Bli medlem
Bli medlem

Du är här

2015-04-15

Novartis International AG: Data in The Lancet show Novartis drug Arzerra® plus chlorambucil improved median progression-free survival by 71% in CLL patients

Novartis International AG / Data in The Lancet show Novartis drug Arzerra®
plus chlorambucil improved medianprogression-free survival by 71% in CLL
patients . Processed and transmitted by NASDAQ OMX Corporate Solutions.The
issuer is solely responsible for the content of this announcement.
* Significant improvement in PFS seen with Arzerra plus chlorambucil in
previously untreated patients with CLL for whom fludarabine-based therapy
was inappropriate
* Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed adult
leukemia in Western countries, accounting for approximately 1 in 4 cases of
all leukemia[1],[2]
* 75% of CLL patients are over 65 years of age at time of diagnosis and
majority have at least one comorbidity such as hypertension, diabetes,
heart disease or COPD[3],[4],[5]

Basel, April 15, 2015
-
Phase III data published inThe Lancet
showed that treatment with Arzerra®(ofatumumab) plus chlorambucil, a
chemotherapy, resulted in a statistically significant improvement in
progression free survival (PFS) versus chlorambucil alone in treatment-naïve
patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based
therapy was considered inappropriate, mainly due to advanced age or the
presence of comorbidities.

CLL, the most commonly diagnosed adult leukemia in Western countries, accounts
for approximately 1 in 4 cases of all leukemia[1],[2]. The average age at the
time of diagnosis is approximately 71 years[2], and the majority of patients
with CLL have at least one comorbidity such as hypertension, diabetes, heart
disease or COPD[4],[5].

"Finding effective treatments with clinically acceptable safety profiles for
elderly patients with CLL and for those with co-existent chronic and
potentially life-threatening conditions continues to be a challenge," said
Prof. Peter Hillmen, St. James's University Hospital, Leeds, United Kingdom
and lead study author. "The results published in The Lancet reinforce our
understanding that the combination of ofatumumab plus chlorambucil provides
this patient population a treatment option that improves clinical health
outcomes in CLL."

The primary endpoint of the study was PFS according to the International
Workshop for Chronic Lymphocytic Leukaemia (iwCLL) updated 2008 National
Cancer Institute-sponsored Working Group (NCIWG) guidelines[6]. In this
clinical study, median PFS was improved by 71% in the group receiving
ofatumumab plus chlorambucil compared to the chlorambucil alone group (22.4
months vs 13.1 months, respectively; HR 0.57 [95% CI 0.45, 0.72]; p<0.0001).
Improvement in PFS was observed in most subgroups irrespective of age,
gender, disease stage and prognostic factors. More patients in the group
receiving ofatumumab plus chlorambucil (50%) experienced adverse events (AEs)
of grade 3 or greater compared to chlorambucil alone (43%), with neutropenia
being the most common adverse event (26% vs. 14%). Grade 3/4 infusion-related
reactions (IRRs) were reported in 10% of patients receiving ofatumumab plus
chlorambucil leading to drug withdrawal in 3% of patients and hospitalization
in 2% of patients. No fatal IRRs were reported.

"The results presented inThe Lancet
demonstrate that the addition of Arzerra to chlorambucil resulted in a
significant improvement in progression free survival, with an acceptable
safety profile," said Alessandro Riva, M.D., Global Head, Novartis Oncology
Development and Medical Affairs. "We are excited that Arzerra is now part of
the Novartis Oncology portfolio of products, and look forward to building
upon the body of evidence that supports the clinical benefit of Arzerra for
appropriate patients with CLL."

These Phase III data formed the basis for regulatory approvals in the United
States (US) and European Union (EU) in 2014, as well as the recent inclusion
of Arzerra plus chlorambucil in the National Comprehensive Cancer Network
(NCCN) treatment guidelines.

About the Study

This prospective, randomized, open-label, Phase III study (COMPLEMENT 1,
NCT00748189) included 447 patients with previously untreated CLL for whom
fludarabine-based therapy was considered inappropriate. Patients in the
study were randomized 1:1 to treatment with up to twelve cycles of ofatumumab
in combination with chlorambucil or up to twelve cycles of chlorambucil
alone.

The primary endpoint of the study was PFS according to the iwCLL updated 2008
NCIWG guidelines[6], using a blinded independent endpoints review committee.
Secondary endpoints included overall survival (OS), time to progression,
overall response rate (ORR), complete response (CR) rate, time to response,
duration of response, time to next therapy (TTNT), safety assessments,
pharmacokinetics, pharmacogenetics, and quality of life.

Findings from the study showed a 71% improvement in median PFS in the group
receiving ofatumumab plus chlorambucil compared to the group receiving
chlorambucil alone (22.4 months vs 13.1 months, respectively; HR 0.57 [95% CI
0.45, 0.72]; p<0.0001). Patients in the group receiving ofatumumab plus
chlorambucil [n=221] showed similar improvements in PFS across age groups
compared to the chlorambucil alone [n=226]. Improvement in PFS was observed
in most subgroups irrespective of age, gender, disease stage and prognostic
factors.

