Full Press Release Details
Tonix Pharmaceuticals Holding Corp. 8-K
Tonix Pharmaceuticals Announces Topline Results
from Phase 2 PREVAIL Proof-of-Concept Study of TNX-102 SL for the Management of Fibromyalgia-Type Long COVID
TNX-102 SL showed a robust effect size of
0.5 in improving fatigue and showed consistent activity across secondary measures of sleep quality, cognitive function, disability and
Patient Global Impression of Change, but did not meet the primary endpoint of multi-site pain reduction at week 14
Findings fulfill the objectives of this proof-of-concept
study, supporting the decision to advance the program based on a proposed primary endpoint using the PROMIS Fatigue scale
Tonix plans to meet with FDA to discuss a
path to registration; fatigue is the signature symptom of Long COVID and the principal symptom overlapping with CFS/ME and fibromyalgia
CHATHAM, N.J., September 5, 2023 - Tonix
Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a biopharmaceutical company with marketed products and a pipeline
of development candidates, today announced topline results from the Phase 2 proof-of-concept PREVAIL study of TNX-102 SL 5.6 mg for the
management of fibromyalgia-type Long COVID. TNX-102 SL treatment showed a robust effect size (ES) in improving fatigue and showed consistent
activity trending to improvements across the secondary endpoints of sleep quality, cognitive function, disability and patient global impression
of change (PGIC). TNX-102 SL trended towards improvement but did not achieve the pre-specified primary endpoint of improving Long COVID
pain intensity scores at Week 14. The proposed mechanism of TNX-102 SL is improving sleep quality, which NIH recently announced is a target
of future RECOVER clinical trials in Long COVID, a National Institute of Health (NIH) research program designed to understand, treat,
and prevent long COVID.1,2 There is currently no approved drug for the treatment of Long COVID.
PREVAIL was a randomized, double-blind, placebo-controlled,
multi-site proof-of-concept study of 63 patients with laboratory-documented COVID-19 illness preceding Long COVID. PREVAIL was designed
and conducted to guide the design of registrational studies of TNX-102 SL in fibromyalgia-type Long COVID. TNX-102 SL was generally well
tolerated with an adverse event (AE) profile comparable to prior studies with TNX-102 SL. AE-related discontinuations were similar in
drug and placebo arms. No new safety signals were observed.
"The robust activity of TNX-102 SL on
the PROMIS Fatigue scale3-5 (ES=0.5, Figure 4) is important because patients and experts view fatigue as the signature symptom
of Long COVID and it has been identified as the dominant symptom contributing to disability,"6 said Dr. Seth Lederman,
President and CEO of Tonix Pharmaceuticals. "In addition, TNX-102 SL showed consistent trends toward improvement in sleep quality,
cognitive function, disability and the PGIC responder rate for TNX-102 SL compared to placebo (Figure 5) at week 14 (34.4% vs. 16.1%,
difference=18.2%). Together, these findings fulfill the objectives of this proof-of-concept study in supporting the decision to advance
the program based on a proposed primary endpoint using the PROMIS Fatigue scale."
The Company intends to request an End-of-Phase
2 meeting with the U.S. Food and Drug Administration (FDA) to discuss a potential Phase 3 program based on a proposed primary outcome
measure using the PROMIS Fatigue scale. The meeting is expected to take place in the first quarter of 2024. Fatigue is the symptom of
Long COVID that principally overlaps with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and fibromyalgia. In the NIH funded
RECOVER study analysis, fatigue was the top featured symptom and is common in each of the four clusters.7
"The data from PREVAIL reinforce our
belief in TNX-102 SL as a potential bedtime medicine for the management of fibromyalgia-type Long COVID," said Gregory Sullivan,
M.D., Chief Medical Officer of Tonix Pharmaceuticals. "We believe the PREVAIL trial results will help guide the next phase of development
for TNX-102 SL, supporting the design of a potential registrational trial for fibromyalgia-type Long COVID based on PROMIS fatigue as
a primary endpoint, pending review and feedback from the FDA. In both of our prior Phase 3 studies of TNX-102 SL 5.6 mg in fibromyalgia,
we observed numerical improvement in the PROMIS fatigue score (in RELIEF p=0.007
MMRM8 and in RALLY p=0.007 MMRM9)."
Dr. Sullivan continued, "Although the
validity of PROMIS Fatigue is not yet established in Long COVID, we believe the results of PREVAIL, together with extensive data from
studies in other chronic conditions3-5 - including Tonix's studies in fibromyalgia - make PROMIS Fatigue
a solid candidate for the primary endpoint of future Long COVID registrational studies. We look forward to an anticipated End-of-Phase
2 meeting with the FDA to discuss these data and expect to present full data from PREVAIL in a peer-reviewed format and at upcoming medical
conferences. Together, we believe these findings support the recognition of fibromyalgia-type Long COVID as a clinically meaningful subgroup
of Long COVID patients and underscore the potential of TNX-102 SL as a once daily, oral therapy for this debilitating condition. We are
grateful to the patients and their families and supporters, who participated in this study."
