Darzalex®▼ (daratumumab) Combination Therapy Improved Clinical Outcomes Regardless of Cytogenetic Risk for Previously-Treated Patients with Multiple Myeloma
Janssen-Cilag International NV (“Janssen”) today announced new data from updated analyses of the pivotal Phase 3 CASTOR and POLLUX clinical studies, demonstrating that Darzalex®▼ (daratumumab) in combination with Velcade® (bortezomib) and dexamethasone, or lenalidomide and dexamethasone, improved progression-free survival (PFS) and the overall response rate (ORR) for previously-treated patients with multiple myeloma, regardless of cytogenetic risk.1,2 These data will be featured as an oral presentation at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting on Sunday, June 4 at 11:45 a.m. CDT.1
Additionally, data from the Phase1b MMY1001 study showed the potential of daratumumab in combination with carfilzomib, lenalidomide and dexamethasone (KRd) for newly diagnosed patients with multiple myeloma.3,4 These data represent the first assessment of daratumumab in combination with a next generation proteasome inhibitor (PI) and an immunomodulatory agent earlier in the treatment paradigm of multiple myeloma. The data are being presented as an oral presentation from 9:45 – 9:57 a.m. CDT on Sunday, June 4.3 These data will also be featured in the Best of ASCO program, which aims to highlight the most cutting-edge science and education from the ASCO Annual Meeting.5
“These findings from the Phase 3 CASTOR and POLLUX trials show daratumumab delivered deep and durable responses for previously-treated patients, regardless of cytogenetic risk,” said Dr. Katja Weisel, Associate Professor, Department of Haematology and Oncology, University Hospital of Tuebingen, Tuebingen, Germany. “Daratumumab appeared to improve poor outcomes associated with high risk cytogenetics, and these data support its consistent clinical benefit in combination with two of the most widely used treatment classes.”
Updated data from those two Phase 3 clinical trials support the addition of daratumumab to standard of care regimens for previously-treated patients regardless of cytogenetic risk:1
According to follow-up data from the CASTOR study, daratumumab (D), in
combination with bortezomib (a PI) and dexamethasone (Vd),
significantly reduced the risk of disease progression or death by 55%
(Hazard Ratio [HR]=0.45; 95% CI [0.25-0.80]; p=0.0053) in patients
with high risk cytogenetics (n=44) compared to Vd alone (n=51).1
Additionally, in patients with high risk cytogenetics the daratumumab
combination regimen resulted in an ORR of 82% vs. 62% (p=0.2028), with
very good partial response (VGPR) or better achieved in 64% vs. 35% of
patients, and CR or better achieved in 34% vs. 9% of patients.1
- In patients with standard cytogenetic risk, the addition of daratumumab reduced the risk of disease progression or death by 74% (n=123; HR=0.26; 95% CI [0.18-0.37]; p<0.0001) compared to Vd alone (n=135).1 Additionally, the daratumumab combination regimen resulted in an ORR of 85% vs. 64% (p=0.0001), with VGPR or better achieved in 64% vs. 26% of patients, and CR or better achieved in 28% vs. 8% of patients treated with DVd vs. Vd, respectively. The median duration of follow-up was 19.4 months.1
According to follow-up data from the POLLUX study, daratumumab (D), in
combination with lenalidomide (an immunomodulatory agent) and
dexamethasone (Rd), reduced the risk of disease progression or death
by 47% (HR=0.53; 95% CI [0.25-1.13]; p=0.0921) in patients with high
risk cytogenetics (n=28) compared to Rd alone (n=37).1
Additionally, in patients with high risk cytogenetics the daratumumab
combination regimen resulted in an ORR of 85% vs. 67% (p=0.0435), with
VGPR or better achieved in 64%1 vs. 31% of patients, and CR
or better achieved in 38% vs. 6% of patients.1
- In patients with standard cytogenetic risk, the addition of daratumumab reduced the risk of disease progression or death by 70% (n=133; HR=0.30; 95% CI [0.20-0.47]; p<0.0001) compared to Rd alone (n=113).1 Additionally, the daratumumab combination regimen resulted in an ORR of 95% vs. 82% (p=0.0004), with VGPR or better achieved in 85% vs. 55% of patients, and CR or better achieved in 58% vs. 27% of patients treated with DRd vs. Rd, respectively.1 The median duration of follow-up was 25.4 months.1
A cohort in the Phase 1b MMY1001 EQUULEUS study showed that the overall safety profile of daratumumab (D) in combination with carfilzomib, lenalidomide and dexamethasone (KRd) in patients with newly diagnosed multiple myeloma was consistent with the known safety profiles of D and KRd, respectively.3 Serious treatment-emergent adverse events (TEAEs) such as pyrexia, influenza and pulmonary embolism, occurred in 46% of patients, 14% of which were potentially daratumumab-related.3 The most common Grade 3/4 haematologic TEAEs (≥30%) were lymphopenia (64%) and neutropenia (14%).3 Treatment with this daratumumab combination regimen yielded promising results with an ORR (≥partial response) of 100%, with 91% achieving VGPR or better and 43% achieving CR or better, after a short-term follow up.3
“These results, along with other data for daratumumab at ASCO, demonstrate its potential as a foundational therapy for multiple myeloma in combination with standard of care regimens for patients across different stages of their disease,” said Dr Catherine Taylor, Haematology Therapeutic Area Lead, Janssen Europe, Middle East and Africa (EMEA). “We are especially excited by the early data for daratumumab in newly diagnosed patients, which show promise for the future of daratumumab in the frontline setting.”
