DetailsCategory: AntibodiesPublished on Saturday, 02 May 2020 12:42Hits: 149

- Innovative, fixed-dose formulation significantly reduces treatment time from hours to minutes and demonstrates consistent efficacy with a reduction in administration-related reactions compared to DARZALEX (daratumumab) for approved indications

- DARZALEX FASPRO is the only subcutaneous CD38-directed antibody approved in the treatment of multiple myeloma

HORSHAM, PA, USA I May 1, 2020 I The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the U.S. Food and Drug Administration (FDA) approved DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a new subcutaneous formulation of daratumumab. DARZALEX FASPRO is approved in four regimens across five indications in multiple myeloma patients, including newly diagnosed, transplant-ineligible patients as well as relapsed or refractory patients.As a fixed-dose formulation, DARZALEX FASPRO can be administered over approximately three to five minutes, significantly less time than DARZALEX,which is given intravenously over hours. In the Phase 3 COLUMBA study supporting the approval, DARZALEX FASPRO demonstrated a consistent overall response rate (ORR) and pharmacokinetics and a similar safety profile compared with intravenous DARZALEX in patients with relapsed or refractory multiple myeloma. In addition, there was a nearly two-thirds reduction in systemic administration-related reactions (ARRs) for DARZALEX FASPRO compared to intravenous DARZALEX (13 percent vs. 34 percent, respectively).

"This approval exemplifies Janssen's mission and commitment to bringing together passion, science and ingenuity to advance novel solutions for patients," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, LLC. "We are excited about the potential of this meaningful innovation in transforming the treatment experience for patients with multiple myeloma where DARZALEX FASPRO can be administered in approximately three to five minutes, significantly less time than intravenous DARZALEX, which is given over hours. Based on its favorable profile, we are accelerating the development of DARZALEX FASPRO and evaluating its potential in multiple ongoing studies."

Click to Tweet: #NEWS: #FDA approves subcutaneous CD38-directed antibody for the treatment of multiple #myeloma. See here for more details: https://bit.ly/2VozhzY

The approval is based on data from the Phase 3 COLUMBA (MMY3012)and Phase 2 PLEIADES (MMY2040) studies.1,2 In the COLUMBA study, the ORR was non-inferior for patients taking DARZALEX FASPROas monotherapycompared to those taking intravenous DARZALEXas monotherapy (41 percent vs. 37 percent, respectively). In addition, there were fewer systemic ARRs with DARZALEX FASPRO versus intravenous DARZALEX (13 percent vs. 34 percent, respectively). In a pooled safety population of 490 patients who received DARZALEXFASPRO as monotherapy or in combination, the ARR rate wFas 11 percent. The safety profiles of intravenous DARZALEX and DARZALEX FASPRO were otherwise similar.1 Additionally, in the Phase 2 PLEIADES study evaluating the efficacy and safety of DARZALEX FASPRO in combination therapies, objective responses were demonstrated in combination with bortezomib, melphalan and prednisone (D-VMP) in newly diagnosed transplant ineligible patients. In addition, objective responses were demonstrated in combination with lenalidomide and dexamethasone (D-Rd) in relapsed or refractory patients who received one prior line of therapy.2

"The Multiple Myeloma Research Foundation shares a common goal with Janssen in advancing treatments for multiple myeloma and addressing the unmet needs of this patient community," said Paul Giusti, President and CEO of the Multiple Myeloma Research Foundation (MMRF). "The approval of DARZALEXFASPRO marks an important milestone which will help make a positive difference in the lives of patients who depend on this effective therapy."

Click to Tweet: .@theMMRF talks about advancing treatments for multiple #myeloma and addressing patient needs with latest #FDA approval. Read more here: https://bit.ly/2VozhzY

"Since the approval of daratumumab, a robust body of evidence has established its use as a treatment for multiple myeloma in both the frontline and relapsed and refractory settings," said Saad Z. Usmani, M.D., Division Chief of Plasma Cell Disorders, Levine Cancer Institute. "With DARZALEX FASPRO there may be fewer administration-related reactions compared to intravenous DARZALEX, providing an additional treatment option that may help patients, oncologists and nursing staff."

