Kite, a Gilead Company (Nasdaq: GILD) and Humanigen, Inc., (HGEN)
announced today the formation of a clinical collaboration to
conduct a Phase 1/2 study of lenzilumab, an investigational
anti-GM-CSF monoclonal antibody, with Yescarta® (axicabtagene
ciloleucel) in patients with relapsed or refractory diffuse large
B-cell lymphoma (DLBCL). The objective of this study is to
determine the effect of lenzilumab on the safety of Yescarta. Kite
will act as the sponsor of this study and will be responsible for
its conduct.
GM-CSF has been identified, through clinical
correlative analysis and preclinical modeling, as a potential key
signal in the inflammatory cascade triggering toxicities associated
with chimeric antigen receptor T (CAR T) cell
therapy.1 Toxicities associated with CAR T therapy include
neurologic toxicity and cytokine release syndrome (CRS). Emerging
pre-clinical evidence suggests that lenzilumab inhibition of GM-CSF
may have the potential to disrupt CAR T cell mediated inflammation
without disrupting CAR T cell anti-tumor efficacy.
“CAR T therapy represents a significant advance
in the way relapsed or refractory large B-cell lymphoma is
treated,” said John McHutchison, AO, MD, Chief Scientific Officer,
Head of Research and Development, Gilead. “As leaders in cell
therapy, we are committed to pursuing a number of clinical and
preclinical strategies aimed at further improving the efficacy and
safety of CAR T therapy. We look forward to this clinical
collaboration with Humanigen and to evaluating the combination of
lenzilumab and Yescarta in our clinical trial.”
1 Sterner, R., Sakemura, R., Cox, M., Yang, N.,
Khadka, R., Forsman, C.,… Kenderian, S. (2019). GM-CSF inhibition
reduces cytokine release syndrome and neuroinflammation but
enhances CAR-T cell function in xenografts. Blood : the
official journal of the American Society of Hematology,
133:697-709. doi: https://doi.org/10.1182/blood-2018-10-881722
“Humanigen has pioneered the approach to
neutralizing GM-CSF to improve CAR T,” said Cameron Durrant, MD,
Chief Executive Officer, Humanigen. “This collaboration with Kite
will help validate the work Humanigen has done in understanding the
pathophysiology of the inflammatory cascade as well as the
potential role GM-CSF plays in influencing CAR T cell treatment
outcomes.”
Yescarta was the first CAR T cell therapy to be
approved by the U.S. Food and Drug Administration (FDA) for the
treatment of adult patients with relapsed or refractory large
B-cell lymphoma after two or more lines of systemic therapy,
including DLBCL not otherwise specified, primary mediastinal large
B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising
from follicular lymphoma. Yescarta is not indicated for the
treatment of patients with primary central nervous system lymphoma.
The Yescarta U.S. Prescribing Information has a BOXED WARNING for
the risks of cytokine release syndrome and neurologic toxicities;
see below for Important Safety Information.
Lenzilumab, alone or in combination with other
therapies such as Yescarta, is investigational and has not been
approved by the FDA or any regulatory authority for any uses.
Efficacy and safety have not yet been established.
Stifel, Nicolaus & Company, Incorporated
acted as exclusive financial advisor to Humanigen in this
transaction.
U.S. Important Safety Information for
Yescarta BOXED WARNING: CYTOKINE RELEASE
SYNDROME AND NEUROLOGIC TOXICITIES
- Cytokine Release Syndrome (CRS), including fatal or
life-threatening reactions, occurred in patients receiving
Yescarta. Do not administer Yescarta to patients with active
infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
- Neurologic toxicities, including fatal or
life-threatening reactions, occurred in patients receiving
Yescarta, including concurrently with CRS or after CRS resolution.
Monitor for neurologic toxicities after treatment with Yescarta.
Provide supportive care and/or corticosteroids as
needed.
- Yescarta is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
Yescarta REMS.
CYTOKINE RELEASE SYNDROME
(CRS): CRS occurred in 94% of patients,
including 13% with ≥ Grade 3. Among patients who died after
receiving Yescarta, 4 had ongoing CRS at death. The median time to
onset was 2 days (range: 1-12 days) and median duration was 7 days
(range: 2-58 days). Key manifestations include fever (78%),
hypotension (41%), tachycardia (28%), hypoxia (22%), and chills
(20%). Serious events that may be associated with CRS include
cardiac arrhythmias (including atrial fibrillation and ventricular
tachycardia), cardiac arrest, cardiac failure, renal insufficiency,
capillary leak syndrome, hypotension, hypoxia, and hemophagocytic
lymphohistiocytosis/macrophage activation syndrome. Ensure that 2
doses of tocilizumab are available prior to infusion of Yescarta.
Monitor patients at least daily for 7 days at the certified
healthcare facility following infusion for signs and symptoms of
CRS. Monitor patients for signs or symptoms of CRS for 4 weeks
after infusion. Counsel patients to seek immediate medical
attention should signs or symptoms of CRS occur at any time. At the
first sign of CRS, institute treatment with supportive care,
tocilizumab or tocilizumab and corticosteroids as indicated.
