- ACTIV-5/BET-B trial amended in the context of Humanigen’s
positive Phase 3 lenzilumab LIVE-AIR study
- Primary endpoint focuses on survival without ventilation by day
28 in patients with baseline C-reactive protein (CRP) levels less
than 150 mg/L
- Study modification may enable Humanigen to use ACTIV-5/BET-B as
a confirmatory study to support a future Biologics License
Application (BLA)
- Approximately half of the 400 patients are already enrolled in
ACTIV-5/BET-B
Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”), a clinical-stage
biopharmaceutical company developing a first-in-class GM-CSF
neutralizing antibody to prevent and treat an immune hyper-response
called ‘cytokine storm’ across multiple therapeutic indications,
has announced that the NIH has advanced the ACTIV-5/BET-B study to
a Phase 2/3 study and modified the primary endpoint to survival
without ventilation (“SWOV”), the same endpoint used in the Phase 3
LIVE-AIR study.
The amended ACTIV-5/BET-B study now includes 400 patients
overall. Up to sixty US sites will be participating in the study.
Humanigen is providing lenzilumab and assisting the NIH to achieve
the timely completion of the study. NIH is sponsoring and funding
this study.
“We appreciate the close collaboration with NIH on this
important study,” said Adrian Kilcoyne, MD, Chief Medical Officer,
Humanigen. “The ACTIV-5/BET-B study design has been adapted to
align with the design of LIVE-AIR and may help support a future BLA
for lenzilumab.”
“Sharing the same endpoint as the LIVE-AIR study, the
ACTIV-5/BET-B study reinforces the potential for lenzilumab to
treat hospitalized COVID-19 patients,” said Vincent Marconi, MD,
Professor of Medicine at Emory University School of Medicine. “At
Emory University, a key center in both the LIVE-AIR and
ACTIV-5/BET-B studies, we believe these trials can identify the
optimal patient population for lenzilumab. LIVE-AIR showed us that
COVID-19 patients who at baseline had a CRP of less than 150 mg/L
and are under 85 years of age had the greatest response to
lenzilumab. Using CRP as a biomarker to identify COVID-19 patients
at risk for disease progression, in whom lenzilumab treatment can
be initiated prior to full blown cytokine storm, would be
lifesaving.”
“ACTIV-5/BET-B may provide prospective validation for lenzilumab
in the treatment of COVID-19,” said Cameron Durrant, MD, Chief
Executive Officer, Humanigen. “We believe ACTIV-5/BET-B, along with
LIVE-AIR, will provide the sufficient size and statistical power
typically required for a BLA to be submitted to FDA.”
About ACTIV-5/BET-B
The Accelerating Covid-19 Therapeutic Interventions and Vaccines
(ACTIV) is a National Institutes of Health (NIH) directed
public-private partnership to develop a coordinated research
strategy for prioritizing and speeding development of the most
promising treatments and vaccines.1 ACTIV is led by a working group
of senior scientists representing government, industry, non-profit,
philanthropic, and academic organizations and is pursuing five
fast-track focus areas most ripe for opportunity, one of which is
accelerating clinical testing of the most promising vaccines and
treatments. Within this focus area ACTIV-5 (Big Effect Trial, BET)
is a series of randomized, double-blind, placebo-controlled trials
using common assessments and endpoints to evaluate whether certain
therapies, approved or investigational, show promise against
COVID-19.
Within ACTIV-5, lenzilumab is the first and only anti-human
GM-CSF treatment to be tested in ACTIV-5 as a concomitant therapy
with remdesivir compared with remdesivir alone. Lenzilumab was
selected from among 400 compounds that were considered for
investigation in ACTIV.2 The study began in October 2020 and was
comprised of 200 adult hospitalized patients who need medical care
for COVID-19 pneumonia and randomized (1:1) to the treatment
groups.2 Patients receive a loading dose of 200-mg intravenous (IV)
remdesivir on day 1 followed by a 100-mg once-daily IV maintenance
dose up to a 10-day total course while hospitalized. Lenzilumab (or
placebo) is administered at 600-mg IV lenzilumab infusion every 8
hours starting on Day 1 for a total of 3 doses.2 The original
primary efficacy outcome was change in clinical status on an
8-point ordinal scale at Day 8 from the NIH-sponsored Adaptive
COVID-19 Treatment Trial (ACTT, NCT 04280705).3,4
Lenzilumab Clinical Evidence Supporting Modification of
ACTIV-5/BET-B
Lenzilumab achieved the primary endpoint of the Phase 3 LIVE-AIR
trial with a 1.54-fold relative improvement in the likelihood of
SWOV compared to placebo. Lenzilumab also improved the relative
likelihood of SWOV by 1.92-fold in the pre-specified subgroup of
subjects who received both corticosteroids and remdesivir as well
as a 3-fold improvement in the likelihood of SWOV in patients with
a baseline CRP<150 mg/L and less than 85 years of age. In these
patients, a 2.2-fold improvement in the likelihood of survival was
observed with lenzilumab. No serious adverse events were attributed
to lenzilumab, and the overall safety profile was comparable to
placebo.
