InflaRx (Nasdaq: IFRX), a clinical-stage biopharmaceutical company
developing anti-inflammatory therapeutics by targeting the
complement system, today reported additional in-depth analysis of
the completed double blind, placebo controlled part of the ongoing
international SHINE Phase IIb study to supplement InflaRx’s top
line disclosure of results reported on June 5, 2019. The purpose of
this study is to investigate the safety and efficacy of IFX-1, a
first-in-class anti-human complement factor C5a monoclonal
antibody, in patients suffering from moderate to severe
Hidradenitis Suppurativa (HS), a painful and debilitating chronic
inflammatory skin disease with limited treatment options.
Prof. Niels C. Riedemann, CEO and Founder of
InflaRx, commented: “While we were very disappointed about missing
our primary endpoint in the SHINE study, our in depth post-hoc data
analysis suggests a robust anti-inflammatory activity in the high
dose IFX-1 treatment group across numerous efficacy measures which
were not reflected by the HiSCR. The company has made significant
efforts to research the available data set and has engaged with US
and European experts to assist in the analysis and interpretation
of these findings. Based on this, our team continues to work on the
development of IFX-1 in HS. We look forward to discussions with the
regulatory authorities upon completion of the open label extension
portion of the ongoing SHINE study,” he added.
The randomized, double-blind,
placebo-controlled, multicenter study, which enrolled a total of
179 patients in four active dose arms and a placebo arm at over 40
sites in North America and Europe, recently reported a failure to
achieve its primary endpoint, a dose dependent drug effect on
Hidradenitis Suppurativa Clinical Response Score (HiSCR). In order
to be a responder in this binary score, the total body count of
abscesses and inflammatory nodules (AN count) must be reduced by at
least 50% while the abscesses and draining fistula count may not
accede baseline counts. The score thus does not account for any
reduction in draining fistulas. The placebo arm demonstrated an
unusually high HiSCR response rate at week 16 of 47.2%, when
compared to earlier reported larger studies (Pioneer 1: 26% /
Pioneer 2: 27.6%, both at week 12). An in-depth patient by patient
data analysis revealed a very high variability of the HiSCR
responses in all trial groups, which was strongly affected by a
large individual fluctuation of the AN count.
The inclusion and exclusion criteria of the
SHINE study were nearly identical to the ones used in an earlier
published trial, the PIONEER II study, and the baseline
characteristics of the placebo group in the SHINE study were
comparable to those of the PIONEER II study with a good
distribution across all dose groups. This accounts especially for
the median AN count, median draining fistula count, gender
distribution, Hurley Stage II and III distribution and others.
Despite various additional efforts including post-hoc sensitivity
analysis on parameters like differences in HiSCR responder rates in
patients with low or high AN count at baseline, in Hurley II versus
III patients, in severe versus moderately diseased patients, as
well as clinical trial-site analysis, and several others, the
profound difference in the HiSCR response rates between these two
trials could not be explained by the results of these analyses.
Importantly, no underlying trial conduct problem to account for the
high placebo HiSCR rate could be detected.
InflaRx conducted an in-depth efficacy analysis
(secondary endpoints as well as additional post-hoc analysis) upon
receipt of the full data set of the first 16 weeks of the SHINE
study and, consecutively, consulted with key opinion leaders
(“KOL”) and members of its Scientific Steering Committee in the
United States, Canada and Europe. This analysis revealed multiple
efficacy signals for the high dose group when compared to the
placebo group:
At week 16, there was a statistically
significant reduction of draining fistulas (“DF”) relative to
baseline in the high dose IFX-1 group when compared to placebo
(Figure 1 – relating to all patients with at least 1DF at
baseline).
Figure
1: https://www.globenewswire.com/NewsRoom/AttachmentNg/102b6d10-3185-4a09-aba1-b12e95ba9924
This reduction in DF was visible as early as 2
weeks after induction of high dose IFX-1 therapy and consistent
over time with the strongest observed reductions seen at weeks 6, 8
and 16 (Figure 2). A temporary weakening of the strong reduction
was observed between weeks 10 to 14 which could not be explained by
pharmacokinetic or pharmacodynamic parameters. The strong relative
reduction of draining fistulas observed in the SHINE trial was
consistent with earlier findings in the open label Phase IIa study
(manuscript under revision for publication).
Figure
2: https://www.globenewswire.com/NewsRoom/AttachmentNg/9fcaafd4-571c-4338-87f2-c6d0d84a9d3b
As indicated in the initial press release from
June 5, 2019, IFX-1 therapy reduced the AN count at week 16
relative to baseline with a trend to a dose dependent effect.
