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Sunday, December 6, 2015
Seattle Genetics Highlights Data from Denintuzumab Mafodotin (SGN-CD19A) Antibody-Drug Conjugate Program at ASH 2015
ORLANDO, Fla.--(BUSINESS WIRE)--Seattle
Genetics, Inc. Buy Lanoxin (Digoxin) without Rx (Nasdaq: SGEN) today highlighted clinical data with
denintuzumab mafodotin (SGN-CD19A; 19A) in B-cell malignancies,
including diffuse large B-cell lymphoma (DLBCL) and B-lineage acute
lymphocytic leukemia (B-ALL), presented at the 57th American
Society of Hematology (ASH) Annual Meeting and Exposition taking place
in Orlando, Florida, December 5-8, 2015. About Minipress (Prazosin) with no prescription Preclinical data from a novel
antibody-drug conjugate (ADC) program called SGN-CD19B in B-cell
malignancies will also be featured in an oral presentation. Buy Evecare () with free Rx About 85
percent of non-Hodgkin lymphomas (NHL) are B-cell lineage, and CD19 is
broadly expressed across all subtypes of B-cell malignancies. Buy Ipratop with no Rx These two
ADCs, 19A and SGN-CD19B, both target CD19 and utilize two of Seattle
Genetics’ proprietary payloads, monomethyl auristatin F (MMAF) and a
pyrrolobenzodiazepine (PBD) dimer, respectively. Buy Calan (Verapamil) with no Rx The company has
initiated the first of two planned phase 2 trials of 19A in DLBCL and
plans to advance SGN-CD19B into a phase 1 trial in 2016.
“Data presented at ASH from our 19A phase 1 trial in non-Hodgkin
lymphoma show encouraging objective response rates, particularly in
relapsed DLBCL patients, and a tolerability profile that we believe
supports further investigation as part of novel regimens. Buy Hyssop Herb online Based on these
data, we recently initiated a phase 2 trial in relapsed DLBCL, and plan
to initiate a phase 2 trial in frontline DLBCL during 2016,” said
Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice
President, Research and Development at Seattle Genetics. http://futurepharmaceuticals.wordpress.com “CD19 is an
attractive target for NHL, and there is a clear need for potent, safe
and convenient therapies that can be used to improve outcomes for
patients.”
With more than 15 years of experience and innovation, Seattle Genetics
is the leader in developing ADCs, a technology designed to harness the
targeting ability of antibodies to deliver cell-killing agents directly
to cancer cells. More than 25 ADCs in clinical development utilize
Seattle Genetics’ proprietary ADC technology.
A Phase 1 Study of Denintuzumab Mafodotin (SGN-CD19A) in
Relapsed/Refractory B-Lineage Non-Hodgkin Lymphoma (Abstract #182, oral
presentation on Sunday, December 6, 2015 at 7:45 a.m.)
Data were reported from 62 patients with relapsed or refractory NHL,
including 54 patients with DLBCL, five patients with mantle cell
lymphoma and three patients with grade 3 follicular lymphoma. Of the 62
patients, 37 patients (60 percent) were refractory to their last therapy
and 25 patients (40 percent) were relapsed. Sixteen patients (26
percent) had received a prior autologous stem cell transplant. The
median age of patients was 65 years.
The primary endpoints of the ongoing clinical trial are to estimate the
maximum tolerated dose and evaluate the safety and tolerability of 19A.
In addition, the trial is evaluating antitumor activity,
pharmacokinetics, progression-free survival and overall survival. In
this study, patients receive 19A either every three weeks or every six
weeks. Patients with stable disease or better are eligible to continue
treatment with 19A. Key findings from an oral presentation by Craig
Moskowitz, M.D. Clinical Director, Division of Hematologic
Oncology, Memorial Sloan Kettering Cancer Center, include:
The maximum tolerated dose was not exceeded after escalating to 6
milligrams per kilogram (mg/kg) every three weeks.
Of the 60 patients evaluable for response, 23 patients (38 percent)
achieved an objective response, including 14 patients (23 percent)
with a complete remission and nine patients (15 percent) with a
partial remission. Thirteen patients (22 percent) achieved stable
disease and 24 patients (40 percent) had disease progression.
Antitumor activity appeared to be higher in relapsed patients. Of the
25 relapsed patients, 15 patients (60 percent) achieved an objective
response, including 10 patients (40 percent) with a complete
remission. In the 23 relapsed patients who responded, median duration
of response was 47.1 weeks. Among all relapsed patients, median
progression-free survival was 25.1 weeks and median overall survival
was 56.7 weeks.
The most common adverse events of any grade occurring in more than 15
percent of patients were blurred vision (63 percent); dry eye (53
percent); fatigue, keratopathy and photophobia (39 percent each).
Ocular symptoms were reported in more than 70 percent of patients.
Symptoms were mostly Grade 1/2 and were managed with steroid eye drop
treatment and dose modifications. Eighty-eight percent of patients
with Grade 3 or 4 keratopathy experienced improvement and/or
resolution within a median of five weeks.
A Phase 1 Study of Denintuzumab Mafodotin (SGN-CD19A) in Adults with
Relapsed or Refractory B-Lineage Acute Leukemia (B-ALL) and Highly
Aggressive Lymphoma (Abstract #1328, poster presentation on Saturday,
December 5, 2015)
Data were reported from 72 adult patients with relapsed or refractory
B-ALL and highly aggressive lymphomas, including B-cell lymphoblastic
lymphoma (B-LBL) and Burkitt lymphoma. The median age of adult patients
was 45 years and the median number of prior systemic therapies was two,
with 20 patients (28 percent) having received a prior allogeneic stem
cell transplant.
