Seattle Genetics expands Adcetris indications in Canada

May 3, 2019 Off By BusinessWire

-Health Canada Approves ADCETRIS in Combination with AVD Chemotherapy
for the Treatment of Previously Untreated Hodgkin Lymphoma Based on
Positive Phase 3 ECHELON-1 Clinical Trial Results-

-Supplemental New Drug Submission Completed for ADCETRIS in
Combination with CHP Chemotherapy in Frontline Peripheral T-Cell
Lymphoma based on Positive Phase 3 ECHELON-2 Clinical Trial Results and
Granted Priority Review Designation by Health Canada-

BOTHELL, Wash.–(BUSINESS WIRE)–Seattle
Genetics, Inc. (Nasdaq:SGEN) today announced that Health Canada has
approved the supplemental New Drug Submission that expands the use of
ADCETRIS (brentuximab vedotin) in combination with AVD (Adriamycin,
vinblastine and dacarbazine) chemotherapy in patients with previously
untreated Stage IV Hodgkin lymphoma (HL). The approval is based on
positive results of the phase 3 ECHELON-1 clinical trial that compared
ADCETRIS plus AVD to ABVD (Adriamycin, bleomycin, vinblastine and
dacarbazine). In addition, a supplemental New Drug Submission was
recently submitted to Health Canada for ADCETRIS in combination with CHP
(cyclophosphamide, doxorubicin, prednisone) in patients with previously
untreated CD30-expressing peripheral T-cell lymphoma (PTCL) based on the
positive phase 3 ECHELON-2 clinical trial results. Health Canada granted
a Priority Review Designation for this submission. ADCETRIS is an
antibody-drug conjugate (ADC) directed to CD30, a defining marker of
classical HL and expressed on the surface of several types of PTCL.

“The Health Canada approval of ADCETRIS in combination with AVD
chemotherapy in advanced-stage (Stage IV) Hodgkin lymphoma represents
the first major advance for patients in decades,” said Kerry Savage,
M.D., Medical Oncologist at the BC Cancer Agency, Professor of Medicine
at the University of British Columbia and investigator on both the phase
3 ECHELON-1 and ECHELON-2 clinical trials. “Advanced-stage Hodgkin
lymphoma tends to be more aggressive and difficult to treat. This new
ADCETRIS-containing regimen demonstrated superior efficacy when compared
to the standard of care ABVD chemotherapy in the phase 3 ECHELON-1
clinical trial supporting the Health Canada approval and represents a
meaningful advance for this Hodgkin lymphoma patient population.”

“Currently, up to 30 percent of newly diagnosed patients with
advanced-stage Hodgkin lymphoma will experience disease progression
after treatment with the current standard of care, representing a
significant need for improved treatment options,” said Clay Siegall,
Ph.D., President and Chief Executive Officer of Seattle Genetics. “With
this new indication for ADCETRIS, physicians and eligible patients in
Canada have access to this important new regimen for treating Stage IV
Hodgkin lymphoma. We also recently submitted a supplemental New Drug
Submission application to Health Canada, which was granted Priority
Review Designation, for ADCETRIS in combination with chemotherapy in
frontline PTCL, a milestone supporting our plans to expand ADCETRIS
globally to patients in need.”

In March
2018, the U.S. Food and Drug Administration (FDA) approved ADCETRIS
in combination with AVD for the treatment of adult patients with
previously untreated stage III or IV classical HL based on the results
of the phase 3 ECHELON-1 clinical trial. In November
2018, the FDA approved ADCETRIS in combination with CHP for the
treatment of adult patients with previously untreated systemic
anaplastic large cell lymphoma (sALCL) or other CD30-expressing PTCL,
including angioimmunoblastic T-cell lymphoma and PTCL not otherwise
specified.

About Classical Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the
lymphatic system. There are two major categories of lymphoma: Hodgkin
lymphoma and non-Hodgkin lymphoma. Classical Hodgkin lymphoma is
distinguished from other types of lymphoma by the presence of one
characteristic type of cell, known as the Reed-Sternberg cell. The
Reed-Sternberg cell expresses CD30.

About T-Cell Lymphomas

There are more than 60 subtypes of non-Hodgkin lymphomas which are
broadly divided into two major groups: B-cell lymphomas, which develop
from abnormal B-lymphocytes, and T-cell lymphomas, which develop from
abnormal T-lymphocytes. There are many different forms of T-cell
lymphomas, some of which are extremely rare. T-cell lymphomas can be
aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for
approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and
Europe and may be as high as 24 percent in parts of Asia.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 clinical trials in
CD30-expressing lymphomas. These include three completed phase 3 trials:
ECHELON-2 trial in frontline peripheral T-cell lymphomas, ECHELON-1 in
previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell
lymphoma. The ongoing CHECKMATE 812 trial of ADCETRIS in combination
with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma
is ongoing.

