– Four-year follow-up analysis from the Phase
III CLL14 study showed progression-free survival rate of 74.0% in
previously untreated patients with chronic lymphocytic leukemia
(CLL) three years after completion of a one-year fixed-duration
treatment with Venclexta plus Gazyva –
– New Phase III MURANO study data suggested
certain genetic risk factors may help tailor treatments for
patients with previously treated CLL –
– A post-hoc analysis from the Phase III
VIALE-A study in newly diagnosed acute myeloid leukemia indicated
increased duration of response, event-free survival and overall
survival in patients who achieved undetectable minimal residual
disease –
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX:
RHHBY), today announced the latest data from three pivotal Phase
III studies of Venclexta® (venetoclax) – CLL14, MURANO and VIALE-A
– to be presented at the European Hematology Association Virtual
Congress, June 9-17 (EHA2021). Long-term follow-up data from the
CLL14 and MURANO studies support the primary analysis of Venclexta
in chronic lymphocytic leukemia (CLL) and the possibility of
tailoring treatment approaches based on genetic risk factors.
Furthermore, the latest research shows the potential of minimal
residual disease (MRD) as a key measure of disease response in CLL
and acute myeloid leukemia (AML).
“The data from these Venclexta combinations support our
continued commitment to provide valuable therapeutic options for
patients with hard-to-treat blood cancers,” said Levi Garraway,
M.D., Ph.D., chief medical officer and head of Global Product
Development. “These data also advance our understanding of minimal
residual disease, which we believe is a useful endpoint that may
help identify patients more quickly who are in need of additional
treatment.”
Four-Year Follow-Up Analysis of the Phase III CLL14
Study
This four-year post-hoc analysis of investigator-assessed
progression-free survival (PFS) had a median follow-up of 52.4
months (interquartile range: 49.5-56.2 months). The fixed treatment
duration (12 months) study indicated that the chemotherapy-free
Venclexta plus Gazyva® (obinutuzumab) regimen had an estimated PFS
rate of 74.0% vs 35.4% for Gazyva plus chlorambucil. Importantly,
the time to next treatment (TTNT) was significantly longer among
patients treated with the Venclexta plus Gazyva regimen versus the
comparator (four-year TTNT 81.1% vs 59.9%; HR 0.46, 95% CI
[0.32-0.65], p<0.0001). Abstract #S146, oral presentation.
Furthermore, 30 months after the end of treatment, 26.9% of the
Venclexta-treated patients still had undetectable MRD (uMRD)
compared with 3.2% of those treated with the comparator.
Undetectable MRD, sometimes referred to as MRD-negativity, means
that no cancer cells could be detected using a specific and highly
sensitive test, and is defined as less than one cancer cell in
10,000 leukocytes. Undetectable MRD is emerging as a measure of
disease response that may be useful to consider in treatment
decision-making.
Common grade 3-4 adverse events with Venclexta and Gazyva at 28
months follow-up were low white blood cell count and
infections.
Substudy from the Phase III MURANO Study
Results from this substudy suggested that increased prevalence
of certain unfavorable genetic risk factors negatively impacted the
MRD response of patients who were retreated with Venclexta plus
Rituxan® (rituximab) after progression on treatment with that
regimen. These data indicate the potential to tailor treatment
approaches for patients with previously treated CLL based on
genetic risk factors. Abstract #EP599, poster presentation.