Daratumumab is a first-in-class biologic targeting CD38, a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.6,7,8
On April 28, 2017 the European Commission (EC) approved a broadening of the existing Marketing Authorisation for daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy.9 The first EC approval for daratumumab was received on May 23, 2016.
The EC initially granted conditional approval to daratumumab as monotherapy for the treatment of adult patients with relapsed and refractory MM, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. Following recommendation from the EC, daratumumab in monotherapy has now transitioned from conditional approval to full marketing authorisation.9
Daratumumab induces rapid tumour cell death through apoptosis (programmed cell death)7,10 and multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).7,11,12 Daratumumab has also demonstrated immunomodulatory effects that contribute to tumour cell death via a decrease in immune suppressive cells including T-regs, B-regs and myeloid-derived suppressor cells.7,13 Daratumumab is being evaluated in a comprehensive clinical development programme that includes five Phase 3 studies across a range of treatment settings in multiple myeloma. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases in which CD38 is expressed. For more information, please see www.clinicaltrials.gov.
For further information on daratumumab, please see the Summary of Product Characteristics at https://www.medicines.org.uk/emc/medicine/32088.
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab.
About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.14 MM is the second most common form of blood cancer, with around 39,000 new cases worldwide in 2012.15 MM most commonly affects people over the age of 65 and is more common in men than in women.16 The most recent five-year survival data for 2000-2007 show that across Europe, up to half of newly diagnosed patients do not reach five-year survival.17 Almost 29% of patients with MM will die within one year of diagnosis.18
Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure. While some patients with MM have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.19 Patients who relapse after treatment with standard therapies, including PIs and immunomodulatory agents, have poor prognoses and few treatment options available.20
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding the potential of daratumumab and expectations for its further development. 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-Cilag International NV, any of the other Janssen Pharmaceutical Companies 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 January 1, 2017, including under “Item 1A. Risk Factors,” its most recently filed Quarterly Report on Form 10-Q, including under the caption “Cautionary Note Regarding Forward-Looking Statements,” and the company's subsequent 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 the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
1. Weisel KC, San Miguel J, Cook G, et al. Efficacy of Daratumumab in Combination with Lenalidomide Plus Dexamethasone (DRd) or Bortezomib Plus Dexamethasone (DVd) in Relapsed or Refractory Multiple Myeloma (RRMM) Based on Cytogenetic Risk Status (Abstract #8006). To be presented at ASCO Annual Meeting, Chicago, IL, USA, 2-6 June 2017.
2. Weisel KC, San Miguel J, Cook G, et al. Efficacy of Daratumumab in Combination with Lenalidomide Plus Dexamethasone (DRd) or Bortezomib Plus Dexamethasone (DVd) in Relapsed or Refractory Multiple Myeloma (RRMM) Based on Cytogenetic Risk Status. Abstract 8006. Available at: http://abstracts.asco.org/199/AbstView_199_192466.html. Last accessed June 2017
3. Jakubowiak AJ, Chari A, Lonial S, et al. Daratumumab (DARA) in Combination with Carfilzomib, Lenalidomide, and Dexamethasone (KRd) in Patients (pts) With Newly Diagnosed Multiple Myeloma (MMY1001): an Open-label, Phase 1b Study. (Abstract #8000). To be presented at ASCO Annual Meeting, Chicago, IL, USA, 2-6 June 2017.
4. Jakubowiak AJ, Chari A, Lonial S, et al. Daratumumab (DARA) in Combination with Carfilzomib, Lenalidomide, and Dexamethasone (KRd) in Patients (pts) With Newly Diagnosed Multiple Myeloma (MMY1001): an Open-label, Phase 1b Study. Abstract #8000. Available at: http://abstracts.asco.org/199/AbstView_199_190399.html. Last accessed June 2017
5. American Society of Clinical Oncology. Best of ASCO 2017 Annual Meeting. New Orleans, LA, USA, 28-29 July 2017. Available at: https://central-boa.asco.org/program Last accessed June 2017.