ADCETRIS 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.

ADCETRIS injection for intravenous infusion has received FDA approval
for six indications in adult patients with: (1) previously untreated
systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing
peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell
lymphoma and PTCL not otherwise specified, in combination with
cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated
Stage III or IV classical Hodgkin lymphoma (cHL), in combination with
doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of
relapse or progression as post-autologous hematopoietic stem cell
transplantation (auto-HSCT) consolidation, (4) cHL after failure of
auto-HSCT or failure of at least two prior multi-agent chemotherapy
regimens in patients who are not auto-HSCT candidates, (5) sALCL after
failure of at least one prior multi-agent chemotherapy regimen, and (6)
primary cutaneous anaplastic large cell lymphoma (pcALCL) or
CD30-expressing mycosis fungoides (MF) who have received prior systemic
therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or
refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional
approval for post-autologous stem cell transplantation (ASCT)
consolidation treatment of Hodgkin lymphoma patients at increased risk
of relapse or progression in 2017, adults with pcALCL or CD30-expressing
MF who have had prior systemic therapy in 2018, and for previously
untreated Stage IV Hodgkin lymphoma in combination with doxorubicin,
vinblastine, and dacarbazine in 2019.

ADCETRIS received conditional marketing authorization from the European
Commission in October 2012. The approved indications in Europe are: (1)
for the treatment of adult patients with relapsed or refractory
CD30-positive Hodgkin lymphoma following ASCT, or following at least two
prior therapies when ASCT or multi-agent chemotherapy is not a treatment
option, (2) for the treatment of adult patients with relapsed or
refractory sALCL, (3) for the treatment of adult patients with
CD30-positive Hodgkin lymphoma at increased risk of relapse or
progression following ASCT, (4) for the treatment of adult patients with
CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior
systemic therapy and (5) for the treatment of adult patients with
previously untreated CD30-positive Stage IV Hodgkin lymphoma in
combination with AVD (Adriamycin^®, vinblastine and
dacarbazine).

ADCETRIS has received marketing authorization by regulatory authorities
in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL.
See select important safety information, including Boxed Warning, below.

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 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 Seattle Genetics

Seattle Genetics, Inc. is an emerging multi-product, global
biotechnology company that develops and commercializes transformative
therapies targeting cancer to make a meaningful difference in people’s
lives. ADCETRIS^® (brentuximab vedotin) utilizes the company’s
industry-leading antibody-drug conjugate (ADC) technology and is
currently approved for the treatment of multiple CD30-expressing
lymphomas. Beyond ADCETRIS, the company has established a pipeline of
novel targeted therapies at various stages of clinical testing,
including three in ongoing pivotal trials for solid tumors. Enfortumab
vedotin for metastatic urothelial cancer and tisotumab vedotin for
metastatic cervical cancer utilize our proprietary ADC technology.
Tucatinib, a small molecule tyrosine kinase inhibitor, is in a pivotal
trial for HER2-positive metastatic breast cancer. In addition, we are
leveraging our expertise in empowered antibodies to build a portfolio of
proprietary immuno-oncology agents in clinical trials targeting
hematologic malignancies and solid tumors. The company is headquartered
in Bothell, Washington, and has a European office in Switzerland. For
more information on our robust pipeline, visit www.seattlegenetics.com
and follow @SeattleGenetics on Twitter.

ADCETRIS (brentuximab vedotin) U.S. Important Safety Information

BOXED WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML):
JC
virus infection resulting in PML and death can occur in ADCETRIS-treated
patients.

Contraindication

ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g.,
interstitial infiltration and/or inflammation).

Warnings and Precautions

- Peripheral neuropathy (PN): ADCETRIS causes PN that is
  predominantly sensory. Cases of motor PN have also been reported.
  ADCETRIS-induced PN is cumulative. Monitor for symptoms such as
  hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning
  sensation, neuropathic pain, or weakness. Institute dose modifications
  accordingly.

- Anaphylaxis and infusion reactions: Infusion-related reactions
  (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor
  patients during infusion. If an IRR occurs, interrupt the infusion and
  institute appropriate medical management. If anaphylaxis occurs,
  immediately and permanently discontinue the infusion and administer
  appropriate medical therapy. Premedicate patients with a prior IRR
  before subsequent infusions. Premedication may include acetaminophen,
  an antihistamine, and a corticosteroid.