Key Phase 2 PREVAIL Study Results
In the study, 63 subjects were enrolled and
randomized 1:1 across approximately 30 U.S. sites to receive either TNX-102 SL or placebo daily at bedtime for 14 weeks. Subjects started
with TNX-102 SL 2.8 mg tablet or one placebo tablet for the first 2 weeks and then increased to TNX-102 SL 5.6 mg (2 x 2.8 mg tablets)
or two placebo tablets for the remaining 12 weeks of the treatment period. The percentage of subjects completing the study was 81.3% in
the TNX-102 SL group and 80.6% in the placebo group. Demographics and baseline characteristics are shown in Table 1.
SL demonstrated a favorable safety and tolerability profile over 14 weeks of treatment with no new safety signals. The most common adverse
events are shown in Table 2. Participants with at least one treatment-emergent adverse event (TEAE) were at a rate of 56.3% on
TNX-102 SL and 38.7% on placebo. In the TNX-102 SL group, 6.3% discontinued due to TEAE compared to 9.7% on placebo. Only one TEAE in
the study was rated as severe, gastritis in a participant in the TNX-102 SL group. There were no serious adverse events (SAEs) in the
Abbreviations: LS, least squares; SE, standard error
Abbreviations: LS, least squares; SE, standard error
Abbreviations: LS, least squares; SE, standard error;
SD, sleep disturbance
Abbreviations: LS, least squares; SE, standard error
About the Phase 2 PREVAIL Study
The Phase 2 PREVAIL proof-of-concept study
was a 14-week double-blind, randomized, multicenter, placebo-controlled study to evaluate the efficacy and safety of TNX-102 SL taken
daily at bedtime in patients with multi-site pain associated with laboratory-documented post-acute sequelae of SARS-CoV-2 infection (PASC).
The trial was conducted at approximately 30 sites in the U.S. The primary efficacy endpoint is the change from baseline in the weekly
average of daily self-reported worst pain intensity scores at the Week 14 endpoint. Key secondary efficacy endpoints include change from
baseline in self-reported scores for sleep disturbance, fatigue, cognitive function and PGIC.
For more information, see ClinicalTrials.gov
Identifier: NCT05472090.
About Long COVID or Post-Acute Sequelae
Post-acute sequelae of COVID-19, or PASC is
the formal name for a condition now widely known as Long COVID. The U.S. Department of Health and Human Services (HHS) recently estimated
that 7.7 million to 23 million Americans have developed Long COVID and announced the formation of the "Office of Long COVID Research and Practice" to lead the
Long COVID response and coordinate efforts across the federal government. 10 Although most people recover from COVID-19
within weeks of the acute illness, a substantial portion develops a chronic syndrome called Long COVID.11 These individuals
experience a constellation of disabling symptoms long past the time of recovery from acute COVID-19. Most Long COVID patients who have
been studied appear to have cleared the SARS-CoV-2 infection from their systems. The symptoms of Long COVID can include fatigue, sleep
disorders, multi-site pain, fevers, shortness of breath, cognitive impairment described as "brain fog" or memory disturbance,
gastrointestinal symptoms, anxiety, and depression. According to the Centers for Disease Control and Prevention (CDC), 1 in 13 adults
in the U.S. (7.5%) have Long COVID symptoms.11 Long COVID is typically associated with moderate or severe COVID-19 but
can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. More than 40% of adults in the United States reported having
COVID-19 in the past, and nearly one in five of those (19%) are currently still having symptoms of Long COVID.11 Long
COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.12-15 In
response to the urgent need for therapies that address Long COVID, Congress awarded $1.15 billion to the National Institutes of Health
to study Long COVID in December 2020.16 The U.S. Department of Health and Human Services National Research Action
Plan on Long COVID17, released in August 2022, addresses the overlap of Long COVID with CFS/ME, which, like fibromyalgia,
is one of the overlapping chronic pain syndromes with central and peripheral sensitization.18 A published survey19 found
comparable pain, fatigue, and functional impairment between Long COVID, fibromyalgia, and CFS/ME. This symptom overlap between these conditions
has suggested that altered neurologic function is one of the leading hypotheses to explain them.20 While the vaccines
available in the U.S., through either FDA approval or under Emergency Use Authorization, have been shown to prevent acute COVID, their
ability to prevent Long COVID is unknown. There is currently no approved drug for the treatment of Long COVID.
About Fibromyalgia-Type Long COVID
Common symptoms of Long COVID, including multi-site
pain, fatigue, unrefreshing sleep, and cognitive dysfunction, or brain fog,' are hallmarks of conditions like fibromyalgia