-- Phase 1/2 Multi-Center Clinical Trial to
Begin Enrolling in Q4 2019 --
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.
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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.”
“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
Statement
This 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.
- 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
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version on businesswire.com: https://www.businesswire.com/news/home/20190531005070/en/
Kite, A Gilead Company, Contacts:Sung Lee,
Investors(650) 524-7792
Shant 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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