Study Investigating Darzalex®▼ (daratumumab) Shows Improved Depth of Response and Progression-Free Survival in Patients with Newly Diagnosed Multiple Myeloma Who are Eligible for a Transplant

• Pivotal Phase 3 data presented in ASCO oral session and
simultaneously published in The Lancet

• The Phase 3 CASSIOPEIA study is one of the largest
transplant studies ever conducted in multiple myeloma, and the largest
study conducted with daratumumab to date

BEERSE, Belgium–(BUSINESS WIRE)–The Janssen Pharmaceutical Companies of Johnson & Johnson announced
today results from the Phase 3 CASSIOPEIA (MMY3006,
NCT02541383) study, an Intergroupe Francophone du Myelome (IFM) study in
collaboration with the Dutch-Belgian Cooperative Trial Group for
Hematology Oncology (HOVON) and Janssen Research & Development, LLC.,
showing that the addition of Darzalex^® (daratumumab) to
bortezomib, thalidomide and dexamethasone (VTd) before and after
autologous stem cell transplantation (ASCT) resulted in higher response
rates and longer progression-free survival (PFS) compared to VTd alone
in patients with newly diagnosed multiple myeloma (Abstract
#8003).¹

The data, being presented for the first time as part of an oral session
at the 55th American Society of Clinical Oncology (ASCO) Annual Meeting
in Chicago, have also been simultaneously published in The
Lancet.

“CASSIOPEIA is the first study to investigate the clinical benefit of
daratumumab in combination with a standard of care treatment regimen in
patients with newly diagnosed multiple myeloma undergoing autologous
stem cell transplant,” said Dr Philippe Moreau, CASSIOPEIA primary
investigator and Head of the Hematology Department at the University
Hospital of Nantes, France. “There is a need for new treatment options
for newly diagnosed patients, potentially including this combination
therapy with daratumumab. This study adds to the growing body of
evidence for daratumumab in the frontline setting.”

The Phase 3 CASSIOPEIA trial is a two-part study. Results from this
first part of the trial showed that after consolidation, the stringent
complete response (sCR) rate was significantly higher in the
daratumumab-VTd arm (29 percent) compared to VTd alone (20 percent)
(Odds Ratio [OR] = 1.60; 95 percent confidence interval [CI], 1.21-2.12;
P<0.0010).¹ At a median follow-up of 18.8 months, PFS was
significantly improved in the daratumumab-VTd group compared to VTd
alone (Hazard Ratio [HR] = 0.47; 95 percent CI, 0.33-0.67; P<0.0001),
and the median PFS was not reached in either arm.² The
addition of daratumumab to VTd resulted in an 18-month PFS rate of 93
percent compared to 85 percent for VTd alone.¹

Daratumumab-VTd increased the rate of very good partial response or
better (83 percent vs. 78 percent) (OR = 1.41; 95 percent CI, 1.04-1.92;²
P = 0.0239) and complete response or better (39 percent vs. 26 percent)
(OR = 1.82; 95 percent CI, 1.40-2.36;² P<0.0001) compared to
VTd alone, respectively.¹ Daratumumab-VTd resulted in a
higher rate of minimal residual disease (MRD) negativity at a
sensitivity threshold of 10^–5 compared to VTd
post-consolidation (64 percent vs. 44 percent, respectively).¹

The most common (≥10%) Grade 3/4 treatment-emergent adverse events
(TEAEs) for daratumumab-VTd and VTd, respectively, were neutropenia (28
percent vs. 15 percent), lymphopenia (17 percent vs. 10 percent),
stomatitis (13 percent vs. 16 percent) and thrombocytopenia (11 percent
vs. 7 percent).¹ In the daratumumab-VTd combination arm,
infusion-related reactions occurred in 35 percent of patients.¹

“We are incredibly excited by these results, which highlight the benefit
daratumumab could offer to transplant-eligible newly diagnosed multiple
myeloma patients, and we continue to follow patients closely in part two
of the study,” said Dr Patrick Laroche, Europe, Middle East and Africa
(EMEA) Haematology Therapeutic Area Lead, Janssen-Cilag France. “These
data formed the basis for recent regulatory submissions to both the
European Medicines Agency and U.S. Food and Drug Administration, seeking
to expand the current indication for daratumumab. We are now working
closely with health authorities to bring this important combination to
patients who need new options, as soon as possible.”

