‒
Phase 3 Clinical Trial of NeoCart Did Not Meet Primary Endpoint of
a Statistically Significant Improvement in Pain and Function in a
Dual Threshold Responder Analysis One Year After Treatment as
Compared to Microfracture ‒
‒ NeoCart Demonstrated Statistically Significant and
Clinically Meaningful Improvements on Dual Threshold Responder
Analysis Six Months After Treatment and Nearly All Pain and
Function Measures Compared to Microfracture One and Two Years After
Treatment ‒ ‒ Data
Compared Favorably to Other Products on the Market or in
Development Per Guidance from the U. S. Food and Drug
Administration ‒ ‒
Company to Discuss Plans for Submission of Biologics License
Application with U.S. Food and Drug Administration ‒
‒ Company to Host Conference Call
and Webcast Today at 8:30 a.m. ET ‒
Histogenics Corporation (Histogenics) (Nasdaq: HSGX), a leader in
the development of restorative cell therapies that may offer
rapid-onset pain relief and restored function, today announced that
its Phase 3 clinical trial of NeoCart did not meet the primary
endpoint of a statistically significant improvement in pain and
function in a dual threshold responder analysis one year after
treatment as compared to microfracture. In the modified
Intent to Treat (mITT) population (which excludes those patients
who were randomized but not treated with NeoCart), 74.2% of the
NeoCart patients exhibited clinically meaningful improvements in
pain and function compared to 62.0% of microfracture patients at
one year (p=0.071). However, in this mITT population,
patients treated with NeoCart achieved a statistically significant
improvement in pain and function (p=0.018) six months after
treatment as compared to patients treated with microfracture.
Both NeoCart and microfracture were well tolerated and exhibited
strong safety profiles.
“Based on the totality of the data generated in
the Phase 3 clinical trial, we continue to believe in NeoCart’s
potential as a treatment for knee cartilage damage. When we
designed our Phase 3 clinical trial in 2009, we set a very high
clinical bar for NeoCart and narrowly missed hitting the trial’s
primary endpoint with statistical significance by only two
microfracture responders out of the 249 patients that participated
in the trial. While the NeoCart treatment group exhibited a
response as early as three months after treatment that continued
through two years, the microfracture response rate was better than
expected, which impacted the statistics. We are encouraged by
the results and believe we have a meaningfully differentiated
product that, if approved, can compete effectively and provide
physicians and patients with a beneficial treatment option that may
grow the market,” said Adam Gridley, President and Chief Executive
Officer of Histogenics. “We continue to analyze the data and
are in the process of scheduling a meeting with the FDA to discuss
the results and prepare for a potential submission of a biologics
license application for NeoCart. We wish to acknowledge and
thank the patients and investigators who participated in the trial
and shared their positive experiences with NeoCart,” stated Mr.
Gridley.
The NeoCart Phase 3 clinical trial is believed
to be the largest and first prospectively designed, randomized
clinical trial in North America evaluating the safety and efficacy
of a restorative cell therapy to treat knee cartilage damage.
It is also believed to be the only trial with a dual threshold
responder analysis endpoint. As part of the prospective data
analysis, Histogenics collected a variety of patient reported
outcome endpoints, including all measures of the Knee Injury and
Osteoarthritis Outcomes Score (KOOS) and the International Knee
Documentation Committee (IKDC) score, which are validated,
patient-centered assessments of pain and function that are commonly
used in current clinical trials of cartilage therapies. On
all but one of these measures, two of which are being utilized as
primary endpoints in ongoing clinical trials by third parties in
the U.S. for other therapies, NeoCart demonstrated statistically
significant superiority versus microfracture at one and two
years.
The Phase 3 clinical trial is the first study
prospectively enrolled consistent with current U.S. Food and Drug
Administration (FDA) guidance, which provides for the use of
microfracture as a comparator treatment in trials to repair knee
cartilage damage. The published FDA guidance also
specifically calls for a study population that, given the clinical
limitations and variable results of microfracture, we believe
provides more favorable results than what is typically seen in
microfracture in both the literature and a real-world
setting.
“We are pleased with the overall performance of
NeoCart in this Phase 3 clinical trial and the data confirm the
feedback we have received from several of the investigators who
participated in the trial. Most importantly, patients treated
with NeoCart displayed an early and sustained recovery from pain
and return to function that was clinically meaningful. The
data from this trial are also consistent with results seen in prior
clinical trials of NeoCart as well as the biomechanical data
generated as part of our collaboration with Cornell University,”
said Lynne Kelley, M.D., Chief Medical Officer of
Histogenics. “While we are continuing to analyze the data, we
have already seen a number of important results, including a
statistically significant improvement of NeoCart compared to
microfracture in lesion sizes of greater than 2 cm and patients
with higher body mass index. We think that results such as
these will be an important part of our planned discussions with the
FDA, as well as with clinicians if NeoCart is approved,” continued
Dr. Kelley.
