Johnson & Johnson submits supplemental Biologics License Application to U.S. FDA seeking approval of DARZALEX FASPRO based regimen for the treatment of patients with transplant-eligible, newly diagnosed multiple myeloma

2024-01-31

临床3期临床结果上市批准引进/卖出ASH会议

Data supporting the application showed the addition of DARZALEX FASPRO® to lenalidomide, bortezomib and dexamethasone (VRd) induction and consolidation and lenalidomide maintenance therapy reduced the risk of progression or death by 58 percent compared to standard of care

If approved, the DARZALEX FASPRO®-based regimen has the potential to provide an effective quadruplet therapy for many patients with newly diagnosed multiple myeloma who are eligible for transplant

RARITAN, NJ, USA I January 30, 2024 I Johnson & Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new indication for DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for induction and consolidation treatment and with lenalidomide (D-R) for maintenance treatment of adult patients who are newly diagnosed with multiple myeloma (NDMM) and are eligible for autologous stem cell transplant (ASCT).

This submission is supported by data from the Phase 3 PERSEUS (NCT03710603) study evaluating D-VRd induction and consolidation therapy, ASCT, and D-R maintenance therapy, compared to bortezomib, lenalidomide and dexamethasone (VRd), ASCT, and lenalidomide (R) maintenance. Results from the primary analysis showed that the study met its primary endpoint of progression-free survival (PFS), reducing the risk of disease progression or death by 58 percent (Hazard Ratio [HR], 0.42; 95 percent Confidence Interval [CI] 0.30-0.59; P1 Treatment with D-VRd and ASCT followed by D-R maintenance also increased the depth of response with higher rates of complete response (CR) or better, stringent complete response (sCR) and minimal residual disease (MRD) negativity compared to treatment with VRd, ASCT and R maintenance. Overall, 64 percent of patients who entered the maintenance phase in the D-VRd arm were able to discontinue treatment with DARZALEX FASPRO® after achieving a complete response or better and sustained MRD-negativity following at least two years of D-R maintenance in accordance with the protocol. The overall safety profile of D-VRd followed by D-R maintenance was consistent with the known safety profiles for DARZALEX FASPRO®, VRd and R.

"We are committed to changing the course of multiple myeloma through building combination regimens such as D-VRd with complementary mechanisms of action. The DARZALEX FASPRO-based quadruplet therapy demonstrated a clinically significant reduction in the risk of progression or death for transplant-eligible, newly diagnosed patients with multiple myeloma," said Craig Tendler, M.D., Vice President, Clinical Development, Diagnostics, and Global Medical Affairs, Johnson & Johnson Innovative Medicine. "Patients are most likely to experience their deepest and most durable responses during the first line of treatment with D-VRd. This regimen has the potential to improve long-term outcomes for newly diagnosed patients and we look forward to working with the FDA on the review of this application."

Data from the PERSEUS study were presented as a late-breaking oral presentation (LBA–1) at the 2023 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine.

About the PERSEUS study

The PERSEUS study is being conducted in collaboration with the European Myeloma Network Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd and ASCT followed by D-R maintenance vs VRd and ASCT followed by R maintenance in patients with transplant-eligible NDMM. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, overall MRD-negativity (in patients with CR or better), and overall survival. DARZALEX FASPRO® was discontinued after at least 24 months of D-R maintenance therapy in patients who had a CR or better and had sustained MRD–negative status for at least 12 months. 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 Europe and Australia.

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 U.S. and more than 12,000 will die from the disease.5 People with multiple myeloma have a 5-year survival rate of 59.8 percent.5 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, kidney problems or infections.6,7

About DARZALEX FASPRO®

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.8 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.

INDICATIONS

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

For more information, visit www.DARZALEX.com.

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.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.

1 Pieter Sonneveld, Dimopoulos MA, Boccadoro M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. The New England Journal of Medicine. Published online December 12, 2023. doi:https://doi.org/10.1056/nejmoa2312054

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 January 17, 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 January 17, 2024. https://www.cancercenter.com/cancer-types/multiple-myeloma

5 American Cancer Society. Myeloma Cancer Statistics. Accessed January 17, 2024. Available at: https://cancerstatisticscenter.cancer.org/types/myeloma

6 American Cancer Society. What is Multiple Myeloma? Accessed January 17, 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 January 17, 2024. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html

8 DARZALEX FASPRO® Prescribing Information, November 2022.

SOURCE: Johnson & Johnson