ENDS

In Europe, daratumumab is indicated:³

• in combination with bortezomib, melphalan and prednisone for the
  treatment of adult patients with newly diagnosed multiple myeloma who
  are ineligible for autologous stem cell transplant
• as monotherapy for the treatment of adult patients with relapsed and
  refractory multiple myeloma, whose prior therapy included a proteasome
  inhibitor and an immunomodulatory agent and who have demonstrated
  disease progression on the last therapy
• in combination with lenalidomide and dexamethasone, or bortezomib and
  dexamethasone, for the treatment of adult patients with multiple
  myeloma who have received at least one prior therapy.

About the CASSIOPEIA Trial⁴

The randomised, open-label, multicentre, Phase 3 study is sponsored by
the French Intergroupe Francophone du Myelome in collaboration with the
Dutch-Belgian Cooperative Trial Group for Hematology Oncology and
Janssen Research & Development, LLC. The study included 1,085 newly
diagnosed patients with previously untreated, symptomatic multiple
myeloma who were eligible for high-dose chemotherapy and stem cell
transplant. In the first part of the study, patients were randomised to
receive induction treatment with VTd alone or in combination with
daratumumab, high-dose therapy and ASCT, and consolidation therapy with
VTd alone or in combination with daratumumab. The primary endpoint in
this part of the study is the proportion of patients who achieve an sCR
100 days after transplant. In the second part of the study, which is
ongoing, patients who achieved a partial response or better in part one
will undergo a second randomisation to receive maintenance treatment
with daratumumab 16 mg/kg every eight weeks for up to two years or will
be observed with no further treatment. The primary endpoint in this part
of the study is PFS.

About daratumumab

Daratumumab is a first-in-class⁵ biologic targeting CD38, a
surface protein that is highly expressed across multiple myeloma cells,
regardless of disease stage.⁶ Daratumumab is believed to
induce tumour cell death through multiple immune-mediated mechanisms of
action, including complement-dependent cytotoxicity (CDC),
antibody-dependent cell-mediated cytotoxicity (ADCC) and
antibody-dependent cellular phagocytosis (ADCP), as well as through
apoptosis, in which a series of molecular steps in a cell lead to its
death.³ A subset of myeloid derived suppressor cells (CD38+
MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were
decreased by daratumumab.³ Daratumumab is being evaluated in
a comprehensive clinical development programme across a range of
treatment settings in multiple myeloma, such as in frontline and
relapsed settings.^{4,7,8,9,10,11,12,13} Additional studies are
ongoing or planned to assess its potential in other malignant and
pre-malignant haematologic diseases in which CD38 is expressed, such as
smouldering myeloma.^14,15 For more information, please see www.clinicaltrials.gov.

For further information on daratumumab, please see the Summary of
Product Characteristics at https://www.ema.europa.eu/documents/product-information/darzalex-epar-product-information_en.pdf.

In August
2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide
agreement, which granted Janssen an exclusive licence to develop,
manufacture and commercialise daratumumab.¹⁶

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.¹⁷ In Europe, more than 48,200 people were diagnosed
with MM in 2018, and more than 30,800 patients died.¹⁸ Almost
60 percent of patients with MM do not survive more than five years after
diagnosis.¹⁹

Although treatment may result in remission, unfortunately, patients will
most likely relapse as there is currently no cure.²⁰
Refractory MM is when a patient’s disease progresses within 60 days of
their last therapy.^21,22 Relapsed cancer is when the disease
has returned after a period of initial, partial or complete remission.²³
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.²⁴ Patients
who relapse after treatment with standard therapies, including
proteasome inhibitors and immunomodulatory agents, have poor prognoses
and few treatment options available.²⁵

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 www.janssen.com/emea.
Follow us at www.twitter.com/janssenEMEA
for our latest news. Janssen Biotech, Inc., Janssen-Cilag France and
Janssen Research & Development, LLC are part of the Janssen
Pharmaceutical Companies of Johnson & Johnson.

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
benefits of daratumumab for the treatment of patients with multiple
myeloma. 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 materialise, actual results could vary materially
from the expectations and projections of Janssen Research & Development,
LLC, Janssen-Cilag France and 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 behaviour
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 30, 2018, including in the sections
captioned “Cautionary Note Regarding Forward-Looking Statements” and
“Item 1A. Risk Factors,” and in the company’s most recently filed
Quarterly Report on Form 10-Q, 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. Neither the Janssen Pharmaceutical
Companies of Johnson & Johnson nor Johnson & Johnson undertakes to
update any forward-looking statement as a result of new information or
future events or developments.

