INDIANAPOLIS, Sept. 30, 2021 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) and Incyte (NASDAQ: INCY) announced today
detailed results from two pivotal Phase 3 trials (BRAVE-AA1 and
BRAVE-AA2), which found once-daily OLUMIANT®
(baricitinib) 4-mg was superior to placebo in achieving significant
scalp hair regrowth as early as 24 weeks in adults with severe
alopecia areata (AA) as defined by ≥50% scalp hair loss at
baseline.
Significant improvements in scalp hair regrowth compared to
placebo were achieved at 36 weeks for patients taking OLUMIANT 2-mg
and 4-mg oral doses, as previously disclosed in topline findings
from BRAVE-AA1 and BRAVE-AA2 earlier this year. In both studies, a
greater proportion of patients taking OLUMIANT 4-mg compared to
placebo also achieved full regrowth or regrowth with minimal gaps
in coverage of eyebrow and eyelash hair at 36 weeks, which were key
secondary endpoints of the studies.
These results, along with safety data in adult patients with
moderate to severe atopic dermatitis (AD), are being presented
virtually at the 30th European Academy of Dermatology
and Venerology (EADV) Congress, taking place from Sept. 29-Oct. 2, 2021.
Alopecia areata is a widely misunderstood, autoimmune disease
that can cause extreme and patchy hair loss on the scalp, face and
other areas of the body, along with emotional distress and
psychosocial effects. OLUMIANT has received Breakthrough Therapy
designation from the U.S. Food and Drug Administration (FDA) for
the treatment of AA. Lilly plans to submit a supplemental New Drug
Application (sNDA) to the FDA for OLUMIANT in AA in the second half
of 2021.
OLUMIANT Demonstrated Improvement in Scalp, Eyelash and
Eyebrow Hair Regrowth in Patients with AA in Two Phase 3
Trials
In BRAVE-AA1 and BRAVE-AA2, the first completed, randomized,
double-blind, placebo-controlled Phase 3 trials for AA, 598 and 490
patients, respectively, underwent 36 weeks of treatment. Both
studies included adults with severe AA, defined as a Severity of
Alopecia Tool (SALT) score ≥50 (those with ≥50% scalp hair loss).
At baseline, the participants had a mean SALT score of 85.5 (85.5%
scalp hair loss, or 14.5% scalp hair coverage).
Across treatment groups, the average age of participants was
37.5 years old, and they had lived with AA for a mean of 12.2 years
since first experiencing symptoms, with the onset for hair loss
occurring at approximately age 25.
In BRAVE-AA1, statistically significant improvement in scalp
hair regrowth occurred as early as 16 weeks among patients treated
with OLUMIANT 4-mg and 24 weeks with OLUMIANT 2-mg, compared to
placebo. At 16 weeks, nearly 1 in 5 patients (18.5%, n=52) taking
OLUMIANT 4-mg achieved 80 percent or more scalp hair coverage (as
measured by a SALT score ≤20) as compared to placebo (4.2%, n=8,
p≤0.001). At 24 weeks, 1 in 10 patients (11.4%, n=21) taking
OLUMIANT 2-mg achieved 80% or more scalp hair coverage as compared
to placebo (4.8%, n=9, p=0.013).
In BRAVE-AA2, statistically significant improvement occurred as
early as 24 weeks for patients treated with OLUMIANT 4-mg, with
more than 1 in 4 patients (28.2%, n=66) reaching 80% or more scalp
hair coverage as compared to placebo (1.3%, n=2, p≤0.001).
Across both studies at 36 weeks – the study's primary endpoint –
1 out of 3 patients treated with OLUMIANT 4-mg
(BRAVE-AA1=35.2% [n=99]; BRAVE-AA2=32.5% [n=76]) and approximately
1 out of 5 patients treated with OLUMIANT 2-mg (BRAVE-AA1=21.7%
[n=40]; BRAVE-AA2=17.3% [n=27]) achieved 80% or more scalp hair
coverage, compared to 5.3% of patients taking placebo (n=10) and
2.6% (n=4) in BRAVE-AA1 and BRAVE-AA2, respectively (p≤0.001 for
all comparisons to placebo).