NEUROLOGIC TOXICITIES:
Neurologic toxicities occurred in 87% of patients. Ninety-eight
percent of all neurologic toxicities occurred within the first 8
weeks, with a median time to onset of 4 days (range: 1-43 days) and
a median duration of 17 days. Grade 3 or higher occurred in 31% of
patients. The most common neurologic toxicities included
encephalopathy (57%), headache (44%), tremor (31%), dizziness
(21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety
(9%). Prolonged encephalopathy lasting up to 173 days was noted.
Serious events including leukoencephalopathy and seizures occurred
with Yescarta. Fatal and serious cases of cerebral edema have
occurred in patients treated with Yescarta. Monitor patients
at least daily for 7 days at the certified healthcare facility
following infusion for signs and symptoms of neurologic toxicities.
Monitor patients for signs or symptoms of neurologic toxicities for
4 weeks after infusion and treat promptly.
YESCARTA REMS: Because of the
risk of CRS and neurologic toxicities, Yescarta is available only
through a restricted program under a Risk Evaluation and Mitigation
Strategy (REMS) called the Yescarta REMS. The required components
of the Yescarta REMS are: Healthcare facilities that dispense and
administer Yescarta must be enrolled and comply with the REMS
requirements. Certified healthcare facilities must have on-site,
immediate access to tocilizumab, and ensure that a minimum of 2
doses of tocilizumab are available for each patient for infusion
within 2 hours after Yescarta infusion, if needed for treatment of
CRS. Certified healthcare facilities must ensure that healthcare
providers who prescribe, dispense or administer Yescarta are
trained about the management of CRS and neurologic toxicities.
Further information is available at www.YESCARTAREMS.com or
1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS:
Allergic reactions may occur. Serious hypersensitivity reactions
including anaphylaxis may be due to dimethyl sulfoxide (DMSO) or
residual gentamicin in Yescarta.
SERIOUS
INFECTIONS: Severe or life-threatening
infections occurred. Infections (all grades) occurred in 38% of
patients, and in 23% with ≥ Grade 3. Grade 3 or higher infections
with an unspecified pathogen occurred in 16% of patients, bacterial
infections in 9%, and viral infections in 4%. Yescarta should not
be administered to patients with clinically significant active
systemic infections. Monitor patients for signs and symptoms of
infection before and after Yescarta infusion and treat
appropriately. Administer prophylactic anti-microbials according to
local guidelines. Febrile neutropenia was observed in 36% of
patients and may be concurrent with CRS. In the event of febrile
neutropenia, evaluate for infection and manage with broad spectrum
antibiotics, fluids and other supportive care as medically
indicated. Hepatitis B virus (HBV) reactivation, in some cases
resulting in fulminant hepatitis, hepatic failure and death, can
occur in patients treated with drugs directed against B cells.
Perform screening for HBV, HCV, and HIV in accordance with clinical
guidelines before collection of cells for manufacturing.
PROLONGED
CYTOPENIAS: Patients may exhibit
cytopenias for several weeks following lymphodepleting chemotherapy
and Yescarta infusion. Grade 3 or higher cytopenias not resolved by
Day 30 following Yescarta infusion occurred in 28% of patients and
included thrombocytopenia (18%), neutropenia (15%), and anemia
(3%). Monitor blood counts after Yescarta infusion.
HYPOGAMMAGLOBULINEMIA: B-cell
aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia
occurred in 15% of patients. Monitor immunoglobulin levels after
treatment and manage using infection precautions, antibiotic
prophylaxis and immunoglobulin replacement. The safety of
immunization with live viral vaccines during or following Yescarta
treatment has not been studied. Vaccination with live virus
vaccines is not recommended for at least 6 weeks prior to the start
of lymphodepleting chemotherapy, during Yescarta treatment, and
until immune recovery following treatment.
SECONDARY
MALIGNANCIES: Patients may develop
secondary malignancies. Monitor life-long for secondary
malignancies. In the event that a secondary malignancy occurs,
contact Kite at 1-844-454-KITE (5483) to obtain instructions on
patient samples to collect for testing.
EFFECTS ON ABILITY TO DRIVE AND USE
MACHINES: Due to the potential for
neurologic events, including altered mental status or seizures,
patients are at risk for altered or decreased consciousness or
coordination in the 8 weeks following Yescarta infusion. Advise
patients to refrain from driving and engaging in hazardous
occupations or activities, such as operating heavy or potentially
dangerous machinery, during this initial period.
ADVERSE
REACTIONS: The most common adverse
reactions (incidence ≥ 20%) include CRS, fever, hypotension,
encephalopathy, tachycardia, fatigue, headache, decreased appetite,
chills, diarrhea, febrile neutropenia, infections-pathogen
unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness,
constipation, and cardiac arrhythmias.
