Market Overview

Eagle Pharmaceuticals Concludes Enrollment of Second Safety and Efficacy Study at Hajj to Evaluate RYANODEX for Exertional Heat Stroke


--Preliminary Analysis: RYANODEX Provides Benefit for Patients--

--Eagle Plans to Meet with FDA to Discuss Next Steps--

Eagle Pharmaceuticals, Inc. ("Eagle" or "the Company") (NASDAQ:EGRX)
today announced completion of enrollment of the Company's second
clinical study to further evaluate the safety and efficacy of RYANODEX®
(dantrolene sodium for injectable suspension) for the treatment of
exertional heat stroke ("EHS"), an investigational new indication for
the product.

The randomized and double-blinded study was conducted at four Emergency
Departments in the Makkah region of Saudi Arabia during the 2018 Hajj
Season, which took place August 19-24, 2018. The study enrolled seven
severely ill EHS patients. Based on a preliminary analysis of the data,
EHS patients who received RYANODEX plus Standard of Care ("SOC"), which
consists of body cooling by physical methods and supportive measures,
showed an additive benefit compared to patients receiving cooling only.

The two treatment groups had comparable baseline characteristics,
including severe hyperthermia and severe neurological dysfunction.
Patients randomized to Group A (RYANODEX plus SOC) had a mean baseline
core body temperature of 107.8 °F and mean Glasgow Coma Scale (GCS)
score of 5. Similarly, patients in Group B (SOC only) had a mean core
body temperature of 107.2 °F and mean GCS score of 5 at baseline. A GCS
score of 5 represents severe brain injury.

Preliminary evaluation of the data show that of the four patients dosed
with RYANODEX, two had restoration of neurological functioning, and
another patient showed substantial improvement over the course of the
study. The fourth patient, who had an initial core body temperature of
112.1 °F, remained unchanged. In contrast, the SOC group had three
patients. One patient had restoration of neurological functioning, one
remained with severe impairment and one subject showed further
deterioration of neurological functioning.

This preliminary assessment is consistent with the data from the study
conducted in 2015, in which patients dosed with RYANODEX plus SOC showed
an additive benefit compared to patients receiving SOC only.

During the 2018 Hajj, overall emergency room visits were dramatically
decreased from previous years due to well-implemented crowd management,
lower temperatures, lower humidity and other external factors. As a
result, the number of EHS patients available for study enrollment was
also significantly less than in previous years, and therefore much lower
than anticipated. The Company intends to complete the analysis of the
data and meet with the U.S. Food and Drug Administration ("FDA") to
discuss next steps.

"Our preliminary evaluation of the data indicates that the patients
receiving RYANODEX showed an improved outcome compared to patients
treated with cooling only. We have now conducted two randomized,
controlled studies and have obtained comparable results in both studies.
We have 41 subjects for a rare disease with FDA fast-track and Orphan
Drug designations, and no other approved drugs to treat EHS," stated
Scott Tarriff, Chief Executive Officer.

"Based upon the collective results of our two clinical trials as well as
other work performed by the Company and researchers around the world, we
believe there is sufficient data to provide evidence of safety and
efficacy for the use of RYANODEX for the treatment of EHS. We plan to
meet with the FDA to discuss the next steps in making this very
important product available to those afflicted with exertional heat
stroke," concluded Tarriff.

This study was conducted in compliance with all current FDA regulations
and is the second trial conducted by Eagle. The study intended to
provide confirmatory evidence of the Company's initial safety and
efficacy study of RYANODEX for EHS conducted in September 2015 and to
satisfy the FDA's requirements to amend Eagle's original NDA.

Additional details about the study can be found at
( Identifier: NCT03600376).

Results of 2015 Study

Eagle's initial study was conducted from September 22-27, 2015, at the
Emergency Departments of four hospitals during the Hajj pilgrimage in
the Makkah region, Saudi Arabia.

The open-label, randomized, 2-arm study was primarily designed to assess
the change in the level of neurological impairment in subjects suffering
from the symptoms of EHS, from baseline to 90 minutes
post-randomization, using the Glasgow Coma Scale ("GCS").

The use of a validated and well-known instrument to evaluate
neurological functioning, such as the Glasgow Coma Scale, provides a
reliable assessment of CNS impairment and its progression over time.

