-$20 Million Milestone Payment Triggered by Annual ADCETRIS Net Sales
Exceeding $200 Million in Takeda’s Territory During 2015-
-European Commission Recently Approved a Type II Label Variation that
Includes Data on the Retreatment of Relapsed or Refractory (R/R) Hodgkin
lymphoma or R/R Systemic ALCL-
BOTHELL, Wash.–(BUSINESS WIRE)–Seattle Genetics, Inc., (Nasdaq: SGEN) today announced that it will
receive a one-time $20 million milestone payment under its ADCETRIS
(brentuximab vedotin) collaboration with Takeda Pharmaceutical Company
Limited (Takeda). The milestone was triggered by Takeda surpassing
annual ADCETRIS net sales of $200 million in its territory during 2015.
The milestone will be recognized as royalty revenue in the first quarter
of 2016. In addition, the company announced that the European Commission
recently approved a Type II variation that includes data on the
retreatment of adult patients with relapsed or refractory (R/R) Hodgkin
lymphoma or R/R systemic anaplastic large cell lymphoma (sALCL) who
previously responded to ADCETRIS and who later relapse. The label update
follows a positive opinion from the Committee for Medicinal Products for
Human Use (CHMP) in October 2015.
“This sales milestone and recent label update in Europe to include data
on retreatment underscore the strong commercial and regulatory progress
that Takeda has made in its territory,” said Clay B. Siegall, Ph.D.,
President and Chief Executive Officer at Seattle Genetics. “We and
Takeda are focused on the goal of establishing ADCETRIS as the
foundation of care for CD30-expressing lymphomas through global
commercialization activities and a broad clinical development program
that includes three phase 3 trials.”
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the
terms of the collaboration agreement, Seattle Genetics has U.S. and
Canadian commercialization rights and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Seattle Genetics is entitled to
royalties based on a percentage of Takeda’s net sales in its territory
at rates that range from the mid-teens to the mid-twenties based on
sales volume subject to offsets for royalties paid by Takeda to third
parties. In addition, Seattle Genetics is entitled to receive progress-
and sales-dependent milestone payments based on net sales of ADCETRIS
within Takeda’s licensed territory. Seattle Genetics and Takeda are
funding joint development costs for ADCETRIS on a 50:50 basis, except in
Japan where Takeda is solely responsible for development costs.
About ADCETRIS® (Brentuximab Vedotin)
is an ADC comprising an anti-CD30 monoclonal antibody attached by a
protease-cleavable linker to a microtubule disrupting agent, monomethyl
auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology.
The ADC employs a linker system that is designed to be stable in the
bloodstream but to release MMAE upon internalization into
CD30-expressing tumor cells. CD30 is a member of the tumor necrosis
factor receptor (TNFR) superfamily. In HL, CD30 may be involved in tumor
cell proliferation by interacting with immune cells in the tumor
ADCETRIS for intravenous injection has received approval from the FDA
for three indications: (1) regular approval for the treatment of
patients with classical HL after failure of autologous hematopoietic
stem cell transplantation (auto-HSCT) or after failure of at least two
prior multi-agent chemotherapy regimens in patients who are not
auto-HSCT candidates, (2) regular approval for the treatment of
classical HL patients at high risk of relapse or progression as
post-auto-HSCT consolidation, and (3) accelerated approval for the
treatment of patients with systemic anaplastic large cell lymphoma
(sALCL) after failure of at least one prior multi-agent chemotherapy
regimen. The sALCL indication is approved under accelerated approval
based on overall response rate. Continued approval for the sALCL
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. Health Canada granted ADCETRIS
approval with conditions for relapsed or refractory HL and sALCL.
