company's
Results from CEPHEUS study highlight DARZALEX FASPRO® quadruplet regimen as a potential standard of care in newly diagnosed patients regardless of transplant eligibility
New indication would be the first FDA-approved treatment regimen for newly diagnosed multiple myeloma based on a study with MRD-negativity as the primary endpoint
This submission is supported by data from the Phase 3 CEPHEUS study (NCT03652064), which showed 60.9 percent of patients achieved minimal residual disease (MRD)-negativity with D-VRd and the risk of progression or death was reduced by 43 percent. The CEPHEUS study evaluated the efficacy and safety of D-VRd compared to bortezomib, lenalidomide and dexamethasone (VRd) for NDMM patients for whom ASCT was not planned as initial therapy (transplant ineligible or deferred).1
The D-VRd regimen increased depth and durability of responses compared to VRd, including the primary endpoint of overall MRD-negativity rate (10-5) of 60.9 percent vs 39.4 percent at a median follow-up of 58.7 months (odds ratio [OR], 2.37;
"DARZALEX FASPRO-based therapies continue to be at the forefront of multiple myeloma research. We're encouraged that the FDA Oncologic Drugs Advisory Committee recently voted in favor of MRD-negativity as an acceptable endpoint in multiple myeloma trials. CEPHEUS is the first registrational study with a primary endpoint of MRD-negativity filed by Johnson & Johnson in multiple myeloma," said Craig Tendler, M.D., Vice President, Late Clinical Development and Global Medical Affairs, Innovative Medicine, Johnson & Johnson. "The data from CEPHEUS add to the body of evidence for DARZALEX FASPRO in newly diagnosed multiple myeloma and, together with the results of the PERSEUS study, demonstrate the potential benefit of this quadruplet regimen for newly diagnosed patients, regardless of transplant eligibility."
Data from CEPHEUS was presented as a late-breaking oral presentation (Abstract #OA-63) at the 2024 International Multiple Myeloma Society (IMS) Annual Meeting.
About the CEPHEUS Study
CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd vs VRd in patients with newly diagnosed multiple myeloma for whom autologous stem cell transplant (ASCT) is not planned as initial therapy. The primary endpoint is minimal residual disease (MRD)-negativity rate at a 10-5 sensitivity threshold. Key secondary endpoints include overall complete response (CR) or better rate, progression-free survival (PFS), and sustained MRD-negative rate at 1 year. The trial has enrolled 396 patients in 13 countries.
About the PERSEUS Study
The PERSEUS study (NCT03710603) is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for autologous stem cell transplant (ASCT). Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in
About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.3 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.4 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the
About DARZALEX FASPRO®
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.1 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.
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 https://www.darzalexhcp.com.
DARZALEX FASPRO® INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
- In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
- 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 (PI)
- 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 PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.
Systemic Reactions
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination,
Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.
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 daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.
Local Reactions
In this pooled safety population, injection-site reactions occurred in
Neutropenia
Daratumumab may increase neutropenia 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 FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.
Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® 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 FASPRO® and for 3 months after the last dose.
The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.
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 administration. 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 are not impacted.
Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.
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 DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥
The most common hematology laboratory abnormalities (≥
Please click here to read full Prescribing Information for DARZALEX FASPRO®.
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 www.jnj.com or at www.innovativemedicine.jnj.com. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both 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 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 Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or 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 Annual Report on Form 10-K for the fiscal year ended December 31, 2023, 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. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments.
1 Usmani, S., et al. Daratumumab SC + Bortezomib/Lenalidomide/Dexamethasone in Patients With Transplant-ineligible or Transplant-deferred Newly Diagnosed Multiple Myeloma: Results of the Phase 3 CEPHEUS Study. IMS 2024. September 27, 2024. | ||||
2 Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178 | ||||
3 National Cancer Institute. Plasma Cell Neoplasms. Accessed July 2024. Available at: https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq | ||||
4 Multiple Myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Accessed July 2024. Available at: https://www.cancercenter.com/cancer-types/multiple-myeloma | ||||
5 American Cancer Society. Myeloma Cancer Statistics. Accessed July 2024. Available at: https://cancerstatisticscenter.cancer.org/types/myeloma | ||||
6 American Cancer Society. What is Multiple Myeloma? Accessed July 2024. Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html | ||||
7 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Accessed July 2024. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html | ||||
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FAQ
What is the new indication for DARZALEX FASPRO® that JNJ is seeking FDA approval for?
What were the key results of the CEPHEUS study for JNJ's DARZALEX FASPRO®?
How does JNJ's DARZALEX FASPRO® quadruplet regimen compare to the standard triplet regimen?
What is the significance of MRD-negativity in JNJ's DARZALEX FASPRO® study for multiple myeloma?
