- First patient dosed with VX-880 demonstrated
restoration of insulin production and achieved C-peptide of 560
pmol/L in response to Mixed Meal Tolerance Test (MMTT) at Day 90
Visit -
- 91% decrease in daily insulin requirement and
simultaneous robust improvements in glucose control as measured by
HbA1c -
- Treatment was generally well tolerated -
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced positive Day 90 data for the first patient from the Phase
1/2 clinical trial of VX-880, an investigational stem cell-derived,
fully differentiated pancreatic islet cell replacement therapy for
people with type 1 diabetes (T1D). This is the first demonstration
of a patient with T1D achieving robust restoration of islet cell
function from such a cell therapy.
The patient was treated with a single infusion of VX-880 at half
the target dose in conjunction with immunosuppressive therapy. The
patient achieved successful engraftment and demonstrated rapid and
robust improvements in multiple measures, including increases in
fasting and stimulated C-peptide, improvements in glycemic control,
including HbA1c, and decreases in exogenous insulin requirement.
VX-880 was generally well tolerated.
“These results from the first patient treated with VX-880 are
unprecedented. What makes these results truly remarkable is that
they were achieved with treatment at half the target dose,” said
Bastiano Sanna, Ph.D., Executive Vice President and Chief of Cell
and Genetic Therapies at Vertex. “While still early, these results
support the continued progression of our VX-880 clinical studies,
as well as future studies using our encapsulated islet cells, which
hold the potential to be used without the need for
immunosuppression.”
“As a surgeon who has worked in the field of islet cell
transplantation for decades, this approach, which obviates the need
for an organ donor, could be a game changer,” said James Markmann,
M.D., Ph.D., Professor of Surgery and Chief of the Division of
Transplant Surgery at Massachusetts General Hospital. “We are
excited to progress this unique and potentially transformative
medicine through clinical trials and to patients.”
“More than a decade ago our lab had a vision for developing an
islet cell replacement therapy to provide a functional cure to
people suffering from T1D,” said Doug Melton, Ph.D., Xander
University Professor at Harvard and an Investigator of the Howard
Hughes Medical Institute. “These promising results bring great hope
that stem cell-derived, fully differentiated islet cells could
deliver a life-changing therapy for people who suffer from the
relentless life-long burden of T1D.”
Efficacy Results
The patient was diagnosed with T1D approximately 40 years ago
and has been dependent on exogenous insulin. In the one year prior
to treatment, the patient experienced 5 severe, potentially
life-threatening hypoglycemic episodes. Prior to treatment with
VX-880, the patient’s insulin dose was 34 units per day and fasting
and stimulated C-peptide levels were undetectable, indicating that
the patient was not making their own insulin. Per the study
protocol, the patient received half the target dose of VX-880
through a hepatic portal vein infusion in combination with a
standard regimen of immunosuppressive agents.
Fasting C-peptide, HbA1c and 7-day average daily insulin dose
were measured at various intervals after VX-880 treatment through
Day 90. Fasting C-peptide was detected early after treatment with
VX-880 and increased rapidly to Day 90. In parallel, HbA1c and
daily insulin dose decreased over time.
Islet cell function was evaluated at baseline and at Day 90
using a Mixed Meal Tolerance Test (MMTT) with quantification of
C-peptide levels, a direct marker for insulin production. At
baseline prior to VX-880 treatment, fasting and stimulated
C-peptide levels were undetectable, indicating no endogenous
insulin production. At Day 90 after VX-880 treatment, fasting
C-peptide was 280 pmol/L, reflecting restored basal insulin
production and increased after MMTT stimulation to a peak of 560
pmol/L, indicating that VX-880 restored glucose-responsive insulin
production. Also at Day 90, HbA1c improved from 8.6% at baseline to
7.2%, and daily insulin dose decreased from 34 units per day prior
to treatment with VX-880 to an average dose of 2.9 units per day
over a 7-day period at the Day 90 visit, reflecting a 91% decrease
in daily exogenous insulin use.
Baseline and Day 90 Measures
of Islet Cell Function for Patient 1
Baseline before
VX-880 infusion
Day 90 after
VX-880 infusion
Fasting C-peptide (pmol/L)
Undetectable*
280
Peak Stimulated C-peptide with
MMTT (pmol/L)
Undetectable*
560
HbA1c (%)
8.6
7.2
Daily insulin dose
(units/day)**
34
2.9
*The lower limit of quantitation of the C-peptide assay is 13
pmol/L. **Daily insulin dose for baseline was measured on Day -3
prior to VX-880 infusion. For Day 90 post-infusion, average daily
insulin dose was calculated over a 7-day period.
Safety Results
In this first patient, the safety of VX-880 was generally
consistent with the immunosuppressive regimen used in this study.
