Full Press Release Details
Akari Therapeutics demonstrates positive
response with Coversin in ongoing phase 2 PNH trial and in additional clinical targets
-Interim Phase 2 PNH data demonstrate positive response with
-Phase 3 PNH program expected to commence in 4Q2017
-Data from preclinical aHUS model demonstrates positive results
-New preclinical data demonstrates positive response of Coversin's
combined C5 and LTB4 therapy in skin and eye models
-Phase 2 programs in Mucous Membrane Pemphigoid (eye) and
Bullous Pemphigoid (Skin) expected to commence in 1Q2018
-Company to webcast today's Research and Development Day
at 8:00 am Eastern (details below)-
NEW YORK and LONDON, April 24, 2017 (GLOBE
NEWSWIRE) -- Akari Therapeutics (NASDAQ: AKTX), an emerging growth, clinical-stage biopharmaceutical company, announced that it
will present data from an interim analysis of its ongoing Phase 2 trial of Coversin in paroxysmal nocturnal hemoglobinuria (PNH),
as well as preclinical data for additional indications and other opportunities, at today's Research and Development Day.
Positive Interim Phase 2 data in PNH
In this 90 day, open label Phase 2 trial
conducted at five centers in the EU, five patients with PNH who had not received prior anti-complement therapy were enrolled and
treated with Coversin self-administered subcutaneous injections twice a day for approximately the first month and then switched
to once daily injections. The primary endpoint in this trial is reduction in serum LDH to 1.8 X ULN or 500 I U/L whichever
is the lower from day 1 (pre-dose) to day 28. Secondary endpoints are LDH at days 60 and 90, hemoglobin, CH50, quality of life,
and transfusion independence. The objectives of our Phase 2 study are to validate the safety and efficacy of Coversin, confirm
convenience of our dosing regimen, and study dose ranging to identify the correct treatment dose in advance of Phase 3.
The 4 patients who remain on Coversin are
characterized, to date, by:
In this dose ranging Phase 2 study, the
protocol allowed for patients to be updosed from the 30mg starting dose. Of the 4 patients continuing on Coversin: the first patient's
LDH went from 2.4X ULN at baseline to 2.1X ULN on the starting dose, was updosed to 45 mg and achieved a reduction to 1.3X ULN
on day 28 and remains on 45mg once daily injections; the second patient with an LDH of 7.5X ULN at baseline, achieved a reduction
to 1.4X ULN on day 28 with the starting dose, and remains on 30mg once daily injections; the third patient's LDH went from
3.3X ULN at baseline to 2.4X ULN on the starting dose, was updosed to 45 mg and achieved a reduction to 1.5X ULN on day 60 and
remains on 45mg once daily injections; and the fourth patient who just reached the 6 week mark for this interim analysis achieved
an LDH reduction from 5.6 X ULN at baseline to 1.8X ULN on day 40 on the starting dose, and was updosed to 45mg on day 48 and continues
on once daily injections. All 4 patients achieved on day 1 and throughout the trial a CH50 below the lower limit of quantification
A fifth patient with an LDH of 3.7 X ULN
at baseline achieved the primary endpoint at day 14, but was withdrawn from the trial at day 43 due to a suspected co-morbidity
unrelated to treatment, which would have excluded the patient from the trial protocol. While on Coversin, the patient met the primary
endpoint (day 14), and achieved and maintained a CH50 <LLQ (day 1) but clinical response fluctuated and did not stabilize. After
withdrawal, the patient switched to eculizumab. On eculizumab, LDH decreased to below 1.5X ULN and the patient experienced other
clinical complications.
As reported previously, an eculizumab-resistant PNH patient
had been under treatment with subcutaneous Coversin for over 14 months under an approved clinical protocol. The patient continues
to self-administer Coversin and continues to demonstrate complete complement inhibition without any change in dose. The patient's
most recent reported LDH was below 1.3 X ULN. Further, there have been no signs of neutralizing antibodies.
All patients are comfortable with self-dosing
and by the end of May, we plan to have the four continuing patients from this Phase 2 and the one patient from the eculizumab resistant
protocol on long term treatment in our long term open label safety trial. Akari is planning to initiate its Phase 3 program in
PNH in the fourth quarter of 2017 and anticipates initial Phase 3 data 1Q2019.