There are approximately 1.2 million arthroscopic
procedures conducted each year to treat knee cartilage defects in
the U.S., with less than half of eligible patients currently
electing to receive treatment. Based on the data generated to
date, NeoCart may offer many of these patients a safe and effective
alternative, subject to FDA approval.
“As a physician who treats patients with knee
cartilage damage, I am keenly aware of the limitations of current
treatment approaches for this common and underserved condition,”
said David C. Flanigan, MD Associate Professor, Department of
Orthopedics, Director, Cartilage Restoration Program at The Ohio
State University Wexner Medical Center, and a high-enrolling
investigator in the Phase 3 clinical trial. “The pain and
loss of function associated with uncorrected knee cartilage lesions
can significantly limit these patients’ ability to maintain their
daily routines and often leads to other more serious comorbidities
over time. The rapid recovery for patients who received this
cartilage tissue implant compared to those who underwent
microfracture indicates that implants, such as NeoCart, may be an
attractive alternative for patients seeking a better quality of
life and faster return to function,” continued Dr.
Flanigan.
The primary endpoint for the Phase 3 clinical
trial was a dual-threshold responder analysis measuring the
improvement in KOOS pain and IKDC function scores for each patient
treated with NeoCart compared to those treated with microfracture
one year after the time of treatment. Dual-threshold
responders were defined as patients who, relative to their baseline
measurements, had at least a 12-point improvement in the KOOS pain
sub-score assessment and a 20-point improvement in the IKDC
subjective assessment. The trial also evaluated additional
pain, quality of life, and function outcomes using all five
measures of KOOS subscales, including Sports and Recreation.
The change from baseline and the relative change between the
NeoCart and microfracture arms was also measured at one year which
contrasts with clinical trials of other products, either on the
market or in development, that measured these changes at two years.
Efficacy and safety will continue to be followed out to three
years, and Histogenics expects to further track patients for future
planned analyses, including patients from prior clinical trials who
received a NeoCart treatment.
Demographics for both study arms were similar
and represent a patient population that was intended to ensure that
microfracture would respond favorably, including patients with an
average age of approximately 39 years old and a Body Mass Index
(BMI) of approximately 27. Furthermore, the mean lesion size
was 2.1 cm in the NeoCart arm and 1.8 cm in the microfracture
arm. There were no other significant differences between the
treatment arms.
The results with respect to the primary endpoint
(dual threshold responder analysis one year after treatment) are
summarized below:
|
|
|
|
|
|
NeoCart |
Microfracture |
|
|
|
Positive
Responders |
Responder
Rate |
Positive
Responders |
Responder
Rate |
Difference |
|
ITT |
121/170 |
71.2% |
49/79 |
62.0% |
9.2 |
p=0.1877 |
mITT |
121/163 |
74.2% |
49/79 |
62.0% |
12.2 |
P=0.0714 |
As Treated |
120/162 |
74.1% |
50/80 |
62.5% |
11.6 |
p=0.0735 |
Per Protocol |
118/155 |
76.1% |
43/65 |
66.2% |
10.0 |
p=0.1362 |
|
|
|
|
|
|
|
Key additional findings from the clinical trial
include:
NeoCart demonstrated statistically significant
improvements in pain and function at both one and two years after
treatment as measured by changes in the KOOS and IKDC scores.
|
KOOS pain score (mITT Population) |
Change from Baseline |
(NeoCart Baseline = 54.0; Microfracture
Baseline = 52.4) |
|
NeoCart |
Microfracture |
|
Visit |
N |
Mean |
N |
Mean |
P-Value |
3-months |
160 |
24.1 |
75 |
22.4 |
0.0487* |
6-months |
157 |
28.6 |
75 |
27.0 |
0.0819 |
1-year |
158 |
31.4 |
72 |
28.7 |
0.0239* |
2-years |
87 |
32.2 |
34 |
28.9 |
0.0080* |
3-years |
39 |
34.3 |
16 |
30.7 |
0.1071 |
*
Statistically significant |
|
|
|
|
|
IKDC subjective knee exam score (mITT
Population) |
Change from Baseline |
(NeoCart Baseline = 40.3; Microfracture
Baseline = 40.0) |
|
NeoCart |
Microfracture |
|
Visit |
N |
Mean |
N |
Mean |
P-Value |
3-months |
159 |
13.7 |
76 |
14.5 |
0.9686 |
6-months |
156 |
24.4 |
74 |
22.4 |
0.1572 |
1-year |
158 |
33.1 |
71 |
28.3 |
0.0126* |
2-years |
87 |
35.3 |
34 |
30.2 |
0.0366* |
3-years |
38 |
39.9 |
16 |
32.6 |
0.2691 |
*
Statistically significant |
|
|
|
|
|
|
|
|
|
|
|
NeoCart, the most advanced therapy from
Histogenics restorative cell therapy platform, is functional
cartilage that combines breakthroughs in bio-engineering,
biomaterials and cell processing to enhance the autologous
cartilage repair process. NeoCart, which is one of the most
rigorously studied restorative cell therapies for orthopedic use,
merges a patient’s own cells with a fortified three-dimensional
scaffold designed to accelerate healing and reduce pain.
