Phase 3 Trial of NINLARO (ixazomib) as Maintenance Therapy Met Primary Endpoint Demonstrating Statistically Significant Improvement in Progression-Free Survival in Patients with Multiple Myeloma Post-Transplant

Takeda Pharmaceutical Company Limited (TSE:
4502) today announced that the randomized, Phase 3 TOURMALINE-MM3
study met its primary endpoint, demonstrating single-agent oral NINLARO®
(ixazomib) as a maintenance therapy resulted in a statistically
significant improvement in progression-free survival (PFS) versus
placebo. The trial evaluated the effect of NINLARO as a maintenance
therapy in adult patients diagnosed with multiple myeloma who responded
to high-dose therapy (HDT) and autologous stem cell transplant (ASCT).
Takeda plans to submit data from the trial to regulatory agencies around
the world. NINLARO is currently not approved as a maintenance therapy
for multiple myeloma following ASCT.

“Within the maintenance setting, it is critical that we find agents that
are efficacious, tolerable and convenient,” said Jesús Gomez Navarro,
M.D., Vice President, Head of Oncology Clinical Research and
Development, Takeda. “The results of the TOURMALINE-MM3 trial represent
an important step toward the goal of expanding the use of NINLARO as a
maintenance therapy. This is the first and only Phase 3
placebo-controlled study evaluating a proteasome inhibitor in this
setting and we look forward to discussions with Health Authorities
around the world.”

There were no new safety signals found in TOURMALINE-MM3. The safety
profile of NINLARO in the maintenance setting is consistent with
previously reported results of single-agent NINLARO use.

Full data results will be submitted for presentation at the 60th
American Society of Hematology Annual Meeting in December.

About the TOURMALINE-MM3 Trial

TOURMALINE-MM3 is a randomized, placebo-controlled, double-blind Phase 3
study of 656 patients, designed to determine the effect of NINLARO®
(ixazomib) maintenance therapy on progression-free survival (PFS),
compared to placebo, in participants with multiple myeloma who have had
a response (complete response [CR], very good partial response [VGPR],
or partial response [PR]) to induction therapy followed by high-dose
therapy (HDT) and autologous stem cell transplant (ASCT). The primary
endpoint is progression-free survival (PFS). A key secondary endpoint
includes overall survival (OS). For additional information: https://www.clinicaltrials.gov/ct2/show/NCT02181413.

About NINLARO® (ixazomib) capsules

NINLARO® (ixazomib) is an oral proteasome inhibitor which is
also being studied across the continuum of multiple myeloma treatment
settings as well as systemic light-chain (AL) amyloidosis. It was the
first oral proteasome inhibitor to enter Phase 3 clinical trials and to
receive approval. NINLARO was approved by the U.S. Food and Drug
Administration (FDA) in November 2015 following a priority review and by
the European Commission in November 2016. In the U.S. and Europe,
NINLARO is indicated in combination with lenalidomide and dexamethasone
for the treatment of patients with multiple myeloma who have received at
least one prior therapy. NINLARO has received marketing authorization by
regulatory authorities in more than 55 countries.

Ixazomib was granted orphan drug designation in multiple myeloma in both
the U.S. and Europe in 2011 and for AL amyloidosis in both the U.S. and
Europe in 2012. Ixazomib received Breakthrough Therapy status by the
U.S. FDA for relapsed or refractory systemic light-chain (AL)
amyloidosis, a related ultra orphan disease, in 2014. The Japanese
Ministry of Health, Labour and Welfare granted Orphan Drug designation
to ixazomib in 2016.

The comprehensive ixazomib clinical development program, TOURMALINE,
includes a total of six ongoing pivotal trials – five, which together
are investigating every major multiple myeloma patient population, and
one in light-chain amyloidosis:

For more information about actively enrolling Phase 3 studies please
visit: https://www.tourmalinetrials.com/

In addition to the TOURMALINE program, ixazomib is being evaluated in
multiple therapeutic combinations for various patient populations in
investigator initiated studies globally.

NINLARO® (ixazomib) capsules: Global
Important Safety Information

SPECIAL WARNINGS AND PRECAUTIONSThrombocytopenia has
been reported with NINLARO (28% vs. 14% in the NINLARO and placebo
regimens, respectively) with platelet nadirs typically occurring between
Days 14-21 of each 28-day cycle and recovery to baseline by the start of
the next cycle. It did not result in an increase in hemorrhagic events
or platelet transfusions. Monitor platelet counts at least monthly
during treatment with NINLARO and consider more frequent monitoring
during the first three cycles. Manage with dose modifications and
platelet transfusions as per standard medical guidelines.