Post-Hoc Analysis of the Phase III VIALE-A Study
Additionally, a post-hoc analysis from the Phase III VIALE-A
study suggested the value of continued research to understand the
role of MRD monitoring in AML. In the analysis, patients who
achieved a composite complete remission and uMRD following
treatment with Venclexta and azacitidine, a hypomethylating agent,
had improved survival outcomes compared with those who were
MRD-positive following treatment. The 12-month estimates for
duration of response, overall survival and event-free survival for
both groups are listed below:
Achieved composite complete
remission and uMRD
(MRD<10-3)
Did not achieve composite
complete remission and
uMRD (MRD≥10-3)
Duration of response
81.2% (95% CI 69.3-88.9)
46.6% (95% CI 35.6-56.8)
Overall survival
94.0% (95% CI 84.7-97.7)
67.9% (95% CI 57.6-76.2)
Event-free survival
83.2% (95% CI 71.6-90.3)
45.4% (95% CI 35.2-55.0)
Adverse events of grade ≥3 (MRD<10-3/MRD≥10-3) were febrile
neutropenia (50%/43%), neutropenia (50%/35%) and thrombocytopenia
(44%/44%), similar to the overall population. Abstract #S137, oral
presentation.
Genentech is collaborating with regulatory authorities and
others in the industry to advance understanding of MRD. The company
continues to investigate Venclexta in a robust clinical development
program, including in the Phase III CRISTALLO trial in previously
untreated CLL, which uses MRD as a primary endpoint.
Venclexta is approved in the United States and European Union in
combination with Rituxan for the treatment of adult patients with
CLL who have received at least one prior therapy; in combination
with Gazyva for the treatment of adult patients with previously
untreated CLL; and as a monotherapy for the treatment of CLL in the
presence of 17p deletion or TP53 mutation in people who are
unsuitable for or have failed a B-cell receptor pathway
inhibitor.
Venclexta is also approved in the United States in combination
with azacitidine, decitabine or low dose cytarabine for the
treatment of newly diagnosed AML in adults 75 years or older, or
who have comorbidities that preclude use of intensive induction
chemotherapy. In the European Union, Venclexta is approved in
combination with a hypomethylating agent for the treatment of adult
patients with newly diagnosed AML who are ineligible for intensive
chemotherapy.
About the CLL14 Study
CLL14 [NCT02242942] is a randomized Phase III study evaluating
the combination of fixed-duration Venclexta® (venetoclax) plus
Gazyva® (obinutuzumab) compared to Gazyva plus chlorambucil in
adult patients with previously untreated chronic lymphocytic
leukemia (CLL) and co-existing medical conditions. 432 patients
with previously untreated CLL were randomly assigned to receive
either a 12-month duration of Venclexta alongside six-month
duration of Gazyva (Arm A) or six-month duration of Gazyva
alongside 12-month duration of chlorambucil (Arm B). Arm A started
with an initial dosing of Gazyva followed by a five-week Venclexta
dose ramp-up to help reduce the risk of tumor burden. The primary
endpoint of the study is investigator-assessed progression-free
survival (PFS). Secondary endpoints included PFS assessed by
independent review committee, minimal residual disease (MRD)
status, overall response rate, complete response rate, and safety.
The CLL14 study is being conducted in cooperation with the German
CLL Study Group, headed by Michael Hallek, M.D., University of
Cologne.
About the MURANO Study
MURANO [NCT02005471] is a Phase III open-label, international,
multicenter, randomized study evaluating the efficacy and safety of
fixed-duration Venclexta (venetoclax) in combination with Rituxan®
(rituximab) compared to bendamustine in combination with Rituxan
(BR). All treatments were of fixed duration. Following a five-week
dose ramp-up schedule for Venclexta patients on the Venclexta plus
Rituxan arm received six cycles of Venclexta plus Rituxan followed
by Venclexta monotherapy for up to two years total. The study
included 389 patients with chronic lymphocytic leukemia (CLL), with
or without 17p deletion, who had been previously treated with at
least one line of therapy. A substudy from 2018 onward enrolled 34
relapsed or refractory CLL patients who progressed after initial
treatment to receive Venclexta plus Rituxan as retreatment (n=25)
or who crossed-over from the BR arm (n=9). The primary endpoint of
the study was progression-free survival. Secondary endpoints
included overall survival, overall response rate and complete
response rate (with or without complete blood count recovery).
