NEW YORK, Feb. 17, 2021 /PRNewswire/ -- Immunic,
Inc. (Nasdaq: IMUX), a clinical-stage
biopharmaceutical company developing a pipeline of selective oral
immunology therapies aimed at treating chronic inflammatory and
autoimmune diseases, today announced that its lead asset, IMU-838,
the company's selective oral DHODH inhibitor, has shown evidence of
clinical activity in hospitalized patients with moderate
coronavirus disease 2019 (COVID-19). This planned main analysis of
the company's phase 2 CALVID-1 trial is based on data from 204
randomized patients and includes top-line clinical efficacy,
safety, disease marker, and virology data. Although no formal
statistical analysis was pre-specified for this main analysis,
endpoints have been analyzed descriptively. A final analysis of the
complete randomized patient population of 223, which will comprise
data on all endpoints, including subgroup and sensitivity analyses,
is expected to be available in the second quarter of 2021.
The primary endpoint of the randomized, placebo-controlled,
double-blind trial was defined as the proportion of patients
without any need for invasive ventilation through day 28. In
contrast to the relatively high rates of ventilation reported in
the first COVID-19 wave in early 2020, the CALVID-1 trial found an
actual rate of less than 1% of invasive ventilation for
hospitalized patients with moderate COVID-19. This very low event
rate, consistent with the findings of many recent third-party
trials in COVID-19, prevented the primary endpoint from being
evaluable.
Regarding the key secondary endpoints, the trial was designed to
investigate IMU-838's ability to reduce the probability of major
complications for COVID-19 patients, such as 28-day mortality,
survival without respiratory failure, and probability of use of
intensive care unit (ICU) treatment. Similar to the low ventilation
rates discussed above, the trial found a rate of less than 2% for
28-day mortality, balanced between the two arms, and less than 4.5%
of patients required an ICU stay. Based on the very low
complication rates in this trial and due to the known variability
of the disease course, Immunic believes that the evaluation of
these key secondary endpoints is also not feasible.
Despite the low mortality and invasive ventilation rates
observed in this trial, clinical activity of IMU-838 was confirmed
based on the assessment of multiple secondary clinical
endpoints:
Time to clinical recovery[1]: The proportion
of patients reaching clinical recovery at day 7 was 18.5% (N=15) in
IMU-838 treated patients, compared with only 12.8% (N=10) in the
placebo arm. At day 28, 71.3% (N=57) of the IMU-838 treated
patients had recovered compared with only 66.7% (N=58) in the
placebo arm (FAS[2]).
Time to clinical improvement[3]: Time to
clinical improvement was found to be shorter in the IMU-838 treatment arm, as
compared to placebo, and the incremental benefit increased over
time (mFAS[4]).
- The proportion of patients reaching clinical improvement (as
assessed by the investigators) at day 14 was 42.7% (N=38) in
IMU-838 treated patients compared with only 38.5% (N=35) in the
placebo arm (FAS). At day 28, the numbers were 90.9% (N=90) and
87.4% (N=90), respectively. The relative proportion of patients not
improving was 6.8% greater in the placebo arm than the IMU-838
treatment arm at 14 days, and 27.7% greater at 28 days.
- Following day 14[5], patients treated with IMU-838
experienced a numerically higher probability of clinical
improvement (centrally calculated) compared with those on placebo.
For instance, the 75% probability[5] to reach clinical
improvement was accelerated by 2.9 days in IMU-838 treated
patients, as compared to placebo (mFAS).
- The third patient quartile[5] for duration of
hospitalization (75% of patients have a shorter hospitalization
duration and 25% have a longer duration of hospitalization) was
shortened by 3.4 days in IMU-838 treated patients, as compared to
placebo (mFAS). Meanwhile, Immunic believes that trial design
issues and regulatory requirements may obscure any potential
differences in the median (50th percentile)
itself[5].
- Clinical improvement (centrally calculated) was observed to be
better when IMU-838 was used early in the COVID-19 disease course
(within the first 8 days after onset of symptoms, mFAS).
