Sorrento Therapeutics, Inc. (NASDAQ: SRNE, "Sorrento") released
positive Phase 1b trial data (clinicaltrials.gov NCT03542838) of
resiniferatoxin (RTX) with completed Day 84 effectiveness data
(end-point analysis) for all patients and completed six-month
follow-ups in all doses for all patients enrolled, with no negative
safety signal as of September 2020.
Dr. David Leiman, MD, a board certified
anesthesiologist, Clinical Assistant Professor of Surgery,
University of Texas at Houston, Director of Chronic Pain at Lotus
Clinical Research in Houston, Texas and lead investigator for this
clinical trial, commented, “RTX is a promising new treatment that
fits a clear unmet need for osteoarthritis patients, particularly
when traditional pain management options are insufficient or come
with significant drawbacks such as those encountered with opioids.
After participating in this trial and interacting with treated
patients, I am looking forward to the day RTX might be approved as
it would be another much needed tool in my specialty to help
address difficult to control pain.”
The Phase 1b trial was a placebo controlled
ascending dose study with an open-label extension to assess the
safety and preliminary efficacy of intra-articular administration
of RTX or saline control (as placebo group) for the treatment of
moderate to severe pain due to osteoarthritis (OA) of the knee. It
was expanded into a dose confirmation cohort to validate the safety
and efficacy of the selected therapeutic dose compared to the
individual’s baseline.
An abstract presenting intermediate data was
accepted for the OsteoArthritis Research Society International
(OARSI) meeting which was to be held in May 2020. The meeting was
cancelled due to COVID-19 restrictions. The abstract has now been
released from embargo and can be accessed on the conference website
(OARSI Conference Posters) under #197 on page S138.
These strong results have prompted the Company
to rapidly advance the investigational drug product into a Phase 2
clinical trial (against active drug and saline control) expected to
start in 2020 and a subsequent Phase 3 clinical trial expected to
start in 2021 after completing additional enabling preclinical
studies.
Updated Safety Outcome (primary end-point)
Ten subjects received a single saline-control
injection and 84 subjects received a single RTX injection. The
majority of subjects (N=50) were dosed with resiniferatoxin at 12.5
µg. No dose limiting toxicities were observed in any of the 84
subjects dosed with RTX at any dose level studied.
Treatment-emergent adverse events (TEAEs) were
expected based on the mechanism of action of the drug and included
post-injection pain, tachycardia and hypertension; all of which
resolved in less than a day. Mild to moderate post-procedural pain
was reported as expected in nearly all subjects dosed with RTX (as
well as in subjects treated with saline control) and was managed
with analgesics. The pain from drug administration typically
subsided within a few hours. No special requirements such as knee
cooling or local anesthetics application have been used in this
study.
Table 1: Subjects
with Treatment-Emergent Adverse Events in Study
PTVA-OA-001
TEAE Category |
Subjects dosed with RTX(N=84) |
Subjects dosed with saline control(N=10) |
Any TEAE |
83 (98.8%) |
8 (80.0%) |
Any Moderate TEAE |
42 (50%) |
1 (10.0%) |
Any Severe TEAE |
5 (6%) |
0 |
Any Life-Threatening or Fatal TEAE |
0 |
0 |
Any Serious TEAE |
7 (8.3%) |
0 |
Any TEAE considered related to study treatment |
77 (91.7%) |
7 (10.0%) |
Any Severe TEAE considered related to study treatment |
1 (1.2%) |
0 |
Any Serious TEAE considered related to study treatment |
0 |
0 |
Updated Efficacy Outcomes (secondary
end-point)
The magnitude of the difference in the treatment
effect versus saline control (as placebo used in the ascending dose
portion of the study) at 12 weeks exceeded what is traditionally
considered sufficient to support regulatory approval based on
greater than 2 points reduction in the WOMAC A1 10-point scale
question “pain at walking on flat surface” compared to placebo.
In the RTX dose selected for upcoming clinical
trials (12.5 ug), the WOMAC A1 score at day 84 showed an average of
a 4.92-point reduction relative to baseline for RTX, and an average
2.59-point reduction relative to the saline control (placebo).