The study enrolled 34 EHS patients between 18-45 years of age.

Subjects were randomized 1:1 into two groups to receive either RYANODEX
plus SOC, (Group A, n=17), or SOC alone (Group B, n=17).

Per study protocol, all subjects experienced exertional physical
activity within the previous 24 hours, and demonstrated hallmark
clinical features of EHS, including:

  • Presence of neurological impairment, evaluated using the Glasgow Coma
    Scale ("GCS");
  • Baseline core body temperature of 104° F (40° C) or greater; and,
  • Tachycardia (at least 100 heart beats per minute)

Baseline disease characteristics were comparable between the two groups,
including a mean GCS score (Group A: 6.1 vs. Group B: 5.9) representing
severe neurological impairment, and severe hyperthermia (Group A: 106.5°
F (41.4° C) vs. Group B: 106.7° F (41.5° C).


Patients were evaluated at baseline and at regular time intervals
post-randomization for changes in level of consciousness using GCS, and
core body temperature.

Study results showed that a greater proportion of patients treated with
Ryanodex plus SOC exhibited a clinically meaningful improvement in their
neurological functioning (GCS ≥ 13) within 90 minutes (29.4%) and within
24 hours post-randomization (47.1%), compared with SOC only-treated
subjects (11.8% and 23.5%, respectively).

In addition, pre-specified odds ratio analysis showed that odds of
achieving a GCS score ≥ 13 within 90 minutes postrandomization was about
3 times greater for subjects in the Ryanodex plus SOC group than for
subjects who received SOC-only and remained almost unchanged at or prior
to 24 hours postrandomization. Also, the median time to reach first
rectal temperature ≤ 38°C was shorter in the Ryanodex plus SOC group
(90.0 minutes) than in the SOC only group (103.0 minutes).


Overall, safety findings were comparable between the two study groups,
and there were no serious drug-related adverse events. Fewer patients
experienced treatment-emergent adverse events in Group A (64.7%), as
compared to Group B (76.5%), and the incidence of serious adverse events
in each of the two treatment arms was comparable. In summary, the safety
results of the study are consistent with the known, and well
characterized, safety profile of RYANODEX.

About the Glasgow Coma Scale

The Glasgow Coma Scale ("GCS") is a validated tool that functions as a
common scoring system among medical practitioners for measuring and
describing the varying degrees of level of consciousness in a person
following an acute brain injury.1

Widely accepted as reliable and objective, this scoring system is used
by trained staff at the site of a potential brain injury, as well as in
emergency departments and intensive care units. The GCS was selected for
this study as an objective and accurate method to measure the state of
mental impairment and the subsequent improvement of test subjects.

The GCS measures three key functions: Eye Opening, Motor Response and
Verbal Response.

Eye Opening (E)

4 = spontaneous

3 = to voice

2 = to pain

1 = none

Motor Response (M)

6 = normal

5 = localized to pain

4 = withdraws to pain

3 = decorticate posture (an abnormal posture that can include
rigidity, clenched fists, legs held straight out, and arms bent
inward toward the body with the wrists and fingers bend and held
on the chest)

2 = decerebrate (an abnormal posture that can include rigidity,
arms and legs held straight out, toes pointed downward, head and
neck arched backwards)

1 = none

Verbal Response (V)

5 = normal conversation

4 = disoriented conversation

3 = words, but not coherent

2 = no words, only sounds

1 = none


1Teasdale G, Jennett B. (1974). "Assessment of coma and
impaired consciousness. A practical scale." Lancet 13 (2): 81–4.

Clinicians use the GCS to assess the eye opening response, the verbal
response, and the motor response in patients with an impaired level of
consciousness. The total GCS score is the sum of the scores for each of
these functions, classified as follows2:

Classification       Total Glasgow Coma Scale Score
Severe       3 – 8
Moderate       9 – 12
Mild       13 – 15

About Exertional Heat Stroke

The two types of heat stroke – classical and exertional - are the most
severe forms of heat illness. Classical heat stroke often results from
passive exposure to heat, as observed during heat waves, and mostly
affects very young and elderly people. In contrast, EHS is a rare
disease, mostly impacting young - otherwise healthy - people, performing
intense physical activity in hot weather environments. EHS is a
life-threatening and unpredictable condition, characterized by an acute
hyperthermic-hypermetabolic status, which may result in severe
neurological, renal and liver damage, or even death, if not treated
promptly. Currently, the treatment of EHS is limited to body surface
cooling and supportive measures; despite the use of cooling, up to 30%
of EHS victims suffer long-term neurological sequelae.


