Wave Life Sciences Announces Initiation of Dosing in Phase 1b/2a SELECT-HD Clinical Trial of WVE-003 in Huntington’s Disease
September 09 2021 - 8:30AM
Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic
medicines company committed to delivering life-changing treatments
for people battling devastating diseases, today announced the
initiation of dosing in the company’s Phase 1b/2a SELECT-HD
clinical trial evaluating investigational WVE-003 as a treatment
for Huntington’s disease (HD). WVE-003 is a stereopure antisense
oligonucleotide designed to target SNP3, a single nucleotide
polymorphism on the mutant huntingtin (mHTT) allele, thereby
selectively lowering mHTT protein and sparing healthy, wild-type
huntingtin (wtHTT) protein.
“WVE-003 reflects the significant evolution of our chemistry and
the many learnings gained from our first-generation clinical
programs,” said Michael Panzara, MD, MPH, Chief Medical Officer and
Head of Therapeutics Discovery and Development at Wave Life
Sciences. “Our enthusiasm for this program is bolstered by a
compelling set of preclinical data that demonstrated selectivity,
potency, and durability of WVE-003 with effects in relevant brain
regions. Further, emerging data continue to indicate that a
fundamental requirement for clinical success in HD treatment will
be the need to preserve wild-type HTT protein, supporting our
allele-selective approach to mutant HTT protein reduction.”
Wave’s approach to HD and the WVE-003 program is guided by the
recognition that, in addition to a gain of function of the mHTT
protein, people with this disease have lost one copy of the wtHTT
allele, leaving them with a smaller protective reservoir of healthy
protein than unaffected individuals. A growing body of scientific
evidence suggests that preserving as much of this essential wtHTT
protein as possible, when in the setting of stress from the toxic
mHTT protein, may be important for favorable clinical outcomes.
WVE-003 incorporates the company’s novel PN backbone chemistry
modifications (PN chemistry), which have been shown in preclinical
studies to enhance potency, exposure, and durability. In
preclinical studies, WVE-003 demonstrated dose-dependent and
selective reduction of mHTT mRNA in vitro and potent and durable
knockdown of mHTT mRNA in vivo, in both the cortex and striatum.
Data from several preclinical models evaluating pharmacokinetic to
pharmacodynamic relationships for WVE-003 have informed the
starting dose for the SELECT-HD trial.
The SELECT-HD trial is a global, multicenter, randomized,
double-blind, placebo-controlled Phase 1b/2a clinical trial to
assess the safety and tolerability of single- and
multiple-ascending intrathecal doses of WVE-003 in people with a
confirmed diagnosis of HD who are in the early stages of the
disease and carry SNP3 in association with their
cytosine-adenine-guanine (CAG) expansion. It is estimated that
approximately 40 percent of adults with HD carry SNP3 in
association with the HD mutation. Additional objectives include
assessing the plasma pharmacokinetic profile and exposure in the
cerebrospinal fluid, as well as exploratory pharmacodynamic (mHTT,
wtHTT and neurofilament light chain) and clinical endpoints. The
SELECT-HD trial is expected to enroll approximately 36 patients. It
is designed to be adaptive, with dose escalation and dosing
frequency being guided by an independent committee.
The SELECT-HD trial design and WVE-003 preclinical data will be
highlighted in plenary and poster sessions at the EHDN 2021 Remote
Meeting, taking place September 9-11, 2021. Presentation details
are as follows:
- Friday, September 10 at 8:05 a.m. EDT (2:05 p.m.
CEST)SELECT-HD, an adaptive first-in-human clinical trial
to evaluate WVE-003, an investigational allele-selective
mHTT-lowering oligonucleotide, in early manifest Huntington's
disease (Vissia Viglietta, MD, PhD, Vice President of Clinical
Development and Medical Affairs at Wave Life Sciences)Plenary
Session III: Clinical Trial Session
- Thursday, September 9 – Saturday, September
11Design of an Adaptive Randomized Controlled Phase 1b/2a
Trial of WVE-003 in Participants with Huntington’s Disease (Danlin
Xu, PhD, Medical Director at Wave Life Sciences)Poster Available On
Demand
About Huntington’s Disease Huntington’s disease
(HD) is a debilitating and ultimately fatal autosomal dominant
neurological disorder, characterized by cognitive decline,
psychiatric illness, and chorea. HD causes nerve cells in the brain
to deteriorate over time, affecting thinking ability, emotions, and
movement. HD is caused by an expanded cytosine-adenine-guanine
(CAG) triplet repeat in the huntingtin (HTT) gene that results in
production of mutant HTT (mHTT) protein. Accumulation of mHTT
causes progressive loss of neurons in the brain. Wild-type, or
healthy, HTT (wtHTT) protein is critical for neuronal function and
suppression may have detrimental long-term consequences.
Approximately 30,000 people in the United States have symptomatic
HD and more than 200,000 others are at risk for developing the
disease. There are currently no approved disease-modifying
therapies available.
About Wave Life SciencesWave Life Sciences
(Nasdaq: WVE) is a clinical-stage genetic medicines company
committed to delivering life-changing treatments for people
battling devastating diseases. Wave aspires to develop
best-in-class medicines across multiple therapeutic modalities
using PRISM, the company’s proprietary discovery and drug
development platform that enables the precise design, optimization
and production of stereopure oligonucleotides. Driven by a resolute
sense of urgency, the Wave team is targeting a broad range of
genetically defined diseases so that patients and families may
realize a brighter future. To find out more, please visit
www.wavelifesciences.com and follow Wave on Twitter
@WaveLifeSci.
Forward-Looking StatementsThis press release
contains forward-looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995, as amended,
including, without limitation, the anticipated therapeutic benefit
of WVE-003 as an investigational therapy for HD; our belief
regarding the learnings gained from our first-generation clinical
programs; the anticipated timing of data to enable decision-making
on next steps for WVE-003; the predicted pharmacology of WVE-003
and the associated trial protocol, design and endpoints; our
beliefs related to the cause of HD; our understanding of how mHTT
and wtHTT impact HD to guide our WVE-003 program; expected patient
enrollment in the SELECT-HD trial; the anticipated therapeutic
benefits of our potential therapies, including our compounds
containing PN chemistry, compared to others; and the potential
benefits of PRISM, including our novel PN backbone chemistry
modifications, and our stereopure oligonucleotides compared with
stereorandom oligonucleotides. The words “may,” “will,” “could,”
“would,” “should,” “expect,” “plan,” “anticipate,” “intend,”
“believe,” “estimate,” “predict,” “project,” “potential,”
“continue,” “target” and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements in this press release are based on
management's current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed
or implied by any forward-looking statements contained in this
press release and actual results may differ materially from those
indicated by these forward-looking statements as a result of these
risks, uncertainties and important factors, including, without
limitation, the risks and uncertainties described in the section
entitled “Risk Factors” in Wave’s most recent Annual Report on Form
10-K filed with the Securities and Exchange Commission (SEC), as
amended, and in other filings Wave makes with the SEC from time to
time. Wave undertakes no obligation to update the information
contained in this press release to reflect subsequently occurring
events or circumstances.
Investor Contact:Kate
Rausch617-949-4827krausch@wavelifesci.com
Media Contact:Alicia
Suter617-949-4817asuter@wavelifesci.com
Patient Community Contact:Wave Patient
Advocacypatientadvocacy@wavelifesci.com
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