Fast relief (less than a week) and durability of
the effect (over 84 days) confirm the clinical potential of the
drug for long-term control of pain associated with OA of the
knee.
The study was designed to follow patients to day
84. Patients were also given the option to be followed for a longer
period of time. RTX treated patients with good initial response who
were evaluated at day 168 showed pain relief to levels equivalent
to their D84 response (likely persistence of effect).
Exploratory end-points: Advanced disease (Kellgreen-Lawrence
Grade 3 and 4) and Womac A+C Composite Score
No difference in efficacy response was found
regardless of the degree of measured OA in patients
(Kellgren-Lawrence Grade 2, 3 or 4), suggesting that the strength
and duration of pain relief observed following RTX treatment in
this Phase 1b study may also be expected in a larger population of
patients with advanced OA.
To confirm the potential of RTX to benefit
patients waiting for total knee replacements, an analysis was
performed applying a composite score (Womac A plus Womac C) that is
traditionally used to assess a patients “qualification” for knee
replacement (see Table 2).
Patients who could qualify for total knee
replacement (Womac A + C over 23) showed a clear improvement
following treatment (68% improved by at least 20%, versus 20% in
the control group). The effect (see Figure 2) was sustained for at
least 84 days with a signal that did not seem to degrade at day 84.
Many patients followed through day 168 or day 365 indicate the
potential of the drug effect to persist in responders for 6 months
or more. These numbers, although encouraging, need to be confirmed
in trials with a larger number of patients (such as Sorrento’s
proposed Phase 2 and 3 trials).
Table 2:
Responder*
Analysis at Day 84 (Week 12). Subjects with Baseline Combined WOMAC
A Pain Subscale and WOMAC C Function Subscale >=23
Parameter |
Response |
12.5 ug RTX (in 5ml) |
Saline Control |
WOMAC Pain/Function |
>=20% Improvement |
34/50 (68.0%) |
2/10 (20.0%) |
* Responder defined as combined score for WOMAC
A Pain Subscale and WOMAC C Function Subscale with at least a 20%
decrease from baseline at Day 84 (Week 12). Note: Subjects without
Day 84 data were included as Non-Responders.
Sorrento has confirmed it will be pursuing RTX
for treatment of OA pain following a traditional development
program, but based on the positive results of this Phase 1b trial
will also add studies focusing on demonstrating the value of RTX as
an alternative to TKR surgery.
About Resiniferatoxin (RTX)
A thousand times “hotter” than pure capsaicin
(16 Billion Scoville units versus 16M), and with a high affinity
for afferent sensory pain nerves, resiniferatoxin binds to TRPV1
receptors present and selectively ablates the nerve endings
responsible for pain signals experienced by patients1. Delivered
peripherally (into the joint space) the transient nerve ending
ablation effect can have profound clinical benefits lasting for
months to years (as shown in canine studies2).
PTVA-OA-001 was a multicenter,
placebo-controlled Phase 1b study to assess the safety and define
the maximally tolerated dose of resiniferatoxin administered in the
knee joint in patients with moderate to severe pain associated with
osteoarthritis of the knee. The study was a dose-escalation
trial in which cohorts of patients received increasing doses of
resiniferatoxin until the maximum tolerated dose (MTD) was
achieved. The primary objective of the study was to evaluate the
safety of resiniferatoxin and identify the recommended dose for
Phase 3 trials. The secondary objective was to assess the
preliminary efficacy of resiniferatoxin measured by assessing
changes in the intensity of pain using the A1 score from the WOMAC
Index, a widely used proprietary validated pain questionnaire.
More information on this trial can be found at
www.clinicaltrials.gov (NCT03542838).
Information on upcoming Phase 3 trials (Total
Knee Replacement Surgery Deferment Pain and Osteroarthritis Pain)
can be found under the trial references NCT04386980 and
NCT04044742.
About Sorrento Therapeutics, Inc.