Gastrointestinal toxicities have been reported in the NINLARO and
placebo regimens respectively, such as diarrhea (42% vs. 36%),
constipation (34% vs. 25%), nausea (26% vs. 21%), and vomiting (22% vs.
11%), occasionally requiring use of antiemetic and anti-diarrheal
medications, and supportive care.

Peripheral neuropathy was reported with NINLARO (28% vs. 21% in
the NINLARO and placebo regimens, respectively). The most commonly
reported reaction was peripheral sensory neuropathy (19% and 14% in the
NINLARO and placebo regimens, respectively). Peripheral motor neuropathy
was not commonly reported in either regimen (< 1%). Monitor patients for
symptoms of peripheral neuropathy and adjust dosing as needed.

Peripheral edema was reported with NINLARO (25% vs. 18% in the
NINLARO and placebo regimens, respectively). Evaluate patients for
underlying causes and provide supportive care, as necessary. Adjust the
dose of dexamethasone per its prescribing information or the dose of
NINLARO for severe symptoms.

Cutaneous reactions occurred in 19% of patients in the NINLARO
regimen compared to 11% of patients in the placebo regimen. The most
common type of rash reported in both regimens was maculo-papular and
macular rash. Manage rash with supportive care, dose modification or
discontinuation.

Hepatotoxicity, drug-induced liver injury, hepatocellular injury,
hepatic steatosis, and hepatitis cholestatic have been uncommonly
reported with NINLARO. Monitor hepatic enzymes regularly and adjust dose
for Grade 3 or 4 symptoms.

Pregnancy- NINLARO can cause fetal harm. Advise male and females
patients of reproductive potential to use contraceptive measures during
treatment and for an additional 90 days after the final dose of NINLARO.
Women of childbearing potential should avoid becoming pregnant while
taking NINLARO due to potential hazard to the fetus. Women using
hormonal contraceptives should use an additional barrier method of
contraception.

Lactation- It is not known whether NINLARO or its metabolites are
excreted in human milk. There could be potential adverse events in
nursing infants and therefore breastfeeding should be discontinued.

SPECIAL PATIENT POPULATIONSHepatic Impairment:
Reduce the NINLARO starting dose to 3 mg in patients with
moderate or severe hepatic impairment.

Renal Impairment: Reduce the NINLARO starting dose to 3 mg
in patients with severe renal impairment or end-stage renal disease
(ESRD) requiring dialysis. NINLARO is not dialyzable and, therefore, can
be administered without regard to the timing of dialysis.

DRUG INTERACTIONSCo-administration of strong CYP3A inducers
with NINLARO is not recommended.

ADVERSE REACTIONSThe most frequently reported adverse
reactions (? 20%) in the NINLARO regimen, and greater than in the
placebo regimen, were diarrhea (42% vs. 36%), constipation (34% vs.
25%), thrombocytopenia (28% vs. 14%), peripheral neuropathy (28% vs.
21%), nausea (26% vs. 21%), peripheral edema (25% vs. 18%), vomiting
(22% vs. 11%), and back pain (21% vs. 16%). Serious adverse reactions
reported in ? 2% of patients included thrombocytopenia (2%) and diarrhea
(2%). For each adverse reaction, one or more of the three drugs was
discontinued in ? 1% of patients in the NINLARO regimen.

For European Union Summary of Product Characteristics: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdfFor
US Prescribing Information: https://www.ninlarohcp.com/pdf/prescribing-information.pdfFor
Canada Product Monograph: http://www.takedacanada.com/ninlaropm

About Takeda Pharmaceutical CompanyTakeda Pharmaceutical
Company Limited (TSE: 4502) is a global, research and development-driven
pharmaceutical company committed to bringing better health and a
brighter future to patients by translating science into life-changing
medicines. Takeda focuses its R&D efforts on oncology, gastroenterology
and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D
both internally and with partners to stay at the leading edge of
innovation. Innovative products, especially in oncology and
gastroenterology, as well as Takeda’s presence in emerging markets, are
currently fueling the growth of Takeda. Approximately 30,000 Takeda
employees are committed to improving quality of life for patients,
working with Takeda’s partners in health care in more than 70 countries.

For more information, visit https://www.takeda.com/newsroom/.

Additional information about Takeda is available through its corporate
website, www.takeda.com,
and additional information about Takeda Oncology, the brand for the
global oncology business unit of Takeda Pharmaceutical Company Limited,
is available through its website, www.takedaoncology.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20180711005052/en/

Leave a Comment