The LIVE-AIR, Phase 3 Study was a randomized, double-blind,
placebo-controlled, multi-center Phase 3 trial for the treatment
and prevention of serious and potentially fatal outcomes in
patients who were hospitalized with COVID-19 pneumonia. The primary
objective was to assess whether lenzilumab, in addition to other
treatments, which included dexamethasone (or other steroids) and/or
remdesivir, could alleviate the immune-mediated cytokine release
syndrome (CRS) and improve SWOV. SWOV is a composite endpoint of
time to death and time to IMV, which is a robust measure that is
less prone to favor a treatment with discordant effects on survival
or days free of ventilation.1
The LIVE-AIR study enrolled 520 patients in 29 sites in the US
and Brazil who were at least 18 years of age; experienced blood
oxygen saturation (SpO2) of less than or equal to 94%; or required
low-flow supplemental oxygen, or high-flow oxygen support, or
non-invasive positive pressure ventilation (NIPPV); and were
hospitalized but did not require IMV. Following enrollment,
subjects were randomized to receive three infusions of either
lenzilumab or placebo, each infusion separated by eight hours over
a 24-hour period with other treatments. The primary endpoint was
the difference between lenzilumab treatment and placebo treatment
in SWOV through 28 days following treatment. Key secondary
endpoints, also measured through 28 days, included ventilator-free
days, duration of ICU stay, incidence of IMV, extracorporeal
membrane oxygenation (ECMO), and/or death, time to death, all-cause
mortality, and time to recovery. LIVE-AIR results have been
submitted for potential publication in a peer-reviewed journal.
About Lenzilumab
Lenzilumab is a proprietary Humaneered® (“Humaneered”)
first-in-class monoclonal antibody that has been proven to
neutralize GM-CSF, a cytokine of critical importance in the
hyperinflammatory cascade, sometimes referred to as cytokine
release syndrome (“CRS”) or cytokine storm (CS), associated with
COVID-19 and other indications. Lenzilumab binds to and neutralizes
GM-CSF, consequently improving outcomes for hypoxic patients
hospitalized with COVID-19. Humanigen believes that its GM-CSF
neutralization has the potential to reduce the hyper-inflammatory
cascade known as cytokine release syndrome common to chimeric
antigen receptor T-cell (CAR-T) therapy and acute Graft versus Host
Disease (aGvHD).
In CAR-T, lenzilumab successfully achieved pre-specified primary
endpoint at the recommended dose in a Phase 2 study with Yescarta
in which the overall response rate was 100% and no patient
experienced severe cytokine release syndrome or severe
neurotoxicity. Based on these results, Humanigen plans to test
lenzilumab in a randomized, multicenter, potentially
registrational, Phase 2 study to evaluate its efficacy and safety
when combined with all commercially available CD19 CAR-T therapies
in DLBCL. Lenzilumab will also be tested to assess its ability
prevent and/or treat aGvHD in patients undergoing allogeneic
hematopoietic stem cell transplantation (HSCT).
About Humanigen
Humanigen, Inc. is developing its portfolio of clinical and
pre-clinical therapies for the treatment of inflammation and
immuno-oncology. Humanigen’s immediate focus is to prevent or
minimize cytokine release syndrome that precedes severe lung
dysfunction in hospitalized and hypoxic patients with COVID-19
pneumonia. Humanigen has requested Emergency Use Authorization for
this indication and is submitting lenzilumab to the Medicines and
Health Regulatory Agency in the United Kingdom under an expedited
rolling review seeking Marketing Authorization. Humanigen is also
exploring the effectiveness of lenzilumab in other inflammatory
conditions such as aGvHD and cytokine release syndrome associated
with CAR-T. For more information, visit www.humanigen.com and
follow Humanigen on LinkedIn, Twitter, and Facebook.
Forward-Looking Statements
All statements other than statements of historical facts
contained in this press release are 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 request for and receipt of an
Emergency Use Authorization from FDA for lenzilumab in COVID-19;
our request and receipt of Marketing Authorization or Conditional
Marketing Authorization for lenzilumab in COVID-19 by the MHRA; and
our other plans relating to lenzilumab to further development of
lenzilumab.
Forward-looking statements are subject to a number of risks and
uncertainties including, but not limited to, the risks inherent in
our lack of profitability and need for additional capital to grow
our business; our dependence on partners to further the development
of our product candidates; the uncertainties inherent in the
development, attainment of the requisite regulatory authorizations
and approvals 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 of our
latest annual and quarterly reports and other filings with the
SEC.
All forward-looking statements are expressly qualified in their
entirety by this cautionary notice. You should not rely upon any
forward-looking statements as predictions of future events. We
undertake no obligation to revise or update any forward-looking
statements made in this presentation to reflect events or
circumstances after the date hereof, to reflect new information or
the occurrence of unanticipated events, to update the reasons why
actual results could differ materially from those anticipated in
the forward-looking statements, in each case, except as required by
law.
References
- National Institutes of Health. (n.d.). "ACCELERATING COVID-19
THERAPEUTIC INTERVENTIONS AND VACCINES (ACTIV)."
https://www.nih.gov/research-training/medical-research-initiatives/activ.
- Collins, D. F. (2021, February 16). ACTIV Update: Making major
strides in covid-19 Therapeutic Development. NIH Director's Blog.
https://directorsblog.nih.gov/2021/02/16/activ-update-making-major-strides-in-covid-19-therapeutic-development/
(accessed July 30, 2021)
- The National Library of Medicine – ClinicalTrials.gov (2021,
July 9). ACTIV-5 / Big Effect Trial (BET-B) for the Treatment of
COVID-19. https://www.clinicaltrials.gov/ct2/show/NCT04583969.
- Beigel J.H., Tomashek K.M., Dodd L.E., et al. (2020).
Remdesivir for the Treatment of COVID-19 — Final Report. New
England Journal of Medicine, 383(19), 1813–1826.
https://doi.org/10.1056/nejmoa2007764.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210730005439/en/
Humanigen Media Grace Catlett RXMD Gcatlett@rxmedyn.com
516-318-8563 Humanigen Investor Relations Ken Trbovich
Humanigen trbo@humanigen.com 650-410-3206
Humanigen (NASDAQ:HGEN)
Historical Stock Chart
From Mar 2024 to Apr 2024
Humanigen (NASDAQ:HGEN)
Historical Stock Chart
From Apr 2023 to Apr 2024