- Initial data from a post hoc analysis of what is called "Long
COVID" symptoms, the frequently remaining symptoms of COVID-19
after elimination of the virus, indicated that IMU-838 may have the
potential to contribute to the prevention of long-term
fatigue.
|
mFAS
Population[4] (Days)
|
Probability
of
Clinical
Improvement
(Centrally Calculated)
|
IMU-838
|
Placebo
|
Difference in
Favor of IMU-838
|
50%
|
13.9
|
13.9
|
0.0
|
75%
|
15.0
|
17.9
|
2.9
|
90%
|
18.9
|
26.8
|
7.9
|
Table: IMU-838 Shows Acceleration of Time to Clinical
Improvement
High-risk patients and patients aged over 65 years experienced a
more substantial treatment benefit from IMU-838 than in the general
patient population:
- The 75% probability[5] to reach clinical improvement
(based on investigator assessment) was accelerated by 3.8 days in
IMU-838 treated high-risk patients[6], as compared to
placebo (FAS).
- The 75% probability[5] to reach clinical improvement
(based on investigator assessment) was accelerated by 4.8 days in
IMU-838 treated elderly patients (65 years or older), as compared
to placebo (FAS).
- In the group of elderly patients (65 years or older), IMU-838
contributed to a faster improvement in WHO scores by at least two
points, as compared to placebo (mFAS). At day 14, 36.4% (N=8/22) of
the elderly patients reached a WHO score improvement by two points
following treatment of IMU-838, whereas only 22.2% (N=4/18) of the
elderly patients reached such improvement following placebo
treatment at day 14.
Viral burden as well as biochemical inflammation and disease
markers:
- An anti-viral effect of IMU-838 on SARS-CoV-2 was observed by
viral titers at the end of the treatment period (day 14) and at the
end of the study (day 28).
- An anti-inflammatory effect of IMU-838 was observed based on a
more effective reduction of C-reactive protein (CRP), a well-known
marker for inflammation in the blood, in IMU-838 treated patients,
as compared to placebo.
- A more effective reduction of D-dimer, a well-known prognostic
disease marker for COVID-19, was observed in IMU-838 treated
patients, as compared to placebo.
IMU-838 was found to be safe and well-tolerated in hospitalized
patients with moderate COVID-19. No general safety signals
regarding new or more severe adverse events were observed for
IMU-838 in this patient population, as compared to placebo. In
addition, IMU-838's rate of serious adverse events and adverse
events leading to treatment discontinuation was not increased, as
compared to placebo. The trial also found fewer COVID-19 related
adverse events with increased intensity in IMU-838 treated patients
(7.1%), as compared to placebo (12.6%) and IMU-838 did not
intensify any hematological effects of COVID-19. In addition,
IMU-838 did not increase the rate of infections and infestations as
well as the rate of liver events in patients with COVID-19, as
compared to placebo.
"I am truly excited to report that our CALVID-1 trial showed
clinical activity of IMU-838 in hospitalized patients with moderate
COVID-19 and also reproduced in this patient population the drug's
already established favorable safety and tolerability profile,"
stated Daniel Vitt, Ph.D., Chief
Executive Officer and President of Immunic. "The reductions in
hospitalization and clinical recovery times observed thus far in
our CALVID-1 trial are clinically meaningful, and particularly
interesting in the high-risk and elderly populations. In addition,
we have seen effects on preventing long-term COVID-19 symptoms
which suggest that IMU-838 could be a promising new therapeutic
intervention that could provide meaningful clinical benefit. I
strongly believe that this trial underlines the potential of
IMU-838 to be a convenient, safe and well-tolerated oral treatment
option for patients with moderate COVID-19 and may even pave the
way for testing IMU-838 in earlier stage COVID-19 patients in the
future. We look forward to analyzing the final data on the full 223
patient population, but we are also mindful of the rapidly changing
COVID-19 landscape for decisions on future plans. In the meantime,
we look forward to discussing the results of this main analysis as
well as the upcoming full analysis with clinical and regulatory
experts. In parallel, we plan to explore options for the further
development of IMU-838 in this indication and for funding
support."