6. Fedele G, di Girolamo M, Recine U, et al. CD38 ligation in peripheral blood mononuclear cells of myeloma patients induces release of protumorigenic IL-6 and impaired secretion of IFNgamma cytokines and proliferation. Mediat Inflamm. 2013;2013:564687.
7. Lin P, Owens R, Tricot G, et al. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121:482-8.
8. Santoconito AM, Consoli U, Bagnato S, et al. Flow cytometric detection of aneuploid CD38++ plasmacells and CD19+ B-lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients. Leuk Res. 2004;28:469-77.
9. European Medicines Agency. DARZALEX summary of product characteristics, May 2016. Available at: https://www.medicines.org.uk/emc/medicine/32088 Last accessed June 2017.
10. Overdijk MB, Jansen JH, Nederend M, et al. The therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via Fcy receptor-mediated cross-linking. J Immunol. 2016;197:807-13.
11. de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840-8.
12. OverdijkMB, Verploegen S, Bögels M, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7:311-21.
13. Krejcik J, Casneuf T, Nijhof IS, et al. Daratumumab depletes CD38+ immune-regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 2016;128:384-94.
14. American Society of Clinical Oncology. Multiple myeloma: overview. Available at: http://www.cancer.net/cancer-types/multiple-myeloma/overview Last accessed June 2017.
15. GLOBOCAN 2012. Multiple myeloma. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=62968&Textp=Europe&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=13&type=0&window=1&submit=%C2%A0Execute Last accessed June 2017.
16. American Cancer Society. Multiple myeloma: causes, risk factors and prevention. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8739.00.pdf Last accessed June 2017.
17. De Angelis R, Minicozzi P, Sant M, et al. Survival variations by country and age for lymphoid and myeloid malignancies in Europe 2000-2007: results of EUROCARE-5 population-based study. Eur J Cancer. 2015;51:2254-68.
18. Costa LJ, Gonsalves WI, Kumar SK. Early mortality in multiple myeloma. Leukemia. 2015;29:1616-8.
19. American Cancer Society. Multiple myeloma: early detection, diagnosis and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf Last accessed June 2017.
20. Kumar SK, Lee JH, Lahuerta JJ, 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;26:149-57.
Natalie Buhl, +353 (0)85-744-6696 (Mobile)
Lesley Fishman, +1 732-524-3922
Joseph J. Wolk, +1 732-524-1142
For more than 50 years, Business Wire has been the global leader in press release distribution and regulatory disclosure.
Tilaa tiedotteet sähköpostiisi
Haluatko tietää asioista jo ennen kuin ne uutisoidaan? Kun tilaat tiedotteemme tältä julkaisijalta, saat ne sähköpostiisi yhtä aikaa suomalaisen median kanssa. Tilauksen voit halutessasi perua milloin tahansa.
Lue lisää julkaisijalta Business Wire
Logitech Delivers Strong Q2 Sales and Profit Growth24.10.2017 04:00 | Tiedote
Logitech International (SIX: LOGN) (Nasdaq: LOGI) today announced financial results for the second quarter of Fiscal Year 2018. Q2 sales were $634 million, up 12 percent in US dollars and 11 percent in constant currency, compared to Q2 of the prior year. Q2 GAAP operating income grew 12 percent to $60 million, compared to $53 million in the same quarter a year ago. Q2 GAAP earnings per share (EPS) grew 21 percent to $0.34, compared to $0.28 in the same quarter a year ago. Q2 non-GAAP operating income grew 12 percent to $72 million, compared to $65 million in the same quarter a year ago. Q2 non-GAAP EPS grew 14 percent to $0.40, compared to $0.35 in the same quarter a year ago. “We delivered another strong quarter of growth,” said Bracken Darrell, Logitech president and chief executive officer. “Gaming and Video
Proton OnSite Has Been Awarded a Contract for Approximately USD 1.8 Million and Assumes the Lead Role in the US Government Advanced Water Splitting Benchmarking Project24.10.2017 00:02 | Tiedote
Proton OnSite (Proton), a wholly owned subsidiary of Nel ASA, Oslo Norway (Nel, OSE:NEL) has been awarded a contract for approximately USD 1.8 million to participate in the US Department of Energy’s (DOE’s) Advanced Water Splitting Benchmarking Project. This is a critical piece of DOE’s HydroGEN Energy Materials Network (EMN) consortium, which was launched to accelerate the discovery and development of materials for low cost hydrogen production, enabling energy storage, resiliency and economic opportunities across sectors. Proton will work with DOE National Laboratories and lead a team to ensure that all experimental results across the water splitting research community are properly vetted, standards are set for comparison, and roadmaps are developed including research priorities and capability needs. Kathy Ayers, Proton’s Vice President of Research and Development, has been named overall project
