Vertex Announces Primary Endpoint Achieved in Phase 2 Study of VX-864 in Alpha-1 Antitrypsin Deficiency
June 10 2021 - 4:03PM
Business Wire
- Treatment with VX-864 led to a statistically
significant increase from baseline in plasma functional AAT levels
as compared to placebo and was generally well tolerated -
- Results provide proof-of-mechanism, although
magnitude of treatment effect observed unlikely to translate into
substantial clinical benefit; VX-864 will not advance into
late-stage development -
- Vertex to advance additional novel small
molecule(s) with potential for greater clinical efficacy into the
clinic in 2022 -
- Vertex will host an investor conference call
and webcast today, Thursday, June 10 at 4:30 p.m. EDT -
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced that in a Phase 2 proof-of-concept study, VX-864 achieved
rapid, consistent and statistically significant increases in mean
functional alpha-1 antitrypsin (fAAT) levels of 2.2 to 2.3
micromolar from baseline in people with alpha-1 antitrypsin
deficiency (AATD) with the PiZZ genotype, across three dose groups
of VX-864 compared to placebo. VX-864 was generally well tolerated
in the Phase 2 study. These data provide clear evidence that an
oral small molecule corrector designed to promote the proper
folding of the mutant Z-AAT protein can increase plasma levels of
fAAT in patients with AATD. Although results provide
proof-of-mechanism, the magnitude of treatment effect observed in
this study is unlikely to translate into substantial clinical
benefit. As such, Vertex will not advance VX-864 into late-stage
development and instead will advance additional novel small
molecule correctors with the potential for increased clinical
efficacy into the clinic.
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Figure 1: Statistically significant
increase in mean functional and antigenic AAT observed at day 28
compared to placebo (Graphic: Business Wire)
“This is the first time that dosing of a small molecule
corrector of the Z-AAT protein resulted in significant elevations
in both functional and antigenic levels of AAT in people with AATD.
We are encouraged by the clear separation of AAT levels in the
VX-864 treated groups versus placebo and the favorable safety
profile,” said Carmen Bozic, M.D., Executive Vice President, Global
Medicines Development and Medical Affairs, and Chief Medical
Officer at Vertex. “Based on these findings, we remain committed to
developing transformative treatments for AATD and are working with
urgency to translate the learnings from this study to optimize the
next set of small molecule correctors so that we can fully realize
the potential that this class of molecules may hold for people
living with this disease.”
Efficacy Results
The study met its primary endpoint, with all VX-864 dose groups
demonstrating highly statistically significant increases in plasma
fAAT levels from baseline compared to placebo at day 28 of
treatment. Treatment with VX-864 resulted in a mean increase of 2.2
to 2.3 micromolar in fAAT levels across the three dose groups
studied compared to placebo. All dose groups showed a rapid
increase in fAAT by day 7 which was sustained over 28 days of
treatment. Similar statistically significant increases in antigenic
AAT levels were observed compared to placebo, with a mean increase
of 2.7 to 3.5 micromolar across the three dose groups studied.
Plasma fAAT levels returned to baseline, in the 28-day safety
follow-up period following VX-864 discontinuation, consistent with
the half-life of native AAT protein and further confirming the
biological activity of VX-864.
Safety Results
In this study, VX-864 was generally well tolerated. All but one
patient completed treatment. There were no discontinuations due to
adverse events (AEs) and there were no serious adverse events
(SAEs) considered related to study drug. The majority of AEs were
mild or moderate in severity and not treatment limiting. The most
common AEs in VX-864 treated patients were diarrhea and nausea.
Liver function test (LFT) results were similar between the placebo
and VX-864 treated groups, and there was no evidence of any impact
on LFT results with VX-864.
Next Steps
The results of the VX-864 study demonstrated proof-of-mechanism
with a rapid, consistent and clear effect on functional and
antigenic AAT levels and a safety profile consistent with no
mechanism-related toxicity. The data collected are anticipated to
enable optimization of Vertex’s small molecule corrector approach
in AATD and the rapid progression of a portfolio of new molecules
with the potential for greater clinical efficacy into the clinic in
2022. In addition, the learnings from the VX-864 study are expected
to enable efficiencies in clinical trial design, enrollment and
execution for future assets.
About the Phase 2 Study in People with AATD
The Phase 2 study was a randomized, double-blind,
placebo-controlled study of the efficacy and safety of VX-864 in
people with the PiZZ genotype. People were randomized to one of
three dose groups of VX-864 or placebo for 28 days. In addition,
there was a 28-day follow-up period after the last dose of
treatment. The primary outcome measures were the mean change from
baseline in plasma fAAT levels at day 28 compared to placebo as
well as safety and tolerability of VX-864.
About Alpha-1 Antitrypsin Deficiency
AATD is a rare, genetic disease characterized by a protein
folding defect which can lead to liver and lung disease. AATD is
caused by changes in the SERPINA1 gene that encodes the AAT
protein. In the most common form of AATD, which occurs in people
with a PiZZ genotype, these changes to SERPINA1 cause the body to
produce misfolded AAT protein that gets trapped inside the liver,
where most AAT is made. This leads to low levels of AAT protein in
the blood. Low blood levels of AAT can allow inflammation to
proceed unchecked and damage the lungs. The accumulation of
defective AAT in the liver can also lead to liver disease. There is
currently no cure for AATD. There are also no treatments that
target the underlying protein folding defect that is the cause of
the disease.
Investor Webcast
The conference call will be webcast live, and a link to the
webcast can be accessed on the Vertex website at www.vrtx.com in
the “Investors” section. To access the call via phone, please dial
(866) 501-1537 (U.S.) or +1 (720) 545-0001 (International). To
ensure a timely connection, it is recommended that users register
at least 15 minutes prior to the scheduled webcast. An archived
webcast will be available on the companies’ website for
approximately 30 days.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as
defined in the Private Securities Litigation Reform Act of 1995, as
amended, including, without limitation, (i) statements by Dr.
Carmen Bozic in this press release, (ii) statements regarding the
company’s plans to advance additional novel small molecule(s) for
AATD into the clinic in 2022 and (iii) the statements set forth
under the caption “Next Steps” in this press release. While Vertex
believes the forward-looking statements contained in this press
release are accurate, these forward-looking statements represent
the company's beliefs only as of the date of this press release and
there are a number of risks and uncertainties that could cause
actual events or results to differ materially from those expressed
or implied by such forward-looking statements. Those risks and
uncertainties include, among other things, risks related to the
company’s AATD research programs, that data from the company's
research and development programs may not support registration or
further development of its compounds due to safety, efficacy, or
other reasons, and other risks listed under the heading “Risk
Factors” in Vertex's most recent annual report filed with the
Securities and Exchange Commission at www.sec.gov and available
through the company's website at www.vrtx.com. You should not place
undue reliance on these statements. Vertex disclaims any obligation
to update the information contained in this press release as new
information becomes available.
(VRTX-GEN)
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Vertex Pharmaceuticals Incorporated Investors:
Michael Partridge, +1 617-341-6108 or Brenda Eustace, +1
617-341-6187 or Manisha Pai, +1 617-429-6891 Media:
mediainfo@vrtx.com or U.S.: +1 617-341-6992 or Heather Nichols: +1
617-839-3607 or International: +44 20 3204 5275
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