About Kite Kite, a Gilead
Company, is a biopharmaceutical company based in Santa Monica,
California. Kite is engaged in the development of innovative cancer
immunotherapies. The company is focused on chimeric antigen
receptor and T cell receptor engineered cell therapies. For more
information on Kite, please visit www.kitepharma.com.
About Gilead Sciences Gilead
Sciences, Inc. is a research-based biopharmaceutical company
that discovers, develops and commercializes innovative medicines in
areas of unmet medical need. The company strives to transform and
simplify care for people with life-threatening illnesses around the
world. Gilead has operations in more than 35 countries worldwide,
with headquarters in Foster City, California. For more
information on Gilead Sciences, please visit the company’s website
at www.gilead.com.
About Humanigen, Inc.
Humanigen, Inc. is developing its portfolio of Humaneered®
monoclonal antibodies to address cutting-edge CAR-T optimization
and the need for new oncology drugs that provide safer, better, and
more effective cancer therapies. Derived from the company’s
Humaneered® platform, lenzilumab, ifabotuzumab, and HGEN005 are
monoclonal antibodies with first-in-class mechanisms. Lenzilumab,
which neutralizes human GM-CSF, is in development as a potential
biologic therapy to make CAR-T therapy safer and more effective, as
well as a potential treatment for hematologic cancers.
Ifabotuzumab, which targets the Eph type-A receptor 3 (EphA3), is
being explored as a potential treatment for a range of solid
tumors, as well as a backbone for a novel CAR-T construct, and a
bispecific antibody platform. HGEN005 which selectively targets the
eosinophil receptor EMR1 is being explored as a potential treatment
for a range of eosinophilic diseases including eosinophilic
leukemia both as an optimized naked antibody and as the backbone
for a novel CAR-T construct. For more information,
visit www.humanigen.com.
Gilead Forward-Looking
Statement This press release includes forward-looking
statements, within the meaning of the Private Securities Litigation
Reform Act of 1995 that are subject to risks, uncertainties and
other factors, including Kite’s ability to complete the Phase 1/2
study of Yescarta in combination with lenzilumab in patients with
relapsed or refractory DLBCL in the currently anticipated
timelines, or at all. In addition, there is the possibility of
unfavorable results from clinical trials involving this
combination, Yescarta and other investigational CAR T therapies.
Further, it is possible that the parties may make a strategic
decision to discontinue development of the investigational
combination of Yescarta and lenzilumab. All statements other than
statements of historical fact are statements that could be deemed
forward-looking statements. These risks, uncertainties and other
factors could cause actual results to differ materially from those
referred to in the forward-looking statements. The reader is
cautioned not to rely on these forward-looking statements. These
and other risks are described in detail in Gilead’s Quarterly
Report on Form 10-Q for the quarter ended March 31, 2019, as filed
with the U.S. Securities and Exchange Commission. All
forward-looking statements are based on information currently
available to Gilead and Kite, and Gilead and Kite assume no
obligation to update any such forward-looking statements.
Humanigen Forward-Looking
StatementThis release contains forward-looking statements.
Forward-looking statements reflect management's current knowledge,
assumptions, judgment and expectations regarding future performance
or events. Although management believes that the expectations
reflected in such statements are reasonable, they give no assurance
that such expectations will prove to be correct and you should be
aware that actual events or results may differ materially from
those contained in the forward-looking statements. Words such as
"will," "expect," "intend," "plan," "potential," "possible,"
"goals," "accelerate," "continue," and similar expressions identify
forward-looking statements, including, without limitation,
statements regarding our expectations for future development of
lenzilumab to help CAR-T therapy reach its full potential.
Forward-looking statements are subject to a number of risks and
uncertainties including, but not limited to, the risks inherent in
Black Horse Capital and its affiliates owning more than 50% of our
outstanding common stock, including their ability to control the
company; our lack of profitability and need for additional capital
to operate our business as a going concern; the uncertainties
inherent in the development and launch of any new pharmaceutical
product; the outcome of pending or future litigation; and the
various risks and uncertainties described in the "Risk Factors"
sections and elsewhere in the Company's periodic and other filings
with the Securities and Exchange Commission.
All forward-looking statements are expressly
qualified in their entirety by this cautionary notice. You should
not place undue reliance on any forward-looking statements, which
speak only as of the date of this release. We undertake no
obligation to revise or update any forward-looking statements made
in this press release to reflect events or circumstances after the
date hereof or to reflect new information or the occurrence of
unanticipated events, except as required by law.
U.S. Prescribing Information for Yescarta,
including BOXED WARNING, is available at
www.kitepharma.com and www.gilead.com.
Yescarta is a registered trademark of Gilead
Sciences, Inc., or its related companies.
Kite, A Gilead Company,
Contacts:Sung Lee, Investors(650)
524-7792Shant Salakian,
Media
(424) 384-1841
Humanigen Contacts:Al Palombo, Investors (650)
243-3181ir@humanigen.com Chris Bowe, Media(646)
662-7628cbowe@humanigen.com
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