DUBLIN, Dec. 3, 2020 /PRNewswire/ -- Jazz Pharmaceuticals
plc (Nasdaq: JAZZ), along with its partner, PharmaMar (MSE: PHM),
today announce results from the ATLANTIS Phase 3 multicenter,
randomized, controlled study evaluating Zepzelca™ (lurbinectedin)
in combination with doxorubicin versus physician's choice of
topotecan or cyclophosphamide/doxorubicin/vincristine (CAV) for
adult patients with small cell lung cancer (SCLC) whose disease
progressed following one prior platinum-containing line. Patients
received lurbinectedin at 2.0mg/m2 in the combination
arm, which is lower than the FDA approved dose of Zepzelca
at 3.2mg/m2.
The study did not meet the pre-specified criteria of
significance for the primary endpoint of overall survival (OS) in
the intent-to-treat (ITT) population comparing lurbinectedin in
combination with doxorubicin to the control arm, though there was
no adverse effect on OS with the experimental arm. Based on the
study design, no additional hypotheses were formally tested.
Importantly, key secondary and subgroup analyses favored the
lurbinectedin combination arm. Lurbinectedin monotherapy was not
tested in ATLANTIS.
The safety data in this study was consistent with the known
safety profile of lurbinectedin monotherapy with no new safety
signals observed. The experimental arm showed favorable safety and
tolerability with regard to Grade-3 or greater drug related adverse
events (AEs), deaths due to AEs, hematologic toxicity, dose
reductions and treatment discontinuations due to AEs, compared to
the control arm.
"Bringing Zepzelca to the U.S. market earlier this year
alongside our partner, PharmaMar, was an important advance for
adults with metastatic SCLC, an aggressive disease with a
historically poor prognosis," said Robert
Iannone M.D., M.S.C.E., executive vice president, research
and development of Jazz Pharmaceuticals. "While the
combination of lurbinectedin and doxorubicin did not achieve the
primary endpoint in this study, the overall results support the
activity and tolerability of lurbinectedin in this line of therapy.
We look forward to the further development of lurbinectedin in SCLC
and other tumors, both as monotherapy and in combination."
"We remain committed to improving outcomes for patients with
metastatic small cell lung cancer where there is a high unmet
medical need; we continue to evaluate the safety and efficacy of
lurbinectedin in SCLC and other tumors. The drug's activity in this
disease and setting has been reinforced in this trial," said
Luis Mora, managing director,
oncology business unit, PharmaMar. "We extend our gratitude to the
patients, physicians and their staff as well as caregivers who
participated in this clinical study."
"Historically, patients with relapsed SCLC often face difficult
odds due to the aggressive nature of the disease and they have had
very limited treatment options. As a physician treating patients
with SCLC, I'm confident in lurbinectedin as an effective new
option in this traditionally challenging therapeutic area,"
Alberto Chiappori, MD, senior member
of oncology and medicine for the Department of Thoracic Oncology at
the H. Lee Moffitt Cancer Center and Research Institute and
ATLANTIS Phase 3 study investigator.
Results will be discussed with the appropriate regulatory
authorities and will be presented at a future medical meeting.
The U.S. Food and Drug Administration (FDA) approved
Zepzelca under accelerated approval in June 2020 for the treatment of adult patients
with metastatic SCLC with disease progression on or after
platinum-based chemotherapy. The approval is based on ORR and
duration of response demonstrated in an open-label, monotherapy
clinical study. The companies will provide the ATLANTIS data to FDA
and look forward to working with the agency to determine the
confirmatory data that is needed for full approval.
ATLANTIS Phase 3 Study Design
The ATLANTIS Phase 3
study enrolled 613 patients at 154 sites primarily in the U.S.,
Canada, Latin America and Western Europe from September 2016 through July 2018. Patients enrolled were ≥18 years with
histologically or cytologically confirmed diagnosis of limited or
extensive stage SCLC, had failed one prior platinum-containing
regimen, and had a chemotherapy-free interval (CTFI, time from the
last dose of first-line chemotherapy to the occurrence of
progressive disease) ≥ 30 days. Patient inclusion criteria included
small-cell carcinoma of unknown primary site with or without
neuroendocrine features confirmed in histology test(s) performed on
metastatic lesion(s) are eligible, if Ki-67/MIB-1 is expressed in
>50 percent of tumor cells.
In the trial, patients were randomized in a 1:1 ratio to receive
lurbinectedin in combination with doxorubicin or physician's choice
of topotecan OR cyclophosphamide/doxor ubicin/vincristine (CAV).