"The Immunic team is forever indebted to the countless
physicians, nurses, study coordinators and other healthcare
personnel who participated in this trial while, at the same,
working under challenging conditions in this pandemic situation, in
order to improve lives and outcomes for patients infected with the
SARS-CoV-2 virus," added Andreas
Muehler, M.D., Chief Medical Officer of Immunic. "With
the help of our collaborators, we were able to show clinical
activity of IMU-838 in COVID-19 patients and, consistent with prior
data sets in other patient populations, administration of IMU-838
in this trial was observed to be safe and well-tolerated, thereby
providing evidence of an attractive target profile for IMU-838 as a
convenient oral treatment option in the moderate COVID-19 patient
population. The treatment effect of IMU-838 versus placebo appears
to be commensurate with that of other medications which were
successfully tested in COVID-19. Based on these promising clinical
data from the main analysis of our CALVID-1 trial, later also
complemented by the more detailed efficacy and virology data from
the full analysis of all randomized patients, we will evaluate the
way forward for IMU-838 as a potential treatment option for
COVID-19 patients."
A total of 204 patients were included in the main analysis of
the CALVID-1 trial, as per the protocol requirement of
approximately 200 patients. 202 patients received at least one dose
of study drug, of whom 99 patients received 45 mg/day of IMU-838
and 103 patients received placebo. The main analysis contains
top-line data for the treatment period until day 14 and the
follow-up period until day 28 as well as the full safety data until
day 28. Additional data will be reported after the full analysis of
all 223 randomized patients, which is expected to be available in
the second quarter of 2021. This supplemental data set will contain
full efficacy, virology, and drug trough level data, as well as the
safety follow-up until day 60.
The aim of the CALVID-1 trial was to investigate IMU-838 as an
oral treatment option for COVID-19 and to support potential use of
IMU-838 as a treatment for current and potential future viral
pandemic threats. The prospective, multicenter, randomized,
placebo-controlled, double-blind phase 2 trial was designed to
evaluate efficacy, safety and tolerability of IMU-838 in patients
with moderate COVID-19. Patients were enrolled at 20 sites in
eleven countries, including the United
States, Germany, and a
range of other European countries. Patients were randomized to
receive either 22.5 mg of IMU-838 twice daily (45 mg/day), or
placebo twice daily, for 14 consecutive days. Patients in both arms
were also eligible to receive investigator's choice of
standard-of-care therapy throughout the duration of the study.
Inclusion criteria called for hospitalized adult patients with a
confirmed SARS-CoV-2 infection fulfilling clinical status category
3 or 4, as assessed with the nine-category ordinal scale proposed
by the World Health Organization (WHO) COVID-19 Therapeutic Trial
Synopsis, as well as certain additional clinical and laboratory
criteria.
For more information on this clinical trial, please
visit: www.clinicaltrials.gov, NCT04379271.
Conference Call and Webcast Information
Immunic's management team will host a public conference call and
webcast on February 18, 2021
at 8:00 a.m. Eastern Time to discuss the data from the
main phase 2 analysis of the CALVID-1 trial of IMU-838 in
hospitalized patients with moderate COVID-19.
To participate in the conference call, dial 1-877-870-4263
(USA) or 1-412-317-0790
(International) and ask to be joined into the Immunic, Inc. call. A
live, listen-only webcast of the conference call can be accessed at
https://www.webcaster4.com/Webcast/Page/2301/39950 or on the
"Events and Presentations" section of Immunic's website at
ir.imux.com/events-and-presentations.
An archived replay of conference call and webcast will be
available approximately one hour after the completion for one year
on Immunic's website at: ir.imux.com.
[1] Time to recovery is defined as axillary temperature <=
36.6 °C, or oral temperature <= 37.2 °C, or rectal or tympanic
temperature <= 37.8 °C, and respiratory frequency <= 24
times/min without oxygen inhalation and oxygen saturation >=
98%. Clinical recovery is only assumed if it is confirmed in the
evening and at the next visit (if applicable).
[2] FAS: full analysis set: Includes all patients randomized who
received at least one dose of study drug (n=99 for IMU-838, n=103
for Placebo).