- Hematologic toxicities: Fatal and serious cases of febrile
  neutropenia have been reported with ADCETRIS. Prolonged (≥1 week)
  severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can
  occur with ADCETRIS. Start primary prophylaxis with G-CSF beginning
  with Cycle 1 for patients who receive ADCETRIS in combination with
  chemotherapy for previously untreated Stage III or IV classical HL or
  previously untreated PTCL. Monitor complete blood counts prior to each
  ADCETRIS dose. Monitor more frequently 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 subsequent ADCETRIS doses.

- Serious infections and opportunistic infections: Infections
  such as pneumonia, bacteremia, and sepsis or septic shock (including
  fatal outcomes) have been reported in ADCETRIS-treated patients.
  Closely monitor patients during treatment for 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 use in patients with severe renal impairment.

- 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 use in
  patients with moderate or severe hepatic impairment.

- Hepatotoxicity: Fatal and serious cases have occurred in
  ADCETRIS-treated patients. Cases were consistent with hepatocellular
  injury, including elevations of transaminases and/or bilirubin, and
  occurred after the first ADCETRIS dose or rechallenge. Preexisting
  liver disease, elevated baseline liver enzymes, and concomitant
  medications may increase the risk. Monitor liver enzymes and
  bilirubin. Patients with new, worsening, or recurrent hepatotoxicity
  may require a delay, change in dose, or discontinuation of ADCETRIS.

- PML: Fatal cases of JC virus infection resulting in PML and
  death have 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. Other possible contributory factors other than ADCETRIS
  include prior therapies and underlying disease that may cause
  immunosuppression. Consider PML diagnosis in patients 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: Fatal and serious events of noninfectious
  pulmonary toxicity including pneumonitis, interstitial lung disease,
  and acute respiratory distress syndrome have been reported. Monitor
  patients for signs and symptoms, 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: Fatal and serious cases of
  Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
  have been reported with ADCETRIS. If SJS or TEN occurs, discontinue
  ADCETRIS and administer appropriate medical therapy.

- Gastrointestinal (GI) complications: Fatal and serious cases of
  acute pancreatitis have been reported. Other fatal and serious GI
  complications include perforation, hemorrhage, erosion, ulcer,
  intestinal obstruction, enterocolitis, neutropenic colitis, and ileus.
  Lymphoma with preexisting GI involvement may increase the risk of
  perforation. In the event of new or worsening GI symptoms, perform a
  prompt diagnostic evaluation and treat appropriately.

- Embryo-fetal toxicity: Based on the mechanism of action and
  animal studies, ADCETRIS can cause fetal harm. Advise females of
  reproductive potential of the potential risk to the fetus, and to
  avoid pregnancy during ADCETRIS treatment and for at least 6 months
  after the final dose of ADCETRIS.

Most Common (≥20% in any study) Adverse Reactions: Peripheral
neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory
tract infection, pyrexia, constipation, vomiting, alopecia, decreased
weight, abdominal pain, anemia, stomatitis, lymphopenia and mucositis

Drug Interactions

Concomitant use of strong CYP3A4 inhibitors or inducers has the
potential to affect the exposure to monomethyl auristatin E (MMAE).

Use in Specific Populations

Moderate or severe hepatic impairment or severe renal impairment: MMAE
exposure and adverse reactions are increased. Avoid use.

Advise males with female sexual partners of reproductive potential to
use effective contraception during ADCETRIS treatment and for at least 6
months after the final dose of ADCETRIS.

Advise patients to report pregnancy immediately and avoid breastfeeding
while receiving ADCETRIS.

For additional Important Safety Information, including BOXED WARNING,
please see the full Prescribing Information for ADCETRIS at www.seattlegenetics.com
or http://www.adcetris.com.

Forward-Looking Statements

Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the potential
utilization of ADCETRIS (brentuximab vedotin) for patients with
previously untreated Stage IV classical Hodgkin lymphoma and the
possibility that the supplemental New Drug Submission for ADCETRIS in
combination with chemotherapy in frontline PTCL could be approved, in
each case in Canada. Actual results or developments may differ
materially from those projected or implied in these forward-looking
statements due to factors such as utilization and adoption of the
approved treatment regimen by prescribing physicians, competitive
conditions including the availability of alternative treatment regimens,
the availability and extent of reimbursement, the risk of adverse
events, and adverse regulatory action. More information about the risks
and uncertainties faced by Seattle Genetics is contained under the
caption “Risk Factors” included in the company’s Quarterly Report on
Form 10-Q for the quarter ended March 31, 2019 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.