DARZALEX FASPROis co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) [Halozyme'sENHANZEdrug delivery technology].DARZALEX FASPRO will be available to patients and physicians as soon as the week of May 11, 2020. The intravenous DARZALEX formulation will also remain available as an option for patients and their physicians.

DARZALEX FASPROis approved 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 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.

The U.S. FDA approval of DARZALEX FASPRO marks the first approval for this innovative subcutaneous formulation globally, and Janssen continues to work with health authorities around the world in an effort to bring this new treatment option to patients living with multiple myeloma.

Access to DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)Janssen offers comprehensive access and support information, resources and services to assist U.S. patients in gaining access to DARZALEX FASPROthrough the Janssen CarePath Program. Through the program, eligible commercial patients pay no more than $5 per injection, regardless of individual income level. Information on the enrollment process is available online atwww.CarePathSavingsProgram.com/DARZALEX.

For more information, healthcare providers or patients can contact: 1-844-55DARZA (1-844-553-2792). Information will also be available atwww.DARZALEX.com. Dedicated case coordinators are available to work with both healthcare providers and patients.

About the COLUMBA Study 1The randomized, open-label, multicenter Phase 3 COLUMBA study (MMY3012) included 522 patients (median age of 67 years) with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease was refractory to both a PI and an IMiD. In the arm that received DARZALEX FASPRO(n=263), patients received a fixed dose of DARZALEX FASPRO1,800 milligrams (mg), co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) 2,000 Units per milliliter (U/mL), subcutaneously weekly for Cycles 1 2, every two weeks for Cycles 3 6 and every four weeks for Cycle 7 and thereafter. In the intravenous DARZALEXarm (n=259), patients received DARZALEXfor intravenous infusion 16 milligrams per kilogram (mg/kg) weekly for Cycles 1 2, every two weeks for Cycles 3 6 and every four weeks for Cycle 7 and thereafter. Each cycle was 28 days. In the arm that received DARZALEX FASPRO, itwas given in a fixed volume of 15 mL over three to five minutes; the median injection time was five minutes. In the arm that received theintravenous administration, the median durations of the first, second and subsequent intravenous DARZALEXinfusions were 7.0, 4.3 and 3.4 hours, respectively.Patients in both arms continued treatment until disease progression or unacceptable toxicity.

About the PLEIADES Study 2The non-randomized, open-label, parallel assignment Phase 2 PLEIADES study (MMY2040) included more than 240 adults with multiple myeloma, including 67 patients with newly diagnosed multiple myeloma who were treated with 1,800 mg of DARZALEX FASPROin combination with bortezomib, melphalan, and prednisone (D-VMP) and 65 patients with relapsed or refractory disease who were treated with 1,800 mg of DARZALEX FASPROplus lenalidomide and dexamethasone (D-Rd). The primary endpoint for the D-VMP and D-Rd cohorts was overall response rate.

About DARZALEXand DARZALEX FASPROJanssen is committed to exploring the potential of DARZALEX (daratumumab) for patients with multiple myeloma across the spectrum of the disease. DARZALEX has been approved in seven indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.

DARZALEX has become a backbone therapy in the treatment of multiple myeloma, having been used in the treatment of more than 58,000 patients in the U.S. alone since its U.S. FDA approval in 2015. DARZALEX is the first CD38-directed antibody approved globally to treat multiple myeloma and in 2020, DARZALEX FASPRO(daratumumab and hyaluronidase human-fihj) follows as the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma.2

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.4 DARZALEX binds to CD38 and inhibits tumor cell growth causing myeloma cell death.5 DARZALEX may also have an effect on normal cells.3 Data across seven Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that DARZALEX-based regimens resulted in significant improvement in progression-free survival and/or overall survival. 4,5,6,7,8,9,10,11 Additional studies are underway to assess the efficacy and safety of DARZALEXFASPRO in the treatment of other malignant and pre-malignant hematologic diseases in which CD38 is expressed, including smoldering myeloma and in amyloidosis.12,13

Key DARZALEX Milestones:

Please see full Prescribing Information at http://www.DARZALEX.com.

