Bli medlem
Bli medlem

Du är här

2018-09-13

AstraZeneca: US FDA approves Lumoxiti (moxetumomab pasudotox-tdfk) for certain patients with relapsed or refractory hairy c...

Approval of Lumoxiti, a first-in-class medicine for hairy cell
leukaemia marks first new treatment option for patients in over 20
years1

75% of patients receiving Lumoxiti achieved an overall response; 30%
had a durable complete response2

AstraZeneca and MedImmune, its global biologics research and
development arm, announced today that the US Food and Drug
Administration (FDA) has approved Lumoxiti (moxetumomab
pasudotox-tdfk) for the treatment of adult patients with relapsed or
refractory hairy cell leukaemia (HCL) who have received at least two
prior systemic therapies, including treatment with a purine
nucleoside analog. Lumoxiti is not recommended in patients with
severe renal impairment (CrCl ? 29 mL/min).2 The Phase III trial
results demonstrated 75% (95% confidence interval [CI]: 64, 84) of
patients receiving Lumoxiti achieved an overall response; 30% (95%
CI: 20, 41) had a durable complete response.2,3

Dave Fredrickson, Executive Vice-President, Global Head Oncology
Business Unit, said: "Today's FDA approval of Lumoxiti represents a
significant milestone for people living with hairy cell leukaemia, a
rare blood cancer that can result in serious and life-threatening
conditions. For patients, this approval provides the first
FDA-approved medicine for this condition in more than 20 years."

Robert J. Kreitman, MD, Senior Investigator, Head of Clinical
Immunotherapy Section, Laboratory of Molecular Biology, Center for
Cancer Research, National Cancer Institute, and Principal
Investigator of the Phase III clinical trial, said: "While many
patients with hairy cell leukaemia experience a remission with
current treatments, 30% to 40% will relapse five to ten years after
their first treatment.4 With subsequent treatments, durations of
response diminish and toxicities accumulate, and few approved
treatment options exist.5,6 Moxetumomab pasudotox represents a
promising non-chemotherapeutic agent for HCL, addressing an unmet
medical need for physicians and their patients."

Lumoxiti was approved under FDA Priority Review.7 The approval is
based on data from the Phase III single-arm, open-label `1053' trial
of Lumoxiti monotherapy in 80 patients who have received at least two
prior therapies, including a purine nucleoside analog.3 The primary
endpoint of the trial was durable complete response.3 Summary of key
results from the trial, as determined by a blinded independent
central review:2

+---------------------------------+------------------+
|Efficacy measure |Result %, (95% CI)|
+---------------------------------+------------------+
|Durable complete response ratea,b|30% (20, 41) |
+---------------------------------+------------------+
|Overall response ratec |75% (64, 84) |
+---------------------------------+------------------+
|Complete response rated |41% (30, 53) |
+---------------------------------+------------------+
|Partial response ratee |34% (24, 45) |
+---------------------------------+------------------+
|Haematologic remission rateb |80% |
+---------------------------------+------------------+

a Durable complete response is defined as patients who achieved
complete response with haematologic remission for a duration of more
than 180 days

b Haematologic remission is defined as haemoglobin > 11g/dL,
neutrophils > 1500/mm3, platelets > 100,000/mm3 without transfusions
or growth factor for at least 4 weeks

c Overall response rate is defined as best overall response of
complete response or partial response

d Complete response is defined as clearing of the bone marrow of hairy
cells by routine haematoxylin and eosin stain, radiologic resolution
of pre-existing lymphadenopathy and/or organomegaly, and haematologic
remission

e Partial response is defined as ? 50% decrease or normalisation (<
500/mm3) in peripheral blood lymphocyte count, reduction of
pre-existing lymphadenopathy and/or organomegaly, and haematologic
remission

The median time to haematologic remission was 1.1 months (range: 0.2
to 13).2 At data cut-off, the median duration of complete response
was not yet reached after a median 16.7 months of follow-up.2

Capillary leak syndrome (CLS) and haemolytic uraemic syndrome (HUS),
including life-threatening cases of each, have been reported among
patients treated with Lumoxiti. In the combined safety database of
129 HCL patients treated with Lumoxiti, Grade 3 or 4 CLS occurred in
1.6% and 2% of patients, respectively. Grade 3 or 4 HUS occurred in
3% and 0.8% of patients, respectively.2