The primary endpoints of the ongoing clinical trial are to estimate the
maximum tolerated dose and to evaluate the safety of 19A. In addition,
the trial is evaluating antitumor activity, pharmacokinetics,
progression-free survival and overall survival. In this dose-escalation
study, patients received 19A in Schedule A (40 patients) at 0.3 to 3
mg/kg weekly or Schedule B (32 patients) at 4 to 6 mg/kg every three
weeks. Key findings include:
Of the 56 B-ALL adult patients evaluable for response, six patients
(19 percent) treated weekly achieved a composite complete remission
(complete remission or complete remission with incomplete platelet or
blood recovery) and nine patients (38 percent) treated every three
weeks achieved a composite complete remission. The median duration of
response was 27 weeks. Fifty-four percent of patients across both
schedules achieved cytoreduction of greater than 50 percent.
In the ten patients with Philadelphia chromosome positive (Ph+) B-ALL,
five patients (50 percent) achieved a complete remission and one
patient (10 percent) had a partial remission. Ph+ B-ALL represents 20
to 30 percent of adult patients and carries a dismal prognosis, with
higher rates of relapse and lower overall survival.
The maximum tolerated dose was not reached in patients treated weekly
and was identified at 5 mg/kg in patients treated every three weeks.
The most common adverse events of any grade occurring in 25 percent or
more of patients treated weekly (40 patients) or every three weeks (32
patients), respectively, were nausea (63 and 41 percent), fatigue (58
and 47 percent), fever (55 and 50 percent), headache (45 and 38
percent) and anemia (43 and 22 percent).
In the study, 43 patients (60 percent) developed ocular symptoms, of
which 91 percent were Grade 1/2. These included blurred vision (39
percent), dry eye (25 percent) and photophobia (19 percent). Ocular
symptoms were managed with steroid eye drop treatment and dose
modifications. Keratopathy was observed in 34 patients, of whom 22
patients had Grade 3/4 events. The majority of patients with Grade 3/4
events had improvement or resolution with a median time of
approximately four weeks.
The 19A phase 1 clinical trials are ongoing. Separately, a randomized
phase 2 trial has recently initiated evaluating 19A in combination with
R-ICE chemotherapy for second-line DLBCL. In addition, a phase 2
clinical trial in frontline DLBCL is planned to begin in 2016. More
information about the 19A clinical trials, including enrolling centers,
is available by visiting .clinicaltrials.gov.
SGN-CD19B, a Pyrrolobenzodiazepine (PBD)-Based Anti-CD19 Drug
Conjugate, Demonstrates Potent Preclinical Activity Against B-Cell
Malignancies (Abstract #594, oral presentation on Monday, December 7,
2015 at 11:45 a.m.)
A preclinical analysis evaluated the activity of SGN-CD19B, a new ADC
consisting of an anti-CD19 antibody attached to a highly potent DNA
binding agent called a PBD dimer, in multiple B-cell malignancy models.
Data to be presented in an oral session demonstrate that SGN-CD19B
exhibits antitumor activity against a broad panel of CD19-expressing
B-cell malignancies, inducing durable tumor regressions and improved
survival in multiple preclinical models of NHL and B-ALL. Based on these
data, a phase 1 clinical trial evaluating SGN-CD19B in NHL is planned to
start in 2016.
About Denintuzumab Mafodotin (SGN-CD19A)
Denintuzumab mafodotin (SGN-CD19A; 19A) is an ADC targeting CD19, a
protein expressed broadly on B-cell malignancies. 19A is comprised of an
anti-CD19 monoclonal antibody linked to a synthetic cell-killing agent,
monomethyl auristatin F (MMAF). The ADC is designed to be stable in the
bloodstream, and to release its cytotoxic agent upon internalization
into CD19-expressing tumor cells. This approach is intended to spare
non-targeted cells and thus reduce many of the toxic effects of
traditional chemotherapy while enhancing the antitumor activity.
About Non-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 NHL. NHL is further categorized into indolent (low-grade)
or aggressive, including DLBCL. DLBCL is the most common type of NHL.
According to the American Cancer Society, more than 71,000 cases of NHL
were to be diagnosed in the United States during 2015 and more than
19,000 people would die from the disease.
About Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia, also called acute lymphocytic leukemia or
ALL, is an aggressive type of cancer of the bone marrow and blood that
progresses rapidly without treatment. In ALL, lymphoblasts, which are
malignant, immature white blood cells, multiply and crowd out normal
cells in the bone marrow. ALL is the most common type of cancer in
children. According to the American Cancer Society, more than 6,000
people will be diagnosed with ALL during 2015 and more than 1,400 would
die from the disease.
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 more
than 55 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 a robust pipeline of clinical-stage
programs, including vadastuximab talirine (SGN-CD33A; 33A), denintuzumab
mafodotin (SGN-CD19A; 19A), SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME 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 .seattlegenetics.com.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to our planned clinical
trials and the therapeutic potential of denintuzumab mafodotin
(SGN-CD19A; 19A) and SGN-CD19B. 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 the inability to show sufficient activity in the clinical trials
and risk of adverse events as denintuzumab mafodotin and SGN-CD19B
advance in clinical trials even after promising results in earlier
trials. In addition, as our other drug candidates or those of our
collaborators advance in clinical trials, adverse events and or
regulatory actions may occur which affect the future development of
those drug candidates and possibly other compounds using similar
technology. 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
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.
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