Further analysis showed that high dose IFX-1 therapy reduced
abscesses and inflammatory nodule counts over time (Figure 3):
Figure
3: https://www.globenewswire.com/NewsRoom/AttachmentNg/2b70d9b6-e0a0-4e2f-b690-95c97cff501f
As a result of discussions with both the
Scientific Steering Committee and leading KOLs, InflaRx conducted
an additional post-hoc analysis utilizing the International
Hidradenitis Suppurativa Severity Score System (“IHS-4”), which is
scoring the patient according to all inflammatory lesions in
contrast to the HiSCR. In this compounded score, each inflammatory
nodule is counted with 1 point, each abscess with 2 points and each
draining fistula with 4 points. Patients scoring with 0-4 are
considered mild, with 5-10 moderate and with a score of 11 or
higher as severe. Applying the IHS-4 score, there was a
statistically significant relative change to baseline at the end of
the treatment period on week 16 (Figure 4) when comparing the high
dose IFX-1 treated group to placebo group. A trend to a dose
response across IFX-1 treated groups when compared to placebo could
be detected.
Figure
4: https://www.globenewswire.com/NewsRoom/AttachmentNg/d322d571-3a9a-485c-a854-45bca183af34
The relative change over time of the IHS-4 score
showed similar patterns in the placebo and high dose group when
compared to the relative change in DF with the strongest reductions
at week 6, 8 and 16 together with a temporary weakening of the
signal during week 10 to 14. Efficacy signals were also detected in
the high dose group for the Hidradenitis Suppurativa Physician
Global Assessment Score (“HS-PGA”), which scores patients’ severity
in six categories: clear, minimal, mild, moderate, severe and very
severe according to the amount and quality of inflammatory lesions.
IFX-1 treatment resulted in a more pronounced shift of severe and
very severe patients into groups of lower severity when compared to
the placebo group. This difference was most prominent on week 8 and
week 16. Patients shifting to the category clear disease were only
detected in IFX-1 treated groups but not in the placebo group at
week 16.
Pharmacokinetic and pharmacodynamic (“PK/PD”)
analysis demonstrated a dose dependent suppression of C5a and IFX-1
levels and suggested that the high dose group (1200mg q2w) offered
a superior control over C5a levels when compared to the other
dosing groups. IFX-1 treatment in all dose groups resulted in
sustained CH50 levels, as sign of an intact activation of the
membrane attack complex confirming earlier findings. The company is
running additional population PK analysis and statistical models to
estimate tissue PK, using all available data, to guide possible
future dosing and to estimate tissue penetration of IFX-1 in
HS.
The detection rate of confirmed anti-drug
antibodies (“ADA”) in the first 16 weeks of the SHINE trial was
overall low (<10% including pre-dose findings) for patients in
both the placebo group and the combined IFX-1 treated groups.
The company is continuing the open label
extension part of the SHINE trial with the last patient dosing
being expected for end of August 2019. Additional data will be
analyzed as it becomes available.
Conference call details:
Date: Friday, 19 July 2019 Time: 8 am
EDT, 2 pm CEST From the US: 877-407-0789 From
outside the US: +1 201-689-8562 Conference ID: 13692883To join the
audio-only webcast, register here:
http://public.viavid.com/index.php?id=135498Please dial in 10
minutes before the call to register.
About IFX-1:IFX-1 is a
first-in-class monoclonal anti-human complement factor C5a
antibody, which highly and effectively blocks the biological
activity of C5a and demonstrates high selectivity towards its
target in human blood. Thus, IFX-1 leaves the formation of the
membrane attack complex (C5b-9) intact as an important defense
mechanism, which is not the case for molecules blocking the
cleavage of C5. IFX-1 has been demonstrated to control the
inflammatory response driven tissue and organ damage by
specifically blocking C5a as a key “amplifier” of this response in
pre-clinical studies. IFX-1 is believed to be the first monoclonal
anti-C5a antibody introduced into clinical development and has, to
date, successfully completed three clinical Phase II studies. More
than 150 people have been treated with IFX-1 in these completed
clinical trials, and the antibody has been shown to be well
tolerated. IFX-1 is currently being developed for various
inflammatory indications, including Hidradenitis Suppurativa,
ANCA-associated vasculitis and Pyoderma Gangraenosum.
About InflaRx N.V.: InflaRx
(Nasdaq: IFRX) is a clinical-stage biopharmaceutical company
focused on applying its proprietary anti-C5a technology to discover
and develop first-in-class, potent and specific inhibitors of C5a.
Complement C5a is a powerful inflammatory mediator involved in the
progression of a wide variety of autoimmune and other inflammatory
diseases. InflaRx was founded in 2007 and the group has offices and
subsidiaries in Jena and Munich, Germany, as well as Ann Arbor, MI
and New York, NY, USA. For further information please visit
www.inflarx.com.
Contacts:Investor
RelationsInflaRx N.V.Jordan
SilversteinHead of Corporate Development and
StrategyJordan.silverstein[at]inflarx.de+1 917-837-1709
Media RelationsMC
Services AGKatja Arnold, Laurie Doyle, Andreas
Jungferinflarx[at]mc-services.eu+49 89-210 2280
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