Janssen Seeks Expanded Use of DARZALEX®▼ (daratumumab) Combination Therapy for Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma

First DARZALEX combination regimen being pursued as frontline
treatment option for transplant eligible patients with multiple myeloma

BEERSE, Belgium–(BUSINESS WIRE)–The Janssen Pharmaceutical Companies of Johnson & Johnson today
announced the submission of a Type II variation application to the
European Medicines Agency (EMA) for DARZALEX^®▼ (daratumumab)
in combination with bortezomib, thalidomide and dexamethasone (VTd) for
newly diagnosed patients with multiple myeloma who are eligible for
autologous stem cell transplant (ASCT).

The submission is supported by data from the Phase 3 CASSIOPEIA
(MMY3006) study. Additional information about this study can be found at www.ClinicalTrials.gov
(NCT02541383).

“With this regulatory submission, Janssen could help redefine treatment
for transplant eligible patients by providing the opportunity to be
treated with a daratumumab regimen for the very first time,” said José
Antonio Burón Vidal, Vice President, Medical Affairs, Europe, Middle
East and Africa (EMEA), Janssen-Cilag, S.A. “We continue to deliver
advances in multiple myeloma, and if approved, this could offer a
broader range of frontline patients a new treatment option and improved
outcomes.”

Janssen has also submitted
an application to the U.S. Food and Drug Administration (FDA) seeking
approval of daratumumab-VTd for newly diagnosed patients with multiple
myeloma who are eligible for autologous stem cell transplant (ASCT).

In Europe, daratumumab is indicated:¹

• 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 Trial²

The randomised, open-label, two-arm, multicentre, Phase 3 study is
sponsored by the French Intergroupe Francophone du Myelome (IFM) in
collaboration with the Dutch-Belgian Cooperative Trial Group for
Hematology Oncology (HOVON) and Janssen R&D, LLC. The study includes
participants with previously untreated multiple myeloma eligible for
high dose chemotherapy and ASCT. In the first part of the study, on
which the filing is based, participants were randomised to receive
either induction (before transplantation) and consolidation (after
transplantation) treatment with daratumumab combined with bortezomib,
thalidomide and dexamethasone or bortezomib, thalidomide and
dexamethasone alone. The primary endpoint is the proportion of patients
that achieve a stringent Complete Response (sCR) rate after
consolidation therapy. In the second part of the study, patients that
achieved a response will undergo a second randomisation to either
receive maintenance treatment of daratumumab or no further treatment
(observation). The primary endpoint of this part of the study is
progression free survival (PFS). The total duration for each participant
in the study will be approximately 138 weeks. The end of the study will
occur approximately five years after the last participant is randomised
in the second phase of the study. Disease assessments will be performed
every four weeks in the first phase of the study and then every eight
weeks in the second phase of the study.

About daratumumab

Daratumumab is a first-in-class³ biologic targeting CD38, a
surface protein that is highly expressed across multiple myeloma cells,
regardless of disease stage.⁴ 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.¹ A subset of myeloid derived suppressor cells (CD38+
MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were
decreased by daratumumab.¹ 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.^{2,5,6,7,8,9,10,11} 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.^12,13 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.¹⁴

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.¹⁵ In Europe, more than 48,200 people were diagnosed
with MM in 2018, and more than 30,800 patients died.¹⁶ Almost
40 percent of patients with MM do not reach five-year survival.¹⁷

Although treatment may result in remission, unfortunately, patients will
most likely relapse as there is currently no cure.¹⁸
Refractory MM is when a patient’s disease progresses within 60 days of
their last therapy.^19,20 Relapsed cancer is when the disease
has returned after a period of initial, partial or complete remission.²¹
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.²² Patients
who relapse after treatment with standard therapies, including
proteasome inhibitors and immunomodulatory agents, have poor prognoses
and few treatment options available.²³

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 R&D, LLC, Janssen Biotech, Inc. and
Janssen-Cilag S.A. 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
a recommendation to broaden the existing marketing authorisation
for daratumumab. 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 R&D, LLC, Janssen Biotech, Inc., Janssen-Cilag
S.A., the 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. None of the Janssen Pharmaceutical
Companies nor Johnson & Johnson undertakes to update any forward-looking
statement as a result of new information or future events or
developments.

References

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Last accessed March 2019.
² 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 March 2019.
³ Sanchez L, et al.
Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment
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10.1186/s13045-016-0283-0.
⁴ Fedele G, di Girolamo M,
Recine U, et al. CD38 ligation in peripheral blood mononuclear cells of
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Last accessed March 2019.
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¹¹ ClinicalTrials.gov. Study
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Last accessed March 2019.
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CP-81253
March 2019

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