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

Application supported by the Phase 3 MAIA study for daratumumab in
combination with lenalidomide and dexamethasone for the treatment of
patients newly diagnosed with multiple myeloma who are ineligible for
autologous stem cell transplant

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 lenalidomide and dexamethasone (Rd) for the
treatment of patients newly diagnosed with multiple myeloma who are
ineligible for autologous stem cell transplant (ASCT).

“Today’s submission brings us one step closer to our goal of improving
treatment outcomes for people newly diagnosed with multiple myeloma,”
said José Antonio Burón Vidal, VP Medical Affairs, Europe, Middle East
and Africa (EMEA), Janssen-Cilag Limited. “We are incredibly grateful to
the patients and investigators who participated in the MAIA clinical
trial programme and look forward to working closely with the regulatory
authorities to secure approval of this new combination.”

The submission is supported by data from the Phase 3 MAIA (MMY3008)
study, which were presented
at the 60th Annual Meeting of the American Society of Hematology.¹
The study showed that at a median follow-up of 28 months, daratumumab-Rd
significantly reduced the risk of disease progression or death by 44
percent in patients with newly diagnosed multiple myeloma who are
transplant ineligible compared to treatment with Rd alone (Hazard Ratio
[HR] = 0.56; 95 percent confidence interval [CI]: 0.43-0.73; p<0.0001).¹
The median progression-free survival (PFS) for daratumumab-Rd has
not yet been reached, compared to 31.9 months for patients who received
Rd alone.¹ The addition of daratumumab resulted in deeper
responses compared to Rd alone, including increased rates of complete
response (CR) or better (48 percent vs. 25 percent) and improved rates
of very good partial response (VGPR) or better (79 percent vs. 53
percent).¹ Within the study, patient health, functional
capacity, symptoms, psychosocial well-being, and life satisfaction were
evaluated through measures to assess change in health-related quality of
life by the European Organisation for Research and Treatment of Cancer
Quality of Life Questionnaire (EORTC QLQ-C30) and Euro Quality of Life
(EQ-5D-5L) Health State Profile Utility Score.²

The most common Grade 3/4 treatment-emergent adverse events (TEAEs) for
daratumumab-Rd (≥10 percent) included neutropenia (50 percent),
lymphopenia (15 percent), pneumonia (14 percent) and anaemia (12
percent).¹ Infusion-related reactions (IRRs) occurred in 41
percent of patients receiving daratumumab-Rd, 3 percent of which were
Grade 3/4.¹ Incidence of invasive second primary malignancy
was 3 percent in the daratumumab-Rd arm compared to 4 percent with Rd
alone.¹ TEAEs with an outcome of death were 7 percent in the
daratumumab-Rd arm compared to 6 percent in the Rd arm.¹ The
safety profile of daratumumab was consistent with that of previous
studies.^1,3,4,5,6,7

Daratumumab-Rd is being reviewed
by the U.S. Food and Drug Administration (FDA) under the Real-Time
Oncology Review (RTOR) pilot programme.

In Europe, daratumumab is indicated:⁸

• 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.

#ENDS#

About the MAIA Trial²
The randomised,
open-label, multicentre Phase 3 study included 737 newly diagnosed
patients with multiple myeloma ineligible for high-dose chemotherapy and
ASCT aged 45-90 years old (median age of 73 years). Patients were
randomised to receive either daratumumab-Rd or Rd alone in 28-day
Cycles. In the daratumumab-Rd treatment arm, patients received
daratumumab 16 (mg/kg) IV weekly for Cycles 1 – 2, every two weeks for
Cycles 3 – 6 and every 4 weeks for Cycle 7 and thereafter. Patients in
the daratumumab-Rd and Rd treatment arm received 25 mg of lenalidomide
on Days 1 – 21 of each 28-day Cycle, and dexamethasone at 40 mg once a
week for each Cycle. Patients in both treatment arms continued until
disease progression or unacceptable toxicity.

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.^9,10 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.¹¹ A subset of myeloid derived suppressor cells (CD38+
MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were
decreased by daratumumab.¹¹ 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.^{2,12,13,14,15,16,17,18} 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.^19,20 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.²¹

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.²² In Europe, more
than 48,200 people were diagnosed with MM in 2018, and more than 30,800
patients died.²³ Up to half of newly diagnosed patients do
not reach five-year survival,²⁴ and almost 29% of patients
with MM will die within one year of diagnosis.²⁵

Although treatment may result in remission, unfortunately, patients will
most likely relapse as there is currently no cure.²⁶
Refractory MM is when a patient’s disease progresses within 60 days of
their last therapy.^27,28 Relapsed cancer is when the disease
has returned after a period of initial, partial or complete remission.²⁹
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.³⁰ Patients
who relapse after treatment with standard therapies, including
proteasome inhibitors and immunomodulatory agents, have poor prognoses
and few treatment options available.³¹

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 International
NV, and Janssen-Cilag Limited 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-Cilag International NV,
Janssen-Cilag Limited, Janssen Biotech, Inc., any of the Janssen
Pharmaceutical Companies of Johnson & Johnson 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,” in the
company’s most recently filed Quarterly Report on Form 10-Q and in 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.

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CP-81255
March 2019

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