The primary endpoint was overall survival. The secondary endpoints
were 1) the difference in OS for patients in
the lurbinectedin/doxorubicin arm compared to patients treated
with CAV; 2) OS and progression free survival (PFS) in patients
with or without CNS involvement; 3) PFS by independent review
committee (IRC); 4) antitumor activity defined by objective
response rate (ORR) per IRC; and 5) duration of response per
IRC.
The study sample was stratified by the following factors: CTFI
(chemotherapy free interval); ECOG performance status (0 vs. 1-2);
CNS involvement vs. no involvement; prior immunotherapy against
either programmed cell death protein-1 (PD-1) or programmed death
ligand-1 (PD-L1); and investigator preference of topotecan and
CAV.
About Zepzelca™ (lurbinectedin)
Zepzelca is an alkylating drug that binds guanine residues
within DNA. This triggers a cascade of events that can affect the
activity of DNA binding proteins, including some transcription
factors, and DNA repair pathways, resulting in disruption of the
cell cycle and eventual cell death.1
Zepzelca for injection 4 mg is a prescription
medicine used to treat adults with a kind of lung cancer called
small cell lung cancer that has spread to other parts of the body
(metastatic) and who have received treatment with chemotherapy that
contains platinum, and it did not work or is no longer
working. Zepzelca is approved based on response
rate and how long the response lasted. Additional studies will
further evaluate the benefit of Zepzelca for this
use.
Important Safety Information
Before receiving ZEPZELCA, tell your healthcare provider
about all of your medical conditions, including if you:
- have liver or kidney problems.
- are pregnant or plan to become pregnant. ZEPZELCA can harm your
unborn baby.
Females who are able to become pregnant:
-
- Your healthcare provider should do a pregnancy test before you
start treatment with ZEPZELCA.
- You should use effective birth control (contraception) during
treatment with and for 6 months after your final dose of
ZEPZELCA.
- Tell your healthcare provider right away if you become pregnant
or think that you are pregnant during treatment with ZEPZELCA.
Males with female partners who are able to become
pregnant should use effective birth control during
treatment with and for 4 months after your final dose of
ZEPZELCA.
- are breastfeeding or plan to breastfeed. It is not known if
ZEPZELCA passes into your breastmilk. Do not breastfeed during
treatment with ZEPZELCA and for 2 weeks after your final dose of
ZEPZELCA. Talk to your healthcare provider about the best way to
feed your baby during treatment with ZEPZELCA.
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. Certain other medicines may
affect how ZEPZELCA works.
What should I avoid while using ZEPZELCA?
Avoid eating or drinking grapefruit, or products that contain
grapefruit juice during treatment with ZEPZELCA.
ZEPZELCA can cause serious side effects, including:
- Low blood cell counts. Low blood counts including
low neutrophil counts (neutropenia) and low platelet counts
(thrombocytopenia) are common with ZEPZELCA, and can also be
severe. Some people with low white blood cell counts may get fever,
or an infection throughout the body (sepsis), that can cause death.
Your healthcare provider should do blood tests before you receive
each treatment with ZEPZELCA to check your blood cell counts.
Tell your healthcare provider right away if you
develop:
-
- fever or any other signs of infection
- unusual bruising or bleeding
- tiredness
- pale colored skin
- Liver problems. Increased liver function tests are
common with ZEPZELCA, and can also be severe. Your healthcare
provider should do blood tests to check your liver function before
you start and during treatment with ZEPZELCA.
Tell your healthcare provider right away if you develop symptoms
of liver problems including:
-
- loss of appetite
- nausea or vomiting
- pain on the right side of your stomach area (abdomen)
Your healthcare provider may temporarily stop treatment, lower
your dose, or permanently stop ZEPZELCA if you develop low blood
cell counts or liver problems during treatment with ZEPZELCA.
The most common side effects of ZEPZELCA include:
- tiredness
- low white and red blood cell counts
- increased kidney function blood test (creatinine)
- increased liver function blood tests
- increased blood sugar (glucose)
- nausea
- decreased appetite
- muscle and joint (musculoskeletal) pain
- low level of albumin in the blood
- constipation
- trouble breathing
- low levels of sodium and magnesium in the blood
- vomiting
- cough
- diarrhea
These are not all of the possible side effects of ZEPZELCA.
Call your doctor for medical advice about side effects. You
are encouraged to report negative side effects of prescription
drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088. You may also report side effects to Jazz
Pharmaceuticals at 1-800-520-5568.
More information about Zepzelca, including Full Prescribing
Information and Patient Information, is
available here.
