Pharnext
Pharnext Announces Encouraging Data from Open-Label Phase 3 Extension Study of PXT3003
in Charcot-Marie-Tooth Disease Type 1A (CMT1A)
06-Jan-2020 / 19:00 CET/CEST
Dissemination of a French Regulatory News, transmitted by EQS Group.
The issuer is solely responsible for the content of this announcement.
Press Release
Pharnext Announces Encouraging Data from Open-Label Phase 3 Extension Study of PXT3003
in Charcot-Marie-Tooth Disease Type 1A (CMT1A)
· Results suggest sustained safety and efficacy of PXT3003 in CMT1A patients after
25 months of total trial time (Phase 3 trial + open-label extension study)
· CMT1A patients showed improvement or stabilization of disease as measured by the
Overall Neuropathy Limitations Scale during the open-label Phase 3 extension study
Conference call in English today at 10:30 p.m. CET (4:30 p.m. ET)
Conference call in French on Tuesday January 7 at 10:00 a.m. CET (4:00 a.m. ET)
PARIS, France, 07:00 p.m., January 6, 2020 (CET) - Pharnext SA [1] (FR0011191287 -
ALPHA), a biopharmaceutical company pioneering a new approach to developing innovative
drug combinations based on big genomics data and artificial intelligence, today
announced encouraging data from the open-label Phase 3 extension study of PXT3003 in
patients with Charcot-Marie-Tooth Disease Type 1A (CMT1A).
Data from 185 patients in the 9-month PLEO-CMT open-label extension study
(PLEO-CMT-FU) were consistent with prior positive safety and tolerability results in
the 15-month, double-blind Phase 3 study (PLEO-CMT). Highlights from a preliminary
efficacy analysis[1] of the open-label PLEO-CMT-FU study include:
· Patients improved on the Overall Neuropathy Limitation Scale (ONLS) across all
dose cohorts during the extension study as compared to the ONLS decline seen in the
placebo group.
· Patients treated with PXT3003 since the start of the Phase 3 program showed ONLS
improvement or remained stable at the end of the PLEO-CMT-FU extension study as
compared to the ONLS at the beginning of the PLEO-CMT study.
· Patients with a decline in ONLS during their treatment interruption improved upon
resuming treatment.
"These data further reinforce our confidence in the safety and efficacy signals from
the previous clinical studies," said Daniel Cohen, M.D., Ph.D., co-founder and Chief
Executive Officer of Pharnext. "We look forward to continuing our discussions with the
U.S. Food and Drug Administration (FDA) and expect to align on the design of an
additional pivotal Phase 3 trial in the first half of 2020, with the goal of
initiating the study as soon as possible."
"Patients with CMT1A have no pharmacological treatment options for their chronic,
progressive hereditary disease," said Prof. Dr. med. Maggie C. Walter, M.A., Associate
Professor of Neurology, Friedrich-Baur-Institute, Dept. of Neurology,
Ludwig-Maximilians-University of Munich, Germany. "Although these data were generated
from an open-label study, the data seem to support the efficacy signal observed in the
primary Phase 3 trial and suggest potential sustained efficacy over the course of two
years."
Prof. Florian P. Thomas, M.D., M.A., Ph.D., M.S., Founding Chair & Professor,
Department of Neurology, Hackensack Meridian School of Medicine, Hackensack, NJ, USA,
said: "These results provide further argument that PXT3003 could potentially stabilize
and even improve neurological function in patients with CMT1A. I am excited by these
results and the potential for PXT3003 to serve as a novel and safe therapeutic
approach for CMT1A patients."
PLEO-CMT-FU Study Design
PLEO-CMT-FU is a 9-month, open-label[2], extension study designed to assess the
long-term safety and tolerability of PXT3003 in patients who completed the PLEO-CMT
study, a 15-month, double-blind Phase 3 study that assessed the efficacy and safety of
PXT3003 in 323 CMT1A patients aged 16 to 65 years. In October 2018, Pharnext announced
that PXT3003 met the primary endpoint of ONLS in PLEO-CMT, with a statistically
significant difference between the high dose arm and the placebo group (p=0.008).