About the VIALE-A Study
VIALE-A [NCT02993523] is a Phase III, randomized, double-blind,
placebo-controlled multicenter study evaluating the efficacy and
safety of Venclexta® (venetoclax) plus azacitidine, a
hypomethylating agent, compared to placebo with azacitidine, in 431
people with previously untreated acute myeloid leukemia who are
ineligible for intensive chemotherapy. Two-thirds of patients
(n=286) received 400 mg Venclexta daily, in combination with
azacitidine, and the remaining patients (n=145) received placebo
tablets in combination with azacitidine. Patients enrolled in the
study had a range of mutational subtypes, including IDH1/2 and
FLT3. VIALE-A met its primary and key secondary endpoints.
About Venclexta
Venclexta is a first-in-class targeted medicine designed to
selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein.
In some blood cancers and other tumors, BCL-2 builds up and
prevents cancer cells from dying or self-destructing, a process
called apoptosis. Venclexta blocks the BCL-2 protein and works to
restore the process of apoptosis.
Venclexta is being developed by AbbVie and Genentech, a member
of the Roche Group. It is jointly commercialized by the companies
in the United States and commercialized by AbbVie outside of the
United States. Together, the companies are committed to research
with Venclexta, which is currently being studied in clinical trials
across several types of blood cancers.
In the United States, Venclexta has been granted five
Breakthrough Therapy Designations by the U.S. Food and Drug
Administration (FDA): one for previously untreated CLL, two for
relapsed or refractory CLL and two for previously untreated acute
myeloid leukemia.
Venclexta Indications
Venclexta is a prescription medicine used:
- to treat adults with chronic lymphocytic leukemia (CLL) or
small lymphocytic lymphoma (SLL).
- in combination with azacitidine, or decitabine, or low-dose
cytarabine to treat adults with newly-diagnosed acute myeloid
leukemia (AML) who:
- are 75 years of age or older, or
- have other medical conditions that prevent the use of standard
chemotherapy.
It is not known if Venclexta is safe and effective in
children.
Important Safety Information
What is the most important information patients should know
about Venclexta?
Venclexta can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast
breakdown of cancer cells. TLS can cause kidney failure, the need
for dialysis treatment, and may lead to death. The patient’s doctor
will do tests to check their risk of getting TLS before they start
taking Venclexta. The patient will receive other medicines before
starting and during treatment with Venclexta to help reduce the
risk of TLS. The patient may also need to receive intravenous (IV)
fluids into their vein.
The patient’s doctor will do blood tests to check for TLS when
the patient first starts treatment and during treatment with
Venclexta. It is important for patients to keep appointments for
blood tests. Patients should tell their doctor right away if they
have any symptoms of TLS during treatment with Venclexta, including
fever, chills, nausea, vomiting, confusion, shortness of breath,
seizures, irregular heartbeat, dark or cloudy urine, unusual
tiredness, or muscle or joint pain.
Patients should drink plenty of water during treatment with
Venclexta to help reduce the risk of getting TLS.
Patients should drink 6 to 8 glasses (about 56 ounces total) of
water each day, starting 2 days before the first dose on the day of
the first dose of Venclexta, and each time a dose is increased.
The patient’s doctor may delay, decrease the dose, or stop
treatment with Venclexta if the patient has side effects. When
restarting Venclexta after stopping for 1 week or longer, the
patient’s doctor may again check for the risk of TLS and change the
patient’s dose.
What patients should not take Venclexta?
Certain medicines must not be taken when the patient first
starts taking Venclexta and while the dose is being slowly
increased because of the risk of increased TLS.
- Patients should tell their doctor about all the medicines
they take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements. Venclexta and other
medicines may affect each other causing serious side effects.
- Patients must not start new medicines during treatment with
Venclexta without first talking with their doctor.
Before taking Venclexta, patients must tell their doctor
about all of their medical conditions, including if they:
- Have kidney or liver problems.