NeoCart’s ability to function like cartilage at the time of
treatment may enable patients to return to work and daily
activities more rapidly than currently available treatment options
such as microfracture.
Histogenics is in the process of requesting a
meeting with the FDA to discuss the data and a potential BLA
submission. In addition, Histogenics intends to present the
complete study results at upcoming medical conferences and will
seek to have the data published in one or more peer reviewed
journals.
Conference Call and Webcast
Information
Histogenics management will host a conference
call on Wednesday, September 5, 2018 at 8:30am EDT. A
question-and-answer session will follow Histogenics’ remarks.
To participate on the live call, please dial (877) 930-8064
(domestic) or (253) 336-8040 (international) and provide the
conference ID 8764946 five to ten minutes before the start of the
call.
To access a live audio webcast of the
presentation on the “Investor Relations” page of the Histogenics
website, please click here. A replay of the webcast will be
archived on Histogenics’ website for approximately 60 days
following the presentation.
About Histogenics
Corporation
Histogenics (Nasdaq: HSGX) is a leader in
the development of restorative cell therapies that may offer
rapid-onset pain relief and restored function. Histogenics’
lead investigational product, NeoCart, is designed to rebuild a
patient’s own knee cartilage to treat pain at the source and
potentially prevent a patient’s progression to
osteoarthritis. NeoCart is one of the most rigorously studied
restorative cell therapies for orthopedic use. NeoCart is
designed to perform like articular hyaline cartilage at the time of
treatment, and as a result, may provide patients with more rapid
pain relief and accelerated recovery as compared to the current
standard of care. Histogenics’ technology platform has the
potential to be used for a broad range of additional restorative
cell therapy indications. For more information on Histogenics
and NeoCart, please visit www.histogenics.com.
Forward-Looking Statements
Various statements in this release are
“forward-looking statements” under the securities laws. Words
such as, but not limited to, “anticipate,” “believe,” “can,”
“could,” “expect,” “estimate,” “design,” “goal,” “intend,” “may,”
“might,” “objective,” “plan,” “predict,” “project,” “target,”
“likely,” “should,” “will,” and “would,” or the negative of these
terms and similar expressions or words, identify forward-looking
statements. Forward-looking statements are based upon current
expectations that involve risks, changes in circumstances,
assumptions and uncertainties.
Important factors that could cause actual
results to differ materially from those reflected in Histogenics’
forward-looking statements include, among others: NeoCart’s
potential as a treatment for knee cartilage damage; expectations
regarding the timing and success of discussions with the FDA
regarding the submission of a biologics license application for
NeoCart; the timing, associated expenses and ability to obtain and
maintain regulatory approval of NeoCart or any product candidates,
and the labeling for any approved products; the market size and
potential patient population in markets where Histogenics’ and its
partners expect to compete; updated or refined data based on
Histogenics’ continuing review and quality control analysis of
clinical data; the scope, progress, timing, expansion, and costs of
developing and commercializing Histogenics’ product candidates; the
ability to obtain and maintain regulatory approval regarding the
comparability of critical NeoCart raw materials following its
technology transfer and manufacturing location transition;
Histogenics’ expectations regarding its expenses and revenue;
Histogenics’ ability to obtain additional debt or equity capital
and other factors that are described in the “Risk Factors” and
“Management’s Discussion and Analysis of Financial Condition and
Results of Operations” sections of Histogenics’ Annual Report on
Form 10-K for the year ended December 31, 2017 and Quarterly Report
on Form 10-Q for the quarter ended June 30, 2018, which are on file
with the SEC and available on the SEC’s website at
www.sec.gov. In addition to the risks described above and in
Histogenics’ Annual Report on Form 10-K and Quarterly Reports on
Form 10-Q, Current Reports on Form 8-K and other filings with the
SEC, other unknown or unpredictable factors also could affect
Histogenics’ results.
There can be no assurance that the actual
results or developments anticipated by Histogenics will be realized
or, even if substantially realized, that they will have the
expected consequences to, or effects on, Histogenics.
Therefore, no assurance can be given that the outcomes stated in
such forward-looking statements and estimates will be achieved.
All written and verbal forward-looking
statements attributable to Histogenics or any person acting on its
behalf are expressly qualified in their entirety by the cautionary
statements contained or referred to herein. Histogenics
cautions investors not to rely too heavily on the forward-looking
statements Histogenics makes or that are made on its behalf.
The information in this release is provided only as of the date of
this release, and Histogenics undertakes no obligation, and
specifically declines any obligation, to update or revise publicly
any forward-looking statements, whether as a result of new
information, future events or otherwise.
Contacts:
Investor Relations:
Tel: +1 (781) 547-7909
InvestorRelations@histogenics.com
Media Relations:
Glenn Silver, Lazar Partners Ltd.
Tel: + 1 (646) 871-8485
gsilver@lazarpartners.com
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