There were no serious adverse events (SAE) considered related to
VX-880, and the majority of the adverse events were considered mild
to moderate. The most common adverse events were severe
hypoglycemic events, which were non-serious, not related to VX-880,
and occurred in the perioperative period. Through Day 90, the
patient had one SAE; this was a rash that was mild in severity, not
related to VX-880, and resolved.
Next Steps
Based upon these data, Vertex plans to continue to progress the
Phase 1/2 program for VX-880. There are multiple active sites in
the U.S., and the Clinical Trial Application has been approved in
Canada. Vertex is also progressing IND-enabling studies for its
encapsulated islet cell program, which would potentially eliminate
the requirement for immunosuppression, and plans to file an IND for
this program in 2022.
About VX-880
VX-880 is an investigational allogeneic stem cell-derived, fully
differentiated, insulin-producing islet cell therapy manufactured
using proprietary technology. VX-880 is being evaluated for
patients who have T1D with impaired hypoglycemic awareness and
severe hypoglycemia. VX-880 has the potential to restore the body’s
ability to regulate glucose levels by restoring pancreatic islet
cell function, including glucose responsive insulin production.
VX-880 is delivered by an infusion into the hepatic portal vein and
requires chronic immunosuppressive therapy to protect the islet
cells from immune rejection.
About the Phase 1/2 Clinical Trial
The clinical trial is a Phase 1/2, multi-center, single-arm,
open-label study in patients who have T1D with impaired
hypoglycemic awareness and severe hypoglycemia. This study is
designed as a sequential, multi-part clinical trial to evaluate the
safety and efficacy of VX-880. The first two patients will be
treated with half the target dose, followed by dose escalation to
the target dose in the subsequent patients. Approximately 17
patients will be enrolled in the clinical trial. Enrollment is
ongoing in this study.
About Type 1 Diabetes
T1D results from the autoimmune destruction of insulin-producing
islet cells in the pancreas, leading to loss of insulin production
and impairment of blood glucose control. The absence of insulin
leads to abnormalities in how the body processes nutrients, leading
to high blood glucose levels. High blood glucose can lead to
diabetic ketoacidosis and over time, to complications such as
kidney disease/failure, eye disease (including vision loss), heart
disease, stroke, nerve damage and even death.
Due to the limitations and complexities of insulin delivery
systems, it can be difficult to achieve and maintain balance in
glucose control in patients with T1D. Hypoglycemia often results
because of the difficulty in balancing the different factors that
impact glucose levels, including insulin, diet and exercise.
Hypoglycemia remains a critical limiting factor in glycemic
management, and severe hypoglycemia can cause loss of
consciousness, coma, seizures, injury, and can be fatal. Over time,
patients with T1D can develop impaired awareness of hypoglycemia,
meaning they are no longer able to perceive the early signs of a
hypoglycemic event, which can be dangerous and result in life
threatening events.
Current standards of care do not address the underlying causes
of the disease, and there are limited treatment options beyond
insulin for the management of T1D.
About Vertex
Vertex is a global biotechnology company that invests in
scientific innovation to create transformative medicines for people
with serious diseases. The company has multiple approved medicines
that treat the underlying cause of cystic fibrosis (CF) — a rare,
life-threatening genetic disease — and has several ongoing clinical
and research programs in CF. Beyond CF, Vertex has a robust
pipeline of investigational small molecule medicines in other
serious diseases where it has deep insight into causal human
biology, including pain, alpha-1 antitrypsin deficiency and
APOL1-mediated kidney diseases. In addition, Vertex has a rapidly
expanding pipeline of cell and genetic therapies for diseases such
as sickle cell disease, beta thalassemia, Duchenne muscular
dystrophy and type 1 diabetes mellitus.
Founded in 1989 in Cambridge, Mass., Vertex's global
headquarters is now located in Boston's Innovation District and its
international headquarters is in London. Additionally, the company
has research and development sites and commercial offices in North
America, Europe, Australia and Latin America. Vertex is
consistently recognized as one of the industry's top places to
work, including 11 consecutive years on Science magazine's Top
Employers list and a best place to work for LGBTQ equality by the
Human Rights Campaign. For company updates and to learn more about
Vertex's history of innovation, visit www.vrtx.com or follow us on
Facebook, Twitter, LinkedIn, YouTube and Instagram.
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 Bastiano
Sanna, Ph.D., Dr. James Markmann, and Doug Melton, Ph.D. in this
press release, (ii) our plans, expectations for, and the potential
benefits of VX-880, (iii) our plans to continue to progress the
Phase 1/2 program for VX-880 and IND-enabling studies for the
encapsulated islet cell program, including anticipated regulatory
filings in 2022, and (iv) our plans for dosing and enrollment of
patients. 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, that data from one patient may not be indicative of final
clinical trial results, that data from the company's research and
development programs may not support registration or further
development of its compounds due to safety, efficacy, and other
risks listed under the heading “Risk Factors” in Vertex's most
recent annual report and subsequent quarterly reports 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, or the scientific data
presented. 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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