SES Networks Works with Project Loon to Restore Connectivity in Puerto Rico23.10.2017 20:14 | Tiedote
SES Networks' high throughput and fibre-like satellite connectivity service, the stratospheric balloons operated by X, Alphabet’s self-described “moonshot factory”, and local telecommunications expertise are playing a key role in restoring 4G/LTE connectivity in disaster-affected Puerto Rico, SES announced today. This press release features multimedia. View the full release here: http://www.businesswire.com/news/home/20171023006165/en/ SES Networks Works with Project Loon to Restore Connectivity in Puerto Rico (Photo: Business Wire) The connectivity is powered by Project Loon's targeted cell coverage and SES Networks' O3b FastConnect, a rapidly deployable satellite terminal delivering fibre-like performance. Together with local technology partners, SES Networks and X are providing reliable high-performance connectivity to Puerto Ricans whose lives have been dev
Sagemcom Unveils the Next-Generation Multi-Gigabit Solutions23.10.2017 19:05 | Tiedote
AFTER THE SUCCESS OF ITS ONE GIGABIT GATEWAY RANGE, SAGEMCOM RELEASES TO THE OPERATORS THE NEXT GENERATION MULTI-GIGABIT GATEWAYS – VDSL 35B / G.FAST / PON, 2.5G/10G PON, DOCSIS 3.1 – INTEGRATING HIGH EFFICIENCY 802.11AX Wi-Fi, IN ADDITION TO NEW SMART HOME CONNECTIVITY SOLUTIONS INCLUDING DISTRIBUTED WI-FI, VOICE CONTROL AND HOME AUTOMATION. The VDSL 35B / G.fast / FTTH / PON universal gateway, F@st 5380, integrates G.fast 212MHz, GPON and 802.11ax Wi-Fi, enabling the operators to deliver Multi-Gigabit end-to-end services, and to meet the growing bandwidth required by the end-users. F@st 5380 benefits from the last innovations of the in-house field proven Sagemcom SWANTM software suite including big data, Wi-Fi distribution, smart diagnostics… The next generation Fiber gateways range includes two products: F@st 5688ax for 10G PON (XGS-PON
Moody’s Analytics Launches the CreditLens™ Platform23.10.2017 18:43 | Tiedote
Moody’s Analytics has launched the CreditLens platform, our next-generation credit origination and risk monitoring solution. This new platform offers flexibility, configurability, and efficiency to lending institutions striving to establish smarter and leaner loan origination practices. The CreditLens platform reduces time-to-decision while tapping into powerful models and insightful analytics that help lenders manage risk and drive productivity. Lenders gain efficiency from the solution’s automated spreading capability and a flexible model authoring module. They also gain deep insights from built-in Moody’s Analytics Risk Grading features and Business Insights dashboards, which provide a complete view of the lender’s credit relationships. Automation in the platform also reduces errors and preserves data lineage throughout the credit assessment and origination process.
Knopp Biosciences Announces Renewal of NIH Blueprint Grant Award for Advancing KCNQ2 Modulators in Epilepsy23.10.2017 18:11 | Tiedote
Knopp Biosciences LLC today announced the renewal and expansion of its grant award from the National Institutes of Health Blueprint Neurotherapeutics Network to advance novel treatments for epilepsy. The Phase 2 award under the NIH Small Business Innovation Research (SBIR) program anticipates NIH support of up to $2 million over the next three years of the project, subject to satisfactory completion of milestones. The renewal follows the successful completion of all milestones under a previously awarded Phase 1 grant of $400,000. Knopp is directing its potassium channel activator program to preclinical and clinical development of small-molecule drug candidates against a validated, anti-seizure pharmaceutical target encoded by the KCNQ2 gene. Knopp intends to advance novel, small-molecule KCNQ2 activators in neonatal epileptic encephalopathy, a rare disorder caused by inherit
Uutishuoneessa voit lukea tiedotteitamme ja muuta julkaisemaamme materiaalia. Löydät sieltä niin yhteyshenkilöidemme tiedot kuin vapaasti julkaistavissa olevia kuvia ja videoita. Uutishuoneessa voit nähdä myös sosiaalisen median sisältöjä. Kaikki STT Infossa julkaistu materiaali on vapaasti median käytettävissä.Tutustu uutishuoneeseemme