Business Wire

Darzalex®▼ (daratumumab) Combination Therapy Improved Clinical Outcomes Regardless of Cytogenetic Risk for Previously-Treated Patients with Multiple Myeloma

4.6.2017 19:33 | Business Wire

Jaa

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.”

#ENDS#

About Daratumumab

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.

###

References

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.

PHEM/DAR/0517/0014

June 2017

Contact information

Janssen
Media Enquiries:
Natalie Buhl, +353 (0)85-744-6696 (Mobile)
nbuhl@its.jnj.com
or
Investor Relations:
Lesley Fishman, +1 732-524-3922
or
Joseph J. Wolk, +1 732-524-1142

Tietoja julkaisijasta

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

The Valence Group Issues Fairness Opinion to SK Capital in Connection with Archroma18.8.2017 16:30Tiedote

The Valence Group has provided a fairness opinion to SK Capital Partners, LP in connection with its recapitalization of Archroma, including investments made by various affiliates of SK Capital. Terms of the transaction were not disclosed. About SK Capital SK Capital is a private investment firm focused on the specialty materials, chemicals and pharmaceutical sectors. The firm builds strong and growing businesses that generate substantial long-term value for its investors. SK Capital utilizes its industry, operating and investment experience to identify opportunities to transform businesses into higher performing companies with improved strategic positioning, growth, profitability and risk profiles. The firm currently has approximately $1.9 billion of assets under management and its portfolio companies generate revenues of over $5.0 billion annually and employ approximat

Biker Summer 2017 campaign: What’s happening during Biker Summer 2017? Moto-tyres.co.uk is giving away exciting prizes!18.8.2017 12:22Tiedote

Whether it’s a short weekend break or a long-distance tour – once again this year Moto-tyres.co.uk is asking bikers from 10 countries about their dream destinations and longest journeys as part of its “Biker Summer 2017” campaign. To ensure than nothing gets in the way of your next tour, the two-wheeler tyre store from Delticom, Europe’s leading online tyre dealer, is entering anyone who completes the survey before 30 September 2017 into a prize draw to win some great biking accessories. Simply answer three short questions about your plans for bike tours this year (don’t forget to provide your name and email address), and with a bit of luck, you might win one of these great prizes. Up for grabs are a GARMIN motorbike GPS system, a GoPro camera with helmet bracket and five 200-Pound vouchers for new motorbike tyres from the online store – thanks to the product range at Moto-tyres.co.uk, eve

Lenovo Continues to Gain Momentum in First Quarter FY 2017/1818.8.2017 03:04Tiedote

Behind the strength of its 3-wave strategy, Lenovo’s business transformation continued to gain traction during the first quarter, delivering solid profitability in its core PC and smart devices business, and revenue and profit improvements in targeted growth areas, including the data center and mobile businesses. Fueled by new investments in people and products, Lenovo’s Data Center Group (DCG) introduced the most comprehensive product lineup in its history, with the new ThinkSystem and ThinkAgile portfolio, and continued to build out its end-to-end sales organization. Similarly, Lenovo’s Mobile Business Group launched significant new products led by the Moto Z2 Force, available now on all major U.S. carriers, and ramped up its branding efforts worldwide. “In the first quarter this fiscal year, we had stable performance as we executed our 3-wave strategy with commitment. We

Spirent Tests Wi-Fi Network Performance with O2 at the Coca-Cola London Eye17.8.2017 18:57Tiedote

Spirent Communications plc (LSE:SPT), today announced its Landslide E10 network test platform has been used with O2 to validate the Wi-Fi network performance and capacity at the Coca-Cola London Eye, before the launch of a new smartphone application last month. This Smart News Release features multimedia. View the full release here: http://www.businesswire.com/news/home/20170817005758/en/ Spirent Landslide E10 helped O2 validate Wi-Fi performance and capacity at the Coca-Cola London Eye, before the launch of a new smartphone application last month. (Photo: Busines Wire) Merlin Entertainments plc, operator of the London Eye, wanted to measure its Wi-Fi network performance, to ensure its infrastructure could provide an excellent experience for users of the new app, which puts increased demands on the Wi-Fi network. “The London Eye is a global attractio

Watch BizWireTV: A Camera You Can Wear and Krispy Kreme’s Famous Donuts Get Eclipsed with Chocolate17.8.2017 15:08Tiedote

On BizWireTV, catch some Quick Biz Hits and see the latest in Star Power. Also see what’s happening in the startup world with the Accelerator Report, featuring the VC Watch and this week’s Startup Standout. This Smart News Release features multimedia. View the full release here: http://www.businesswire.com/news/home/20170817005305/en/ BizWireTV is hosted by Jordyn Rolling (Photo: Business Wire Now you can watch BizWireTV, and the latest breakthroughs in tech from the biggest brands, on any screen you want by downloading the new app through the Apple TV and iPhone App Store and Google Play for Android devices. Top of the Wire Introducing FrontRow: the camera re-invented. Watch BizWireTV to see more disruptors as well as the top 5 trending stories of the week! A core c

PsiOxus Therapeutics Announce Two New Board Appointments: New Board Appointments Strengthen Company’s US Presence17.8.2017 10:00Tiedote

PsiOxus Therapeutics, Ltd. (PsiOxus) today announced the appointment of Charles Rowland and Duncan Higgons to the Board of Directors as part of an ongoing drive to expand in the US. Charles Rowland was most recently the President and Chief Executive Officer (CEO) of Aurinia Pharmaceuticals, a clinical stage pharmaceutical company focused on the global lupus nephritis market. Prior to this, he served as the Vice President and Chief Financial Officer (CFO) of ViroPharma, during which time the company grew into a global biopharmaceutical business with $500 million in annual revenues until it was acquired by Shire plc for $4.2 billion. Before joining ViroPharma, Mr. Rowland was executive Vice President, CFO, and interim co-CEO, for Endo Pharmaceuticals. In his earlier career, Charles held finance and operational positions at Biovail Pharmaceuticals, Breakaway Technologies, Pharmacia

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