ADCETRIS was granted conditional marketing authorization by the European
Commission in October 2012 for two indications: (1) for the treatment of
adult patients with relapsed or refractory CD30-positive HL following
autologous stem cell transplant (ASCT), or following at least two prior
therapies when ASCT or multi-agent chemotherapy is not a treatment
option, and (2) the treatment of adult patients with relapsed or
refractory sALCL. In January 2016, the European Commission approved a
Type II variation to include data on the retreatment of adult patients
with Hodgkin lymphoma or sALCL who previously responded to ADCETRIS and
who later relapse. ADCETRIS has received marketing authorization by
regulatory authorities in 60 countries. See important safety information
About Seattle Genetics
Seattle Genetics is a biotechnology
company focused on the development and commercialization of innovative
antibody-based therapies for the treatment of cancer. Seattle Genetics
is leading the field in developing antibody-drug conjugates (ADCs), a
technology designed to harness the targeting ability of antibodies to
deliver cell-killing agents directly to cancer cells. The company’s lead
product, ADCETRIS® (brentuximab vedotin), is a CD30-targeted
ADC that, in collaboration with Takeda Pharmaceutical Company Limited,
is commercially available in 60 countries, including the U.S., Canada,
Japan and members of the European Union. Additionally, ADCETRIS is being
evaluated broadly in more than 70 ongoing clinical trials in
CD30-expressing malignancies. Seattle Genetics is also advancing
vadastuximab talirine (SGN-CD33A; 33A), an ADC that is expected to
advance into a phase 3 trial for acute myeloid leukemia in 2016. Beyond
ADCETRIS and 33A, the company is developing a robust pipeline of
clinical-stage programs, including denintuzumab mafodotin (SGN-CD19A;
19A), SGN-LIV1A, ASG-15ME, ASG-22ME (enfortumab vedotin), SGN-CD70A and
SEA-CD40. Seattle Genetics has collaborations for its ADC technology
with a number of leading biotechnology and pharmaceutical companies,
including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech,
GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
ADCETRIS (brentuximab vedotin) U.S. Important Safety Information
Progressive multifocal leukoencephalopathy
(PML): JC virus infection resulting in PML and death can occur in
patients receiving ADCETRIS® (brentuximab
ADCETRIS is contraindicated with
concomitant bleomycin due to pulmonary toxicity (e.g., interstitial
infiltration and/or inflammation).
Warnings and Precautions
Peripheral neuropathy: ADCETRIS treatment causes a peripheral
neuropathy that is predominantly sensory. Cases of peripheral motor
neuropathy have also been reported. ADCETRIS-induced peripheral
neuropathy is cumulative. Monitor patients for symptoms of neuropathy,
such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a
burning sensation, neuropathic pain or weakness and institute dose
Anaphylaxis and infusion reactions: Infusion-related reactions,
including anaphylaxis, have occurred with ADCETRIS. Monitor patients
during infusion. If an infusion-related reaction occurs, interrupt the
infusion and institute appropriate medical management. If anaphylaxis
occurs, immediately and permanently discontinue the infusion and
administer appropriate medical therapy.
Hematologic toxicities: Prolonged (≥1 week) severe neutropenia
and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.
Febrile neutropenia has been reported with ADCETRIS. Monitor complete
blood counts prior to each dose of ADCETRIS and consider more frequent
monitoring for patients with Grade 3 or 4 neutropenia. Monitor
patients for fever. If Grade 3 or 4 neutropenia develops, consider
dose delays, reductions, discontinuation, or G-CSF prophylaxis with
Serious infections and opportunistic infections: Infections
such as pneumonia, bacteremia, and sepsis or septic shock (including
fatal outcomes) have been reported in patients treated with ADCETRIS.
Closely monitor patients during treatment for the emergence of
possible bacterial, fungal or viral infections.
Tumor lysis syndrome: Closely monitor patients with rapidly
proliferating tumor and high tumor burden.
Increased toxicity in the presence of severe renal impairment: The
frequency of ≥Grade 3 adverse reactions and deaths was greater in
patients with severe renal impairment compared to patients with normal
renal function. Avoid the use of ADCETRIS in patients with severe
Increased toxicity in the presence of moderate or severe hepatic
impairment: The frequency of ≥Grade 3 adverse reactions and deaths
was greater in patients with moderate or severe hepatic impairment
compared to patients with normal hepatic function. Avoid the use of
ADCETRIS in patients with moderate or severe hepatic impairment.