Patients in the low dose (D1) or high dose (D2) arm in PLEO-CMT who opted into the
PLEO-CMT-FU study continued at the same respective dose level (D1-D1 or D2-D2), while
patients in the placebo arm in PLEO-CMT who chose to participate were randomized 1:1
into the D1 or D2 cohorts (P-D1 or P-D2, respectively). An unexpected intercurrent D2
formulation event in September 2017 led to a discontinuation of the high dose (D2) arm
and an interruption in treatment for some subjects either during the Phase 3 PLEO-CMT
study, during the PLEO-CMT-FU study, or between the two studies. Following this event,
high dose (D2) patients in the extension study received twice the volume of the low
dose (D1) formulation in order to deliver the high dose (this unblinding converted the
extension study into an open-label study) and all placebo patients were only assigned
to the low dose (D1) arm.
Out of the 323 patients enrolled in PLEO-CMT, 187 patients entered the extension
study, PLEO-CMT-FU, of which 185[3] were analyzed, with 62 in the D1-D1 group, 69 in
the D2-D2 group, 46 in the P-D1 group and 8 in the P-D2 group.
Data was then grouped for three distinct time periods (see graph in annex):
1) PLEO-CMT: double-blind Phase 3 study (two doses of PXT3003 versus placebo)
2) Interruption
3) PLEO-CMT-FU: analysis only includes the longest uninterrupted treatment period
during the extension study
PLEO-CMT-FU Results
A preliminary efficacy analysis of ONLS, a disability scale which is the primary
endpoint of PLEO-CMT, showed an improvement in all groups in PLEO-CMT-FU when compared
to placebo patients (pooled P-D1 + P-D2) during the PLEO-CMT study (estimate/year[4]:
-0.30, 95% CI [-0.48; -0.12], p = 0.001). Patients on the placebo arm (pooled P-D1 +
P-D2) during the Phase 3 PLEO-CMT study, after switching to dose D1 or D2 during
PLEO-CMT-FU, demonstrated an ONLS improvement when compared to their ONLS decline in
the PLEO-CMT study (estimate/year4: -0.24, 95% CI [-0.47; -0.01], p= 0.038).
Results of both studies: PLEO-CMT and PLEO-CMT-FU including interruption period
Patients on D1 or D2 during both PLEO-CMT and PLEO-CMT-FU on average remained stable
or improved in ONLS at the end of the PLEO-CMT-FU study as compared to the beginning
of the PLEO-CMT study. This ONLS change was observed over approximately 25 months of
trial despite a mean of 5 months of interruption (see graph in annex). Highlights
include:
· Patients in D2-D2 (n=69), on average, had lower duration of treatment (9.5 months)
during PLEO-CMT due to the D2 arm discontinuation following the D2 formulation
intercurrent event. These patients in D2-D2 then seemed to remain stable on the ONLS
disability scale during an 8-month mean interruption. A trend to improvement was
observed upon resuming treatment during a mean of 8 months (see graph in annex). The
cumulative change over 25 months of total trial time showed a -0.26 point ONLS
improvement.
· Patients in D1-D1 (n=62) experienced a decline of +0.14 point ONLS (SE = 0.06)
during a 2-month mean interruption while improving -0.12 point ONLS (SE = 0.08) upon
resuming treatment.
This extension study was open-label and therefore should be cautiously interpreted,
but these preliminary results would further support the potential long-term benefit of
PXT3003 for CMT1A patients.
Pharnext expects to keep patients currently enrolled in the Phase 3 extension study on
treatment until PXT3003 is commercially available.
Pharnext plans to provide a more detailed analysis during the first half of 2020.
Regulatory Update
In August 2019, the FDA asked that Pharnext conduct an additional Phase 3 study to
evaluate PXT3003 in CMT1A due to the large amount of missing data caused by the
intercurrent event in the Phase 3 PLEO-CMT study. The Company expects to align with
the FDA on the protocol for this second Phase 3 study in the first half of 2020.
Pharnext also plans to use the additional Phase 3 study to support a Marketing
Authorization Application in Europe and thus align the European and U.S. regulatory
plans.
Conference Call
Pharnext will host a live conference call and webcast at 10:30 p.m. CET (4:30 p.m. ET)
today to discuss the data. The conference call may be accessed by dialing 0170807153
(France), 866-417-2001 (USA), or 409-217-8230 (International) and referring to
conference ID 9786868. A live webcast and accompanying slides will be available on the
Pharnext website at www.pharnext.com/en/investors/presentation [2]. An archived
webcast will be available on Pharnext's website approximately two hours after the
conference call.
Pharnext will also host a live conference call in French at 10:00 a.m. CET (4:00 a.m.
ET) on Tuesday January 7. The conference call may be accessed by dialing 0176772819
(France), 800-497-0398 (USA) and referring to conference ID 9069392.
About Pharnext
Pharnext is an advanced clinical-stage biopharmaceutical company developing novel
therapeutics for orphan and common neurodegenerative diseases that currently lack
curative and/or disease-modifying treatments. Pharnext has two lead products in
clinical development. PXT3003 completed an international Phase 3 trial with positive
topline results for the treatment of Charcot-Marie-Tooth disease type 1A and benefits
from orphan drug status in Europe and the United States. PXT864 has generated
encouraging Phase 2 results in Alzheimer's disease. Pharnext has developed a new drug
discovery paradigm based on big genomics data and artificial intelligence:
PLEOTHERAPY. Pharnext identifies and develops synergic combinations of drugs
called PLEODRUG. The Company was founded by renowned scientists and entrepreneurs
including Professor Daniel Cohen, a pioneer in modern genomics, and is supported by a
world-class scientific team. More information at www.pharnext.com [3].
Pharnext is listed on the Euronext Growth Stock Exchange in Paris (ISIN code:
FR0011191287).
Disclaimer:
This press release contains certain forward-looking statements concerning Pharnext and
its business. Such forward-looking statements are based on assumptions that Pharnext
considers to be reasonable. However, there can be no assurance that the estimates
contained in such forward-looking statements will be verified, which estimates are
subject to numerous risks including the risks set forth in Pharnext's document de base
filed with the AMF on June 2, 2016 under number I.016-0050 as well as in its annual
periodic management reports and press releases (copies of which are available on
www.pharnext.com) and to the development of economic conditions, financial markets and
the markets in which Pharnext operates. The forward-looking statements contained in
this press release are also subject to risks not yet known to Pharnext or not
currently considered material by Pharnext. The occurrence of all or part of such risks
could cause actual results, financial conditions, performance or achievements of
Pharnext to be materially different from such forward-looking statements. Pharnext
disclaims any intention or obligation to publicly update or revise any forward-looking
statements, whether as a result of new information, future events, or otherwise.
This press release and the information that it contains do not constitute an offer to
sell or subscribe for, or a solicitation of an offer to purchase or subscribe for,
Pharnext shares in any country.
Contacts:
Pharnext
Daniel Cohen
Chief Executive
Officer
contact@pharnext.com
+33 (0)1 41 09 22 30
Financial Communication Investor Relations Investor Relations (Europe)
(France) (U.S.)
MC Services AG
Actifin Stern Investor
Relations, Inc.
Anne Hennecke
Stéphane Ruiz
Jane Urheim
anne.hennecke@mc-services.eu
sruiz@actifin.fr
Jane.urheim@sternir.com
+49 211 529252 22
+33 (0)1 56 88 11 15
+1 212 362 1200
Media Relations (Europe)
Ulysse Communication
Bruno Arabian
barabian
[4]@ulysse-communication.com
+33 (0)1 81 70 96 30
=-------------------------------------------------------------------------------------
[1] Post-hoc analysis
[2] Open-label clinical trial means that study participants and investigators both
know which treatment the patient is receiving. Open-label trials can be used to
compare treatments or gather additional information about the long-term effects in the
intended patient population. Patients who completed the Phase 3 PLEO-CMT clinical
trial were eligible to continue in the PLEO-CMT-FU open-label study where all
participants are eligible to receive active treatment for an extended period of time.
[3] 187 patients were enrolled; however, 2 patients were excluded as outliers due to
extraordinary circumstances considered unrelated to treatment.
[4] A negative estimated change to the ONLS score means clinical improvement.
Regulatory filing PDF file
Document title: Press_release_PXT3003_extension_study_Jan6_2020
Document: http://n.eqs.com/c/fncls.ssp?u=TPHGFLRBDR [5]
947463 06-Jan-2020 CET/CEST
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(END) Dow Jones Newswires
January 06, 2020 13:00 ET (18:00 GMT)