About Multiple MyelomaMultiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.21,22When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow. In 2020, it is estimated that 32,270 people will be diagnosed and 12,830 will die from the disease in the U.S.24 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.23

Please see full Prescribing Information at http://www.DARZALEX.com.

About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at http://www.janssen.com. Follow us at http://www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

ENHANZEis a registered trademark of Halozyme.

1Mateos M-V et al. Efficacy and Safety of the Randomized, Open-Label, Non-inferiority, Phase 3 Study of Subcutaneous (SC) Versus Intravenous (IV) Daratumumab (DARA) Administration in Patients (pts) With Relapsed or Refractory Multiple Myeloma (RRMM): COLUMBA. 2019 American Society of Clinical Oncology Annual Meeting. June 2019.

2Janssen Research & Development, LLC. A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.

32020Fedele G et al. CD38 Ligation in Peripheral Blood Mononuclear Cells of Myeloma Patients Induces Release of Protumorigenic IL-6 and Impaired Secretion of IFN Cytokines and Proliferation. Mediators Inflamm. 2013;564687.

4Janssen Research & Development, LLC. A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009?term=mmy3003&rank=1 Identifier: NCT02136134 .

5Janssen Research & Development, LLC. Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134?term=mmy3004&rank=1 Identifier: NCT02076009.

6Janssen Research & Development, LLC. A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383?term=mmy3006 Identifier: NCT02541383.

7Janssen Research & Development, LLC. A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479?term=mmy3007&rank=1 Identifier: NCT02195479.

8Janssen Research & Development, LLC. Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=mmy3008&rank=1 Identifier: NCT02252172.

9Janssen Research & Development, LLC. A Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-Dose Therapy (Asia Pacific Region). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812?term=MMY3011&rank=1 Identifier: NCT03217812.

10European Myeloma Network. Compare Progression Free Survival Btw Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03180736?term=MMY3013&rank=2 Identifier: NCT03180736

11Amgen. Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1 Identifier: NCT03158688.

12Janssen Research & Development, LLC. A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 March 19]. Available at: https://clinicaltrials.gov/ct2/show/NCT02316106?term=smm2001&rank=1 Identifier: NCT02316106.

13Janssen Research & Development, LLC. An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 March 19]. Available at: https://clinicaltrials.gov/ct2/show/NCT02413489?term=lym2001&rank=1 Identifier: NCT02413489

14Janssen Biotech, Inc. "Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab." Issued August 30, 2012.

15Janssen Biotech, Inc. "DARZALEX (daratumumab) Approved by U.S. FDA: First Human Anti-CD38 Monoclonal Antibody Available for the Treatment of Multiple Myeloma." Issued November 16, 2015.

16Janssen Biotech, Inc. "DARZALEX (daratumumab) Approved by U.S. FDA in Combination with Two Standard of Care Regimens for the Treatment of Patients with Multiple Myeloma Who Have Received At Least One Prior Therapy." Issued November 21, 2016.

17Janssen Biotech, Inc. "DARZALEX (daratumumab) Approved by the U.S. FDA in Combination with Pomalidomide and Dexamethasone for Patients with Multiple Myeloma Who Have Received At Least Two Prior Therapies." Issued June 16, 2017.

18Janssen Biotech, Inc. "Janssen Announces DARZALEX (daratumumab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible." Issued May 7, 2018.

19Janssen Biotech, Inc. "Janssen Announces U.S. FDA Approval of DARZALEX (daratumumab) in Combination with Lenalidomide and Dexamethasone for Newly Diagnosed Patients with Multiple Myeloma Who Are Transplant Ineligible." Issued June 27, 2019.

20Janssen Biotech, Inc. "Janssen Announces U.S. FDA Approval of DARZALEX (daratumumab) Combination Regimen for Newly Diagnosed, Transplant-Eligible Patients with Multiple Myeloma." Issued September 26, 2019.

21Kumar, SK et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012 Jan; 26(1):149-57.

22American Cancer Society. "What Is Multiple Myeloma?" Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed June 2019.

23American Cancer Society. "Key Statistics About Multiple Myeloma." Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed January 2020.

SOURCE: Janssen

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US Food and Drug Administration Approves DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a New Subcutaneous Formulation of Daratumumab in the...

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