ZEPZELCA is a trademark of PharmaMar, S.A. used by Jazz
Pharmaceuticals under license.
About Jazz Pharmaceuticals
Jazz
Pharmaceuticals plc (Nasdaq: JAZZ) is a global
biopharmaceutical company dedicated to developing and
commercializing life-changing medicines that transform the lives of
patients with serious diseases - often with limited or no options.
We have a diverse portfolio of marketed medicines and novel
product candidates, from early- to late-stage development, in key
therapeutic areas. Our focus is in neuroscience, including sleep
and movement disorders, and in oncology, including hematologic
malignancies and solid tumors. We actively explore new options for
patients including novel compounds, small molecule advancements,
biologics and innovative delivery technologies. Jazz is
headquartered in Dublin, Ireland and has employees around
the globe, serving patients in more than 90 countries. For more
information, please visit www.jazzpharmaceuticals.com and
follow @JazzPharma on Twitter.
About PharmaMar
Headquartered in Madrid, PharmaMar is a biopharmaceutical
company, focused on oncology and committed to research and
development which takes its inspiration from the sea to discover
molecules with antitumor activity. It is a company that seeks
innovative products to provide healthcare professionals with new
tools to treat cancer. Its commitment to patients and to research
has made it one of the world leaders in the discovery of antitumor
drugs of marine origin.
PharmaMar has a pipeline of drug candidates and a robust R&D
oncology program. It develops and commercializes Yondelis® in
Europe and has other
clinical-stage programs under development for several types of
solid cancers: lurbinectedin (PM1183), PM184 and PM14. With
subsidiaries in Germany,
Italy, France, Switzerland, Belgium, Austria and the
United States. PharmaMar wholly owns other companies:
GENOMICA, a molecular diagnostics company; Sylentis, dedicated to
researching therapeutic applications of gene silencing (RNAi). To
learn more about PharmaMar, please visit us at
www.pharmamar.com.
"Safe Harbor" Statement under the Private Securities
Litigation Reform Act of 1995
This press release contains
forward-looking statements, including, but not limited to,
statements related to engaging with the appropriate regulatory
agencies, including providing the ATLANTIS data to FDA
and working with the agency to determine the confirmatory data that
is needed for full approval of lurbinectedin; the further
development of lurbinectedin in SCLC and other tumors, both as
monotherapy and in combination; the company's belief that the
overall results of ATLANTIS support the activity and tolerability
of lurbinectedin in adults with metastatic SCLC; and
other statements that are not historical facts. These
forward-looking statements are based on Jazz
Pharmaceuticals' current plans, objectives, estimates,
expectations and intentions and inherently involve significant
risks and uncertainties. Actual results and the timing of events
could differ materially from those anticipated in such
forward-looking statements as a result of these risks and
uncertainties, which include, without limitation, risks and
uncertainties associated with pharmaceutical product development,
including clinical data read-outs; the time-consuming and uncertain
regulatory approval process, including the risk that FDA may not
grant full approval to lurbinectedin; and other risks and
uncertainties affecting Jazz Pharmaceuticals and its
development programs, including those described from time to time
under the caption "Risk Factors" and elsewhere in Jazz
Pharmaceuticals plc's Securities and Exchange
Commission filings and reports (Commission File No.
001-33500), including Jazz Pharmaceuticals' Quarterly
Report on Form 10-Q for the quarter ended September 30,
2020 and future filings and reports by Jazz
Pharmaceuticals. Other risks and uncertainties of which Jazz
Pharmaceuticals is not currently aware may also
affect Jazz Pharmaceuticals' forward-looking statements
and may cause actual results and the timing of events to differ
materially from those anticipated. The forward-looking statements
herein are made only as of the date hereof or as of the dates
indicated in the forward-looking statements, even if they are
subsequently made available by Jazz Pharmaceuticals on
its website or otherwise. Jazz Pharmaceuticals undertakes
no obligation to update or supplement any forward-looking
statements to reflect actual results, new information, future
events, changes in its expectations or other circumstances that
exist after the date as of which the forward-looking statements
were made.
References:
1. ZEPZELCA (lurbinectedin) Prescribing
Information. Palo Alto, CA: Jazz
Pharmaceuticals, Inc.
Jazz Pharmaceuticals Media and Investor Relations
Contact
Media Contact:
Jacqueline Kirby, Vice President, Corporate
Affairs & Government Relations
Ireland +353 1 697 2141 U.S. +1
215 867 4910
Investor Contact:
Kathee
Littrell, Vice President, Investor Relations
Ireland +353 1 634 7887 U.S. +1
650 496 2717
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