In the `1053' trial of 80 patients, the most common Grade 3 or 4
adverse reactions (reported in at least ? 5% of patients) were
hypertension, febrile neutropenia, and HUS. HUS was the most common
adverse reaction leading to discontinuation (5%). The most common
adverse reactions (? 20%) of any grade were infusion related
reactions (50%), oedema (39%), nausea (35%), fatigue (34%), headache
(33%), pyrexia (31%), constipation (23%), anaemia (21%), and
diarrhoea (21%). The most common laboratory abnormalities (? 20%) of
any grade were creatinine increased, ALT increased, hypoalbuminaemia,
AST increased, hypocalcaemia, hypophosphataemia, haemoglobin
decreased, neutrophil count decreased, hyponatreamia, blood bilirubin
increased, hypokalaemia, GGT increased, hypomagnesaemia, platelet
count decreased, hyperuricaemia, and alkaline phosphate increased.2

The recommended dose of Lumoxiti is 0.04 mg/kg administered as an
intravenous infusion over 30 minutes on days 1, 3, and 5 of each
28-day cycle up to 6 cycles, disease progression, or unacceptable
toxicity.2

About hairy cell leukaemia

Hairy cell leukaemia (HCL) is a rare, chronic, and slow-growing
leukaemia in which the bone marrow overproduces abnormal B cell
lymphocytes.8,9 HCL can result in serious and life-threatening
conditions, including infections, bleeding and anaemia.10
Approximately 1,000 people are diagnosed with HCL in the US each
year.11 While many patients initially respond to treatment, 30% to
40% will relapse five to ten years after their first treatment.4 With
no established standard of care and very few treatments available,
there remains significant unmet medical need for people with relapsed
or refractory HCL.4,8

About Lumoxiti

Lumoxiti (moxetumomab pasudotox, formerly CAT8015 or HA22) is a
CD22-directed cytotoxin and a first-in-class treatment in the US for
adult patients with relapsed or refractory hairy cell leukaemia (HCL)
who have received at least two prior systemic therapies, including
treatment with a purine nucleoside analog. Lumoxiti is not
recommended in patients with severe renal impairment (CrCl ? 29
mL/min).2 It comprises the CD22 binding portion of an antibody fused
to a truncated bacterial toxin; the toxin inhibits protein synthesis
and ultimately triggers apoptotic cell death.2 Lumoxiti has been
granted Orphan Drug Designation by the FDA for the treatment of HCL.

About the `1053' Phase III trial

The `1053' trial is a single-arm, multicentre Phase III clinical trial
assessing the efficacy, safety, immunogenicity and pharmacokinetics
of moxetumomab pasudotox monotherapy in patients with relapsed or
refractory HCL who have received at least two prior therapies,
including one purine nucleoside analog. The trial was conducted in 80
patients across 34 sites in 14 countries. The primary endpoint was
durable complete response (CR), defined as CR with haematologic
remission (blood count normalisation) for >180 days. Secondary
outcome measures included overall response rate, relapse free
survival, progression-free survival, time to response, safety,
pharmacokinetic and immunogenic potential.7

Early discovery of moxetumomab pasudotox was led by the National
Cancer Institute (NCI). The collaboration between NCI and MedImmune,
AstraZeneca's global biologics research and development arm, is an
example of how scientific partnerships can lead to important advances
for cancer patients.

About AstraZeneca in Haematology

Leveraging its strength in oncology, AstraZeneca has established
haematology as one of four key oncology disease areas of focus and is
accelerating development of a broad portfolio of potential blood
cancer treatments. AstraZeneca and Acerta Pharma, its haematology
research and development centre of excellence, received US FDA
approval for the first medicine in this franchise, Calquence
(acalabrutinib)
(https://www.astrazeneca.com/media-centre/press-releases/2017/us-fda-appr...),
in October 2017.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly-growing portfolio of new medicines that has the potential to
transform patients' lives and the Company's future. With at least six
new medicines to be launched between 2014 and 2020, and a broad
pipeline of small molecules and biologics in development, we are
committed to advance Oncology as a growth driver for AstraZeneca
focused on lung, ovarian, breast and blood cancers. In addition to
our core capabilities, we actively pursue innovative partnerships and
investments that accelerate the delivery of our strategy, as
illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development of
personalised combinations, AstraZeneca has the vision to redefine
cancer treatment and one day eliminate cancer as a cause of death.

About MedImmune

MedImmune is the global biologics research and development arm of
AstraZeneca, a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialisation of
small molecule and biologic prescription medicines. MedImmune is
pioneering innovative research and exploring novel pathways across
Oncology, Respiratory, Cardiovascular, Renal & Metabolic Diseases,
and Infection and Vaccines. The MedImmune headquarters is located in
Gaithersburg, MD, one of AstraZeneca's three global R&D centres, with
additional sites in Cambridge, UK and South San Francisco, CA. For
more information, please visit www.medimmune.com
(http://s.bl-1.com/h/ch6zqQpo?url=https://www.medimmune.com/).

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal & Metabolism
and Respiratory. AstraZeneca operates in over 100 countries and its

Författare Cision

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.