TIDMAZN
RNS Number : 7534A
AstraZeneca PLC
14 September 2018
14 September 2018 07:00 BST
US FDA approves Lumoxiti (moxetumomab pasudotox-tdfk)
for certain patients with relapsed or refractory hairy cell
leukaemia
Approval of Lumoxiti, a first-in-class medicine for hairy cell
leukaemia
marks first new treatment option for patients in over 20
years(1)
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 rate(a,b) 30% (20, 41)
-------------------
Overall response rate(c) 75% (64, 84)
-------------------
Complete response rate(d) 41% (30, 53)
-------------------
Partial response rate(e) 34% (24, 45)
-------------------
Haematologic remission rate(b) 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/mm(3) , platelets > 100,000/mm(3)
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/mm(3) ) 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), 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.
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 innovative medicines are used by millions of
patients worldwide.
For more information, please visit www.astrazeneca.com and
follow us on Twitter @AstraZeneca.
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AstraZeneca PLC
References
1. US Food and Drug Administration. Drugs@FDA: FDA Approved Drug
Products. Leustatin (cladribine). Available online. Accessed August
2018.
2. Lumoxiti (moxetumomab pasudotox-tdfk) Prescribing
Information. AstraZeneca Pharmaceuticals LP, Wilmington, DE.
2018.
3. ClinicalTrials.gov. Moxetumomab Pasudotox for Advanced Hairy
Cell Leukemia. Available Online. Accessed August 2018.
4. Lopez-Rubio M, Garcia-Marco JA. Current and emerging
treatment options for hairy cell leukemia. Onco Targets Ther.
2015;8:2147-2156. Available online. Accessed August 2018.
5. Zinzani PL, Pellegrini C, Stefoni V, et al. Hairy cell
leukemia: evaluation of the long-term outcome in 121 patients.
Cancer. 2010;116(20):4788-4792.
6. Kreitman RJ, Arons E. Update on Hairy Cell Leukemia Clinical
Advances in Hematology and Oncology 2018. Clin Adv Hematol Oncol.
2018;16(3):205-215. Available Online. Accessed August 2018.
7. US Food and Drug Administration. Priority Review. Available Online. Accessed August 2018.
8. National Institutes of Health. Hairy Cell Leukemia. Available Online. Accessed August 2018.
9. Hairy Cell Leukemia Foundation. Hairy cell leukemia. Available online. Accessed August 2018.
10. Hairy Cell Leukemia Foundation. Complications. Available
Online. Accessed August 2018.
11. Troussard X, Cornet E. Hairy cell leukemia 2018: Update on
diagnosis, risk--stratification, and treatment. Am J Hematol.
2017;92(12):1382-1390. Published online November 7, 2017. Available
Online. Accessed August 2018.
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