[3] Time to clinical improvement is defined as as an improvement of
at least two points on the derived nine-category ordinal WHO scale,
or live discharge from hospital without oxygen supplementation,
whichever comes first.
[4] mFAS: modified full analysis set: Patients who had positive
local virus tests during the screening period, but no positive
confirmation was possible by centralized virology laboratory
(presumably due to sampling and storage issues) at a later
timepoint, were excluded because the virus status for the WHO score
was not assessable. Thus, the mFAS analysis was used for endpoints
(such as centrally calculated WHO scores) that included data from
the central virology laboratory, whereas any endpoint that was
independent from the central virology laboratory and used local
virology results (such as WHO score based on investigator
assessment) were analyzed in the FAS population. Additionally, for
endpoints that included the variable hospitalization (such as time
to clinical improvement), the mFAS population also excluded
patients randomized in Bulgaria.
The national regulatory agency required that all patients at
Bulgarian centers be hospitalized during the entire 14-day
treatment period. Because assessment of the WHO status includes
hospitalization status, Bulgarian patients were excluded from
centralized calculations of the WHO score. Immunic believes that
this avoids the bias of mandatory hospitalization (see also
footnote 5 below) independent of COVID-19 status. For endpoints
that are independent of hospitalization duration or that are based
on the investigator assessment of need for hospitalization, the FAS
population has been reported.
[5] Although the most common presentation of data generally focuses
on the median, or 50th percentile, Immunic believes that
the third quartile/75th percentile is more appropriate
in this case. The median for the hospitalization time for both
IMU-838 and placebo arms in this trial was 14.0 days in the FAS
population, which is likely due to several factors relating to
regulatory guidance and trial design. First, the Bulgarian
regulatory agency required that all trial participants in that
country be hospitalized for the entire 14-day treatment period of
the trial, and not be discharged during that period independent of
health or viral status. Second, the trial design, on the advice of
regulatory agencies and clinical experts, included mandatory study
visits at days 6 and 14, mainly for evaluation of safety, which we
believe led investigators in many cases to wait for the completion
of these visits before discharging patients. The study results show
a large proportion of patients who discharged from hospital
immediately after these two required visits. Such behavior has
introduced an evaluation bias for all hospitalization-related
endpoints, such as central calculation of time to clinical
improvement where the hospitalization status is part of the
calculated WHO score, and may have masked treatment-related
differences between treatment groups up to day 14. To counteract
this evaluation bias, all clinical endpoints relying on
hospitalization status presented in this analysis focus on the
third quartile data, which in statistical terms represents the 25%
of patients group right after the median. For proportion of
patients between treatment groups, this correlates to the 75%
probability which is also presented here. Immunic believes that
this provides the most unbiased assessment for clinical endpoints
given the evaluation bias of hospitalization status.
[6] High-risk factors are age ≥65 years, cardiovascular disease
(including hypertension), pre-existing pulmonary disease, diabetes,
malignancy, medical conditions leading to immunodeficiency, current
or recent (within three months) immunosuppressive treatment.
About IMU-838
IMU-838 is an orally available,
next-generation selective immune modulator that inhibits the
intracellular metabolism of activated immune cells by blocking the
enzyme dihydroorotate dehydrogenase (DHODH). IMU-838 acts on
activated T and B cells while leaving other immune cells largely
unaffected and allows the immune system to stay functioning, e.g.
in fighting infections. In previous trials, IMU-838 did not show an
increased rate of infections compared to placebo. In addition,
DHODH inhibitors, such as IMU-838, are known to possess a
host-based antiviral effect, which is independent with respect to
specific virus proteins and their structure. Therefore, DHODH
inhibition may be broadly applicable against multiple viruses.
IMU-838 was successfully tested in two phase 1 clinical trials in
2017 and is currently being tested in a phase 2 trial in patients
with ulcerative colitis. In the third quarter of 2020, the company
reported positive results from its phase 2 EMPhASIS trial of
IMU-838 in relapsing-remitting multiple sclerosis, achieving both
primary and key secondary endpoints with high statistical
significance. In the first quarter of 2021, Immunic announced that
IMU-838 has shown evidence of clinical activity in its phase 2
CALVID-1 trial in hospitalized patients with moderate COVID-19.