Hepatotoxicity: Serious cases of hepatotoxicity, including
fatal outcomes, have occurred with ADCETRIS. Cases were consistent
with hepatocellular injury, including elevations of transaminases
and/or bilirubin, and occurred after the first dose of ADCETRIS or
rechallenge. Preexisting liver disease, elevated baseline liver
enzymes, and concomitant medications may also increase the risk.
Monitor liver enzymes and bilirubin. Patients experiencing new,
worsening, or recurrent hepatotoxicity may require a delay, change in
dose, or discontinuation of ADCETRIS.
Progressive multifocal leukoencephalopathy (PML): JC virus
infection resulting in PML and death has been reported in
ADCETRIS-treated patients. First onset of symptoms occurred at various
times from initiation of ADCETRIS therapy, with some cases occurring
within 3 months of initial exposure. In addition to ADCETRIS therapy,
other possible contributory factors include prior therapies and
underlying disease that may cause immunosuppression. Consider the
diagnosis of PML in any patient presenting with new-onset signs and
symptoms of central nervous system abnormalities. Hold ADCETRIS if PML
is suspected and discontinue ADCETRIS if PML is confirmed.
Pulmonary Toxicity: Events of noninfectious pulmonary toxicity
including pneumonitis, interstitial lung disease, and acute
respiratory distress syndrome, some with fatal outcomes, have been
reported. Monitor patients for signs and symptoms of pulmonary
toxicity, including cough and dyspnea. In the event of new or
worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation
and until symptomatic improvement.
Serious dermatologic reactions: Stevens-Johnson syndrome (SJS)
and toxic epidermal necrolysis (TEN), including fatal outcomes, have
been reported with ADCETRIS. If SJS or TEN occurs, discontinue
ADCETRIS and administer appropriate medical therapy.
Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant
women of the potential hazard to the fetus.
Most Common Adverse Reactions:
ADCETRIS was studied as
monotherapy in 160 patients with relapsed classical HL and sALCL in two
uncontrolled single-arm trials. Across both trials, the most common
adverse reactions (≥20%), regardless of causality, were neutropenia,
peripheral sensory neuropathy, fatigue, nausea, anemia, upper
respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia,
cough and vomiting.
ADCETRIS was studied in 329 patients with classical HL at high risk of
relapse or progression post-auto-HSCT in a placebo-controlled randomized
trial. The most common adverse reactions (≥20%) in the
ADCETRIS-treatment arm (167 patients), regardless of causality, were
neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia,
upper respiratory tract infection, fatigue, peripheral motor neuropathy,
nausea, cough, and diarrhea.
Concomitant use of strong CYP3A4
inhibitors or inducers, or P-gp inhibitors, has the potential to affect
the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse
reactions are increased in patients with moderate or severe hepatic
impairment or severe renal impairment. Avoid use.
For additional Important Safety Information, including Boxed WARNING,
please see the full Prescribing Information for ADCETRIS at https://laprensafl.files.wordpress.com/2015/10/adcetris_uspi.pdf.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the potential
commercial opportunity for ADCETRIS and the potential for approval of
ADCETRIS in other countries and for other disease settings. Actual
results or developments may differ materially from those projected or
implied in these forward-looking statements. Factors that may cause such
a difference include risks that ADCETRIS may not receive the regulatory
approvals expected or even if regulatory approvals are obtained, payment
and reimbursement for the use of ADCETRIS may be less than projected.
More information about the risks and uncertainties faced by Seattle
Genetics is contained in the company’s 10-Q for the quarter ended
September 30, 2015 filed with the Securities and Exchange Commission.
Seattle Genetics disclaims any intention or obligation to update or
revise any forward-looking statements, whether as a result of new
information, future events or otherwise.