Sorrento is a clinical stage, antibody-centric,
biopharmaceutical company developing new therapies to treat
cancers. Sorrento's multimodal, multipronged approach to fighting
cancer is made possible by its extensive immuno-oncology platforms,
including key assets such as fully human antibodies (“G-MAB™
library”), clinical stage immuno-cellular therapies (“CAR-T”,
“DAR-T”), antibody-drug conjugates (“ADCs”), and clinical stage
oncolytic virus (“Seprehvir®”, “Seprehvec™”). Sorrento is also
developing potential antiviral therapies and vaccines against
coronaviruses, including COVIDTRAP™, ACE-MAB™, COVI-MAB™,
COVI-GUARD™, COVI-SHIELD™ and T-VIVA-19™; and diagnostic test
solutions, including COVI-TRACK™ and COVI-TRACE™.
Sorrento's commitment to life-enhancing
therapies for patients is also demonstrated by our effort to
advance a first-in-class (TRPV1 agonist) non-opioid pain management
small molecule, resiniferatoxin (“RTX”), and ZTlido® (lidocaine
topical system) 1.8% for the treatment of post-herpetic neuralgia.
RTX has completed a Phase IB trial for intractable pain associated
with cancer and is completing a Phase 1B trial in osteoarthritis
patients. ZTlido® was approved by the FDA on February 28, 2018.
For more information visit www.sorrentotherapeutics.com
Forward-Looking Statements
This press release and any statements made for
and during any presentation or meeting contain forward-looking
statements related to Sorrento Therapeutics, Inc., under the safe
harbor provisions of Section 21E of the Private Securities
Litigation Reform Act of 1995 and subject to risks and
uncertainties that could cause actual results to differ materially
from those projected. Forward-looking statements include statements
regarding the expectations for Sorrento's and its subsidiaries'
technologies and product candidates, including, but, not limited
to, resiniferatoxin (RTX); the potency, potential pain relief
capabilities and potential duration of pain relief of RTX; the
expected optima intra-articular therapeutic dose of RTX for future
clinical trials; the safety and efficacy of RTX; the expected
timing for the last visit for the last patient follow-up (1 year);
the clinical potential of RTX; the ability of RTX to be an
alternative pain management option for control of refactory pain;
the expected commencement of any Phase 2 or Phase 3 trials for RTX;
the completion of additional enabling preclinical studies; ; the
potential impact of COVID-19 on elective surgeries, such as total
knee replacement for OA knee pain and potential future studies
focusing on demonstrating the value of RTX as an alternative to TKR
surgery. Risks and uncertainties that could cause our actual
results to differ materially and adversely from those expressed in
our forward-looking statements, include, but are not limited to:
risks related to Sorrento's and its subsidiaries' technologies and
prospects, including, but not limited to, RTX; risks related to
seeking regulatory approvals and conducting and obtaining results
of clinical trials, including, but not limited to, the PTVA-OA-001
study or trial and any prior RTX studies in animals; costs
associated with RTX clinical trials; risks that prior test, study
and trial results may not be replicated in future studies and
trials; the clinical and commercial success of RTX; the viability
and success of using RTX for treatments in certain therapeutic
areas, including OA; risks related to the global impact of
COVID-19; and and other risks that are described in Sorrento's most
recent periodic reports filed with the Securities and Exchange
Commission, including Sorrento's Annual Report on Form 10-K for the
year ended December 31, 2018, and subsequent Quarterly Reports on
Form 10-Q filed with the Securities and Exchange Commission,
including the risk factors set forth in those filings. Investors
are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date of this release and we
undertake no obligation to update any forward-looking statement in
this press release except as required by law.
Media and Investor Relations
Contact: Alexis Nahama, SVP Corporate Development and Head of
the RTX Program.
Telephone: 1.858.203.4120
Email: mediarelations@sorrentotherapeutics.com
###
Sorrento® and the Sorrento logo are registered
trademarks of Sorrento Therapeutics, Inc. G-MAB™, COVI-GUARD™,
COVI-SHIELD™, COVIDTRAP™, T-VIVA-19™, COVI-MAB™, ACE-MAB™,
COVI-TRACK™, and COVI-TRACE™ are trademarks of Sorrento
Therapeutics, Inc.
ZTlido® is a trademark owned by Scilex Pharmaceuticals Inc.All
other trademarks are the property of their respective owners.© 2020
Sorrento Therapeutics, Inc. All Rights Reserved.
1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC398431/2
Sorrento Therapeutics (Ark Animal Health) internal data (on
file)
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