Furthermore, Immunic's collaboration partner, the Mayo Clinic, has
started an investigator-sponsored proof-of-concept clinical trial
testing IMU-838 activity in patients with primary sclerosing
cholangitis. To date, IMU-838 has been tested in about 800
individuals and has shown an attractive pharmacokinetic, safety and
tolerability profile. IMU-838 is not yet licensed or approved in
any country.
About Immunic, Inc.
Immunic, Inc. (Nasdaq: IMUX) is a
clinical-stage biopharmaceutical company with a pipeline of
selective oral immunology therapies aimed at treating chronic
inflammatory and autoimmune diseases, including relapsing-remitting
multiple sclerosis, ulcerative colitis, Crohn's disease, and
psoriasis. Immunic is developing three small molecule products: its
lead development program, IMU-838, is a selective immune modulator
that inhibits the intracellular metabolism of activated immune
cells by blocking the enzyme DHODH and exhibits a host-based
broad-spectrum antiviral effect; IMU-935 is an inverse agonist of
RORγt; and IMU-856 targets the restoration of the intestinal
barrier function. For further information, please visit:
www.imux.com.
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains "forward-looking
statements" that involve substantial risks and uncertainties for
purposes of the safe harbor provided by the Private Securities
Litigation Reform Act of 1995. All statements, other than
statements of historical facts, included in this press release
regarding strategy, future operations, future financial position,
future revenue, projected expenses, prospects, plans and objectives
of management are forward-looking statements. Examples of such
statements include, but are not limited to, statements relating to
Immunic's three development programs and the targeted diseases; the
potential for IMU-838 to safely and effectively target diseases;
the timing of current and future clinical trials; the potential for
IMU-838 as a treatment for SARS-CoV-2 infections associated with
COVID-19 that may be supported by the company's phase 2 CALVID-1
trial data, and any clinical trials, collaborations and approvals
relating to such potential treatment; the nature, strategy and
focus of the company; and the development and commercial potential
of any product candidates of the company. Immunic may not actually
achieve the plans, carry out the intentions or meet the
expectations or projections disclosed in the forward-looking
statements and you should not place undue reliance on these
forward-looking statements. Such statements are based on
management's current expectations and involve risks and
uncertainties. Actual results and performance could differ
materially from those projected in the forward-looking statements
as a result of many factors, including, without limitation, the
COVID-19 pandemic, risks and uncertainties associated with the
ability to project future cash utilization and reserves needed for
contingent future liabilities and business operations, the
availability of sufficient resources to meet business objectives
and operational requirements, the fact that the results of earlier
studies and trials may not be predictive of future clinical trial
results, the protection and market exclusivity provided by
Immunic's intellectual property, risks related to the drug
development and the regulatory approval process and the impact of
competitive products and technological changes. A further list and
descriptions of these risks, uncertainties and other factors can be
found in the section captioned "Risk Factors," in the company's
Annual Report on Form 10-K for the fiscal year ended December 31, 2019, filed with the SEC on
March 16, 2020, the company's
Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed with the SEC on
November 6, 2020, and in the
company's subsequent filings with the Securities and Exchange
Commission. Copies of these filings are available online at
www.sec.gov or ir.imux.com/sec-filings. Any forward-looking
statement made in this release speaks only as of the date of this
release. Immunic disclaims any intent or obligation to update these
forward-looking statements to reflect events or circumstances that
exist after the date on which they were made. Immunic expressly
disclaims all liability in respect to actions taken or not taken
based on any or all the contents of this press release.
Contact Information
Immunic, Inc.
Jessica Breu
Head of Investor Relations and Communications
+49 89 2080 477 09
jessica.breu@imux.com
US IR Contact
Rx Communications Group
Paula Schwartz
+1 917 322 2216
immunic@rxir.com
US Media Contact
KOGS Communication
Edna Kaplan
+1 781 639 1910
kaplan@kogspr.com
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