Additionally, patients in the combination arm also experienced significantly
longer TTNT when compared to chlorambucil alone (39.8 months vs 24.7 months,
respectively; HR 0.49 [95% CI: 0.36, 0.67]; p<0.0001). Patients in the
combination arm had a higher ORR (82% of patients vs 69% of patients,
respectively; odds ratio 2.16 [95% CI: 1.36-3.42]; p=0.001), with a better CR
rate (14% of patients vs 1% of patients, respectively). Compared to those on
chlorambucil alone, patients in the combination arm had a duration of
response of 22.1 months versus 13.2 months (HR 0.56 [95% CI: 0.43, 0.74];
p<0.001).

More patients in the group receiving Arzerra plus chlorambucil (combination)
experienced AEs of grade 3 or greater (50%) compared to chlorambucil alone
(43%). The most common AEs (>=2%) reported were neutropenia,
thrombocytopenia, anemia, infections, and infusion-related reactions.
Overall, AEs leading to treatment withdrawal were similar in both groups (13%
vs 13%). AE frequency with Arzerra plus chlorambucil was similar for older
patient groups (>=65 years old) compared with chlorambucil alone. Neutropenia
occurred more frequently in the combination group, but did not result in a
higher rate of infection, and thrombocytopenia and anemia were more
frequently observed in the chlorambucil alone group. The most common
infections were respiratory tract infections (27% for combination vs 31% for
chlorambucil alone) and there were similar frequencies of sepsis (3% vs 2%)
and opportunistic infections (4% vs 5%) reported in the combination and
chlorambucil alone groups, respectively.

Grade 3/4 IRRs were reported in 10% of patients receiving Arzerra plus
chlorambucil leading to drug withdrawal in 3% of patients and hospitalization
in 2% of patients. No fatal IRRs were reported. Deaths during treatment or
within 60 days after the last dose were similar in both groups (3% vs 3%).

About Arzerra

Arzerra (ofatumumab) is a human monoclonal antibody that is designed to target
the CD20 molecule found on the surface of chronic lymphocytic leukemia (CLL)
cells and normal B lymphocytes.

In the United States, Arzerra is approved for use in combination with
chlorambucil for the treatment of previously untreated patients with CLL for
whom fludarabine-based therapy is considered inappropriate. In the European
Union, Arzerra is approved for use in combination with chlorambucil or
bendamustine for the treatment of patients with CLL who have not received
prior therapy and who are not eligible for fludarabine-based therapy. Arzerra
is also approved for first-line use in Russia, Iceland, Norway, Luxembourg
and Brazil.

In more than 50 countries worldwide, Arzerra is also indicated as monotherapy
for the treatment of patients with CLL refractory to fludarabine and
alemtuzumab.

Arzerra is marketed under a co-development and collaboration agreement between
Genmab and Novartis, as successor in interest to GSK.

Important Safety Information for Arzerra (ofatumumab)

Treatment with Arzerra may cause side effects, some of which are serious and
life-threatening.

Treatment with Arzerra may cause a side effect called an infusion reaction,
which may be serious and possibly life-threatening. Before treatment with
Arzerra, doctors will prescribe 3 types of medicine to their patients to help
reduce the risk of an infusion reaction including, a steroid (to reduce
swelling and other symptoms of inflammation), a pain reliever, and an
antihistamine (to reduce allergic reactions). Even though patients receive
these medicines, they may still have an infusion reaction. If an infusion
reaction occurs, the doctor will stop their patient's treatment with Arzerra
so the infusion reaction can be treated. Patients should tell their doctor
or seek medical treatment right away if they have any of these symptoms while
receiving Arzerra or within 24 hours after receiving Arzerra: fever, chills,
rash, hives, chest pain, back pain, stomach pain, swelling, dizziness,
blurred vision, drowsiness, headache, cough, wheezing, or trouble breathing.

Treatment with Arzerra may cause hepatitis B virus (HBV) infection to reoccur,
which may cause serious liver problems and death. Patients should tell their
doctor if they have had HBV infection or are a carrier of HBV. Before
starting Arzerra, doctors will do a blood test to check for HBV infection. In
some patients, additional blood tests may be done during and several months
after treatment. Patients should call their doctor right away if they feel
more tired than usual or notice a yellowing of the skin or eyes. These may be
symptoms of hepatitis.

Progressive multifocal leukoencephalopathy (PML) is a rare brain infection
that can occur with treatment with Arzerra. PML causes severe disability and
can lead to death. Patients should call their doctor right away if they
notice new medical problems or problems that are getting worse, such as
confusion, dizziness or loss of balance, difficulty talking or walking, or
strength, vision or other problems that have lasted over several days.

Tumor lysis syndrome (TLS) can occur with treatment with Arzerra. TLS is
caused by the fast breakdown of cancer cells, which then release their
contents into the blood. This may lead to serious problems, including kidney
failure or an abnormal heartbeat. Doctors may do a blood test to check their
patients for TLS and may give medicines before starting treatment with
Arzerra to help prevent TLS.

Treatment with Arzerra can increase patients' chances for getting infections.
Some infections, such as ...

Författare Hugin

Tala om vad ni tycker

Tala om vad ni tycker

Ni är just nu inne på en betaversion av nya aktiespararna. Lämna gärna feedback på vad ni tycker i formuläret nedan.