RYANODEX® (dantrolene sodium) for injectable suspension is indicated for
the treatment of malignant hyperthermia in conjunction with appropriate
supportive measures, and for the prevention of malignant hyperthermia in
patients at high risk.

Important Safety Information

RYANODEX® is not a substitute for appropriate supportive measures in the
treatment of malignant hyperthermia, including:

Discontinuing triggering anesthetic agents

Increasing oxygen

Managing the metabolic acidosis

Instituting cooling when necessary


2 "What Is the Glasgow Coma Scale?",
n.d. Web. <>.


Administering diuretics to prevent late kidney injury due to
myoglobinuria (the amount of mannitol in RYANODEX® is insufficient to
maintain diuresis).

Precautions should be taken when administering RYANODEX® preoperatively
for the prevention of malignant hyperthermia, including monitoring vital
signs, avoiding known triggering agents, and monitoring for early
clinical and metabolic signs of malignant hyperthermia that may indicate
additional treatment is needed.

The administration of dantrolene sodium is associated with loss of grip
strength and weakness in the legs, as well as drowsiness, dizziness,
dysphagia, dyspnea, and decreased inspiratory capacity. Patients should
not be permitted to ambulate without assistance until they have normal
strength and balance. Care must be taken to prevent extravasation of
RYANODEX® into the surrounding tissue due to the high pH of the
reconstituted RYANODEX® suspension and potential for tissue necrosis.

RYANODEX® full Prescribing Information can be found at

About Eagle Pharmaceuticals, Inc.

Eagle is a specialty pharmaceutical company focused on developing and
commercializing injectable products that address the shortcomings, as
identified by physicians, pharmacists and other stakeholders, of
existing commercially successful injectable products. Eagle's strategy
is to utilize the FDA's 505(b)(2) regulatory pathway. Additional
information is available on the company's website at

Forward-Looking Statements

This press release contains forward-looking information within the
meaning of the Private Securities Litigation Reform Act of 1995, as
amended and other securities laws. Forward-looking statements are
statements that are not historical facts. Words such as "will,"
"continue," "may," "believe," "intends," "anticipate(s)," "plan,"
"enables," "potentially," "entitles," and similar expressions are
intended to identify forward-looking statements. These statements
include statements regarding future events including, but not limited
to: the safety and efficacy of RYANODEX for the treatment of EHS; FDA
approval of the use of RYANODEX for the treatment of EHS; the timing and
level of success of a future launch of RYANODEX; successful compliance
with FDA and other governmental regulations applicable to manufacturing
facilities, products and/or businesses; the commercial success of
Eagle's commercial portfolio, including RYANODEX, if and when launched;
and other factors that are discussed in Eagle's Annual Report on Form
10-K for the year ended December 31, 2017, and its other filings with
the U.S. Securities and Exchange Commission. All of such statements are
subject to certain risks and uncertainties, many of which are difficult
to predict and generally beyond Eagle's control, that could cause actual
results to differ materially from those expressed in, or implied or
projected by, the forward-looking information and statements. Such risks
include, but are not limited to: whether the FDA will ultimately approve
RYANODEX for the treatment of EHS; whether Eagle's studies will support
the safety and efficacy of RYANODEX for the treatment of EHS; whether
Eagle's management and/or board of directors will be effective in
managing Eagle's business, future growth and market protection,
including with respect to RYANODEX; whether Eagle will maintain
successful compliance with the FDA and other governmental regulations;
and other risks described in Eagle's filings with the U.S. Securities
and Exchange Commission. Readers are cautioned not to place undue
reliance on these forward-looking statements that speak only as of the
date hereof, and we do not undertake any obligation to revise and
disseminate forward-looking statements to reflect events or
circumstances after the date hereof, or to reflect the occurrence of or
non-occurrence of any events.

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