- Have problems with body salts or electrolytes, such as
potassium, phosphorus, or calcium.
- Have a history of high uric acid levels in the blood or
gout.
- Are scheduled to receive a vaccine. Patients should not receive
a “live vaccine” before, during, or after treatment with Venclexta,
until the patient’s doctor tells them it is okay. If the patient is
not sure about the type of immunization or vaccine, the patient
should ask their doctor. These vaccines may not be safe or may not
work as well during treatment with Venclexta.
- Are pregnant or plan to become pregnant. Venclexta may harm an
unborn baby. If the patient is able to become pregnant, the
patient’s doctor should do a pregnancy test before the patient
starts treatment with Venclexta, and the patient should use
effective birth control during treatment and for at least 30 days
after the last dose of Venclexta. If the patient becomes pregnant
or thinks they are pregnant, the patient should tell their doctor
right away.
- Are breastfeeding or plan to breastfeed. It is not known if
Venclexta passes into the patient’s breast milk. Patients are
instructed to not breastfeed during treatment with Venclexta and
for 1 week after the last dose.
What to avoid while taking Venclexta:
Patients should not drink grapefruit juice or eat grapefruit,
Seville oranges (often used in marmalades), or starfruit while they
are taking Venclexta. These products may increase the amount of
Venclexta in the patient’s blood.
What are the possible side effects of Venclexta?
Venclexta can cause serious side effects, including:
- Low white blood cell counts (neutropenia). Low white
blood cell counts are common with Venclexta, but can also be
severe. The patient’s doctor will do blood tests to check their
blood counts during treatment with Venclexta and may pause
dosing.
- Infections. Death and serious infections such as
pneumonia and blood infection (sepsis) have happened during
treatment with Venclexta. The patient’s doctor will closely monitor
and treat the patient right away if they have a fever or any signs
of infection during treatment with Venclexta.
Patients should tell their doctor right away if they have a
fever or any signs of an infection during treatment with
Venclexta.
The most common side effects of Venclexta when used in
combination with obinutuzumab or rituximab or alone in people with
CLL or SLL include low white blood cell count; low platelet
count; low red blood cell count; diarrhea; nausea; upper
respiratory tract infection; cough; muscle and joint pain;
tiredness; and swelling of arms, legs, hands, and feet.
The most common side effects of Venclexta in combination with
azacitidine or decitabine or low-dose cytarabine in people with AML
include nausea; diarrhea; low platelet count; constipation; low
white blood cell count; fever with low white blood cell count;
tiredness; vomiting; swelling of arms, legs, hands, or feet; fever;
infection in lungs; shortness of breath; bleeding; low red blood
cell count; rash; stomach (abdominal) pain; infection in your
blood; muscle and joint pain; dizziness; cough; sore throat; and
low blood pressure.
Venclexta may cause fertility problems in males. This may affect
the ability to father a child. Patients should talk to their doctor
if they have concerns about fertility.
These are not all the possible side effects of Venclexta.
Patients should call their doctor for medical advice about side
effects.
Report side effects to the FDA at 1-800-FDA-1088 or
http://www.fda.gov/medwatch. Report side effects to Genentech at
1-888-835-2555.
Please see the Venclexta full Prescribing Information,
including the Medication Guide, for additional Important Safety
Information.
About Genentech in Hematology
For more than 20 years, Genentech has been developing medicines
with the goal to redefine treatment in hematology. Today, we’re
investing more than ever in our effort to bring innovative
treatment options to people with diseases of the blood. For more
information visit http://www.gene.com/hematology.
About Genentech
Founded more than 40 years ago, Genentech is a leading
biotechnology company that discovers, develops, manufactures and
commercializes medicines to treat patients with serious and
life-threatening medical conditions. The company, a member of the
Roche Group, has headquarters in South San Francisco, California.
For additional information about the company, please visit
http://www.gene.com.
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