Recent studies with Coversin have demonstrated
positive results in a preclinical model of atypical hemolytic uremic syndrome (aHUS) conducted by Prof. Giuseppe Remuzzi and colleagues
Marina Noris and Miriam Galbusera at the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, and the Clinical
Research Center for Rare Diseases "Aldo e Cele Dacco" of the same institute, a European center for the study of aHUS.
In a well-established ex vivo model testing sera of patients with aHUS, Coversin demonstrated a statistically significant (p<0.001)
reduction in membrane attack complex (MAC) deposition on endothelial cells when activated by sera of patients with active aHUS,
at least as well as eculizumab. Akari expects to initiate its Phase 2 trial in aHUS in 2Q2017, and anticipates Phase 2 aHUS data
New data demonstrating Coversin C5 and
LTB4 dual activity in eye and skin models
Akari will present new data on its clinical
development plan for Coversin based on its dual C5/LTB4 inhibition, focusing on new clinical indications in the eye and skin.
Results in a rodent model of Experimental
Immune Conjunctivitis (EIC), undertaken at the world leading Moorfields Hospital Institute of Ophthalmology, showed that Coversin
demonstrated significant anti-inflammatory activity with both C5 and LTB4 inhibition believed to play a role. In this preclinical
model of severe eye surface inflammation, Coversin, applied topically, resulted in a statistically significant reduction (64%,
p<0.001) in late phase inflammation versus placebo.
In a pre-clinical mouse model of bullous
pemphigoid (a blistering disease of the skin), where both LTB4 and C5 are thought to be dysregulated, Coversin demonstrated a statistically
significant reduction (~60%, p=0.002) in affected area with Coversin compared to placebo and steroids
Based on these results, Akari, while continuing
to develop Coversin in PNH and aHUS, also intends to focus on new indications for Coversin in diseases where both C5 and LTB4 are
believed to be involved. Akari expects to commence in 1Q2018 randomized, double blind Phase 2 trials in patients with bullous pemphigoid
who are refractory to oral steroids as well in mucous membrane pemphigoid (eye) and anticipates Phase 2 data from these trials
Akari will present an update on its pipeline
of new molecules including:
Akari anticipates further preclinical
pipeline data in 3Q2017.
The R&D Day presentation, scheduled
to begin at 8:00am EDT today, April 24, 2017, will be webcast live and can be accessed by following the link on the homepage of
our website (www.akaritx.com) as well as through the "Link to Simulcast for April 24th R&D Day" which appears on
the left side of the "Investor Relations" section of Akari's website.
About Akari Therapeutics Plc
Akari is a clinical-stage biopharmaceutical
company focused on the development and commercialization of life-transforming treatments for a range of rare and orphan autoimmune
and inflammatory diseases caused by dysregulation of complement C5 and Leukotriene B4 (LTB4), including paroxysmal nocturnal hemoglobinuria
("PNH"), atypical Hemolytic Uremic Syndrome ("aHUS"), and Guillain Barr syndrome ("GBS").
Akari's lead product candidate, Coversin complement inhibitor, a second-generation complement inhibitor, acts on complement
component-C5, preventing the release of C5a and the formation of C5b-9 (also known as the membrane attack complex or MAC),
and independently also inhibits LTB4 activity. C5 inhibition is growing in importance in a range of rare autoimmune diseases related
to dysregulation of the complement component of the immune system, including PNH, aHUS, and GBS. Exploiting the power of nature,
Akari is also developing other tick derived proteins and expects to bring additional compounds to clinical trials over the next
several years. The pipeline is focused on developing bioengineered versions of native tick salivary proteins that act as anti-inflammatory
compounds allowing the tick to remain on its host. These compounds include PGP sparing LTB4 inhibitors, classical and alternative
complement inhibitors, anti-histamines, and serotonin inhibitors as examples. Akari is also developing engineered forms that allow
for potential oral absorption, as, for example, a potential orally absorbed C5 inhibitor, and tissue specific proteins, as, for
example, Coversin that acts specifically at the neuromuscular junction for diseases like myasthenia gravis
Cautionary Note Regarding Forward-Looking Statements
Certain statements in this press release
constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995.
These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects,
which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans,
intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable,