PHARNEXT SCA 
Pharnext Press Release
Pharnext Announces Encouraging Data from Open-Label Phase 3 Extension Study of PXT3003 in Charcot-Marie-Tooth Disease Type 1A (CMT1A)
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 (FR0011191287 - ALPHA), abiopharmaceutical 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:
"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 providefurtherargumentthat 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 extensionstudy into an open-label study) andall placebo patients were only assigned to the low dose (D1) arm. Out of the 323 patients enrolled in PLEO-CMT, 187 patients entered the extensionstudy, 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):
PLEO-CMT-FU Results A preliminary efficacy analysis of ONLS, a disability scale which is the primary endpoint of PLEO-CMT, showed animprovement in all groups in PLEO-CMT-FU when compared to placebo patients (pooled P-D1 + P-D2) during the PLEO-CMTstudy(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 switchingto 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-FUon 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 observedover approximately 25 months of trial despite a mean of 5months of interruption (see graph in annex).Highlights include:
This extension study was open-label and therefore should be cautiously interpreted, but these preliminary results would further support the potential long-termbenefit of PXT3003 for CMT1A patients. Pharnextexpects 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. 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(TM). Pharnext identifies and develops synergic combinations of drugs called PLEODRUG(TM). 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. 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.
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[1]Post-hoc analysis [2]Open-label clinical trialmeans 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 | ||||||||||||||||||||||||
947463 06-Jan-2020 CET/CEST