¹ Moreau P, Attal M, Hulin C, et al. Phase 3 randomized study
of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) vs
VTd in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM):
CASSIOPEIA Part 1 results. Presented at Annual Meeting of the American
Society of Clinical Oncology (ASCO), Chicago, IL, USA, 31 May – 4 June
2019.

² Moreau P, Attal M, Hulin C, et al. Phase 3 randomized study
of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) vs
VTd in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM):
CASSIOPEIA Part 1 results. Presented at Annual Meeting of the American
Society of Clinical Oncology (ASCO), Chicago, IL, USA, 31 May – 4 June
2019: abstract 8003.

³ European Medicines Agency. DARZALEX summary of product
characteristics, January 2019. Available at: https://www.ema.europa.eu/documents/product-information/darzalex-epar-product-information_en.pdf
Last accessed May 2019.

⁴ ClinicalTrials.gov. A study to evaluate daratumumab in
transplant eligible participants with previously untreated multiple
myeloma (Cassiopeia). NCT02541383. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383
Last accessed May 2019.

⁵ Sanchez L, et al. Daratumumab: a first-in-class CD38
monoclonal antibody for the treatment of multiple myeloma. J Hematol
Oncol. 2016 Jun 30;9(1):51. doi: 10.1186/s13045-016-0283-0.

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 ClinicalTrials.gov. A study comparing daratumumab,
lenalidomide, and dexamethasone with lenalidomide and dexamethasone in
relapsed or refractory multiple myeloma. NCT02076009. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009
Last accessed May 2019.

⁸ ClinicalTrials.gov. Addition of daratumumab to combination
of bortezomib and dexamethasone in participants with relapsed or
refractory multiple myeloma. NCT02136134. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134
Last accessed May 2019.

⁹ ClinicalTrials.gov. 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. NCT02195479. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479
Last accessed May 2019.

¹⁰ ClinicalTrials.gov. Study comparing daratumumab,
lenalidomide, and dexamethasone with lenalidomide and dexamethasone in
participants with previously untreated multiple myeloma. NCT02252172.
Available at: https://clinicaltrials.gov/ct2/show/NCT02252172
Last accessed May 2019.

¹¹ ClinicalTrials.gov. 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).
NCT03217812. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812
Last accessed May 2019.

¹² ClinicalTrials.gov. Comparison of pomalidomide and
dexamethasone with or without daratumumab in subjects with relapsed or
refractory multiple myeloma previously treated with lenalidomide and a
proteasome inhibitor daratumumab/pomalidomide/dexamethasone vs
pomalidomide/dexamethasone (EMN14). NCT03180736. Available at: https://clinicaltrials.gov/ct2/show/NCT03180736
Last accessed May 2019.

¹³ ClinicalTrials.gov. Study of carfilzomib, daratumumab and
dexamethasone for patients with relapsed and/or refractory multiple
myeloma (CANDOR). NCT03158688. Available at: https://clinicaltrials.gov/ct2/show/NCT03158688
Last accessed May 2019.

¹⁴ ClinicalTrials.gov. A study to evaluate 3 dose schedules
of daratumumab in participants with smoldering multiple myeloma.
NCT02316106. Available at: https://clinicaltrials.gov/ct2/show/NCT02316106
Last accessed May 2019.

¹⁵ ClinicalTrials.gov. An efficacy and safety proof of
concept study of daratumumab in relapsed/refractory mantle cell
lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma.
NCT02413489. Available at: https://clinicaltrials.gov/ct2/show/NCT02413489
Last accessed May 2019.

¹⁶ Johnson & Johnson. Janssen Biotech announces global
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daratumumab. Press release August 30, 2012. Available at: https://www.jnj.com/media-center/press-releases/janssen-biotech-announces-global-license-and-development-agreement-for-investigational-anti-cancer-agent-daratumumab
Last accessed May 2019.

¹⁷ American Society of Clinical Oncology. Multiple myeloma:
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¹⁹ De Angelis R, Minicozzi P, Sant M, et al. Survival
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Europe 2000-2007: results of EUROCARE-5 population-based study. Eur J
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²⁰ Abdi J, Chen G, Chang H, et al. Drug resistance in
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²¹ National Cancer Institute. NCI dictionary of cancer terms:
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²² Richardson P, Mitsiades C, Schlossman R, et al. The
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Soc Hematol Educ Program. 2007:317-23.

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June 2019

CP-94166

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