Achievement of full regrowth or regrowth with minimal gaps in
eyebrow and eyelash hair was also seen at 36 weeks with OLUMIANT
4-mg for 1 in 3 patients who at baseline had significant gaps or no
notable eyebrows, as compared to patients taking placebo (BRAVE-AA1
eyebrow=31.4% [n=59]; BRAVE-AA1 eyelash=33.5% [n=56]; BRAVE-AA1
eyebrow placebo=3.2% [n=4]; BRAVE-AA1 eyelash placebo=3.1% [n=3];
BRAVE-AA2 eyebrow=34.8% [n=56]; BRAVE-AA2 eyelash=34.3% [n=48];
BRAVE-AA2 eyebrow placebo=4.5% [n=5]; BRAVE-AA2 eyelash
placebo=5.6% [n=5]). This was measured by Clinician-Reported
Outcome (ClinRO) Measure for Eyebrow Hair Loss™ and ClinRO Measure
for Eyelash Hair Loss™ scores of patients achieving eyebrow and
eyelash hair loss scores of 0 or 1 (full coverage or minimal gaps)
with a ≥2-point improvement from baseline at 36 weeks,
respectively, compared to placebo (p≤0.001 for all comparisons to
placebo).
Statistically significant eyebrow regrowth results (19.1%, n=26,
p≤0.001) were also found for OLUMIANT 2-mg in BRAVE-AA1 at 36
weeks, but not in BRAVE-AA2. Eyelash results were not statistically
significant with OLUMIANT 2-mg in either study.
The safety profile of OLUMIANT was consistent with
previously-published safety data, and no new safety signals were
observed in the 36-week duration of these clinical trials. Few
patients discontinued treatment due to adverse events (2.6% or less
across both studies and doses), and the majority of
treatment-emergent adverse events were mild or moderate in
severity. The most commonly reported adverse events (≥5% in any
treatment group in BRAVE-AA1 or BRAVE-AA2) included: upper
respiratory tract infections, headache, acne, urinary tract
infection and increases in blood markers related to the muscle.
For methodology, see the "About the Studies" section below.
"These findings are promising for patients with severe alopecia
areata, as they support the potential for OLUMIANT to help patients
regrow hair on the scalp, eyebrows and eyelashes," said
Brett King, M.D., Ph.D., F.A.A.D.,
associate professor of dermatology at Yale
University School of Medicine and lead author of these
analyses. "Because there are no approved systemic therapies for
alopecia areata, there is significant unmet need and health care
providers and patients eagerly await approved treatment options for
this disease."
Tolerability of OLUMIANT Was Further Demonstrated for Acne,
Headache, and Gastrointestinal (GI) Events in Pooled Analysis
Across Eight Studies of 2,500 Patients with AD
In a pooled analysis across eight studies, tolerability outcomes
for acne, headache and GI adverse events (diarrhea, abdominal pain,
nausea, vomiting and constipation) were evaluated in more than
2,500 adult patients with moderate to severe atopic dermatitis (AD)
taking OLUMIANT 2-mg and 4-mg once daily.
Among those patients treated with OLUMIANT, 2.9% of patients
(n=74/2,531) had an adverse event of acne and 6.6% had an adverse
event of headache (n=166/2,531). The most common gastrointestinal
events were diarrhea (3.1% [n=78/2,531]) and nausea (1.9%
[n=49/2,531]). Most of these events were mild to moderate in
severity. The number of patients with adverse events that were
assessed as severe was low, with 10 patients (~0.4%) reporting
severe adverse events (4 due to headache, 2 due to diarrhea, 1 due
to abdominal pain, 1 due to upper abdominal pain, 1 due to nausea
and 1 due to vomiting). A total of 6 patients (~0.2%) had temporary
study interruptions (4 due to headache, 1 due to vomiting and 1 due
to abdominal pain), and 5 patients (~0.2%) permanently discontinued
(2 due to headache, 1 due to nausea and 2 due to abdominal pain)
for any of these events.
For methodology and additional results, see the "About the
Studies" section below.
"OLUMIANT has one of the largest and longest sets of available
safety data in the JAK inhibitor class, spanning approximately
19,000 patient years in a period of over nine years across the
clinical development program," said Lotus Mallbris, M.D., Ph.D.,
vice president of immunology development and U.S. and global
medical affairs at Lilly. "We are encouraged that these data
presented at EADV reinforce OLUMIANT's potential to be a
breakthrough treatment for people suffering from significant hair
loss due to alopecia areata."
About The Studies
- Efficacy and Safety of Baricitinib in Adults with Alopecia
Areata: Phase 3 Results from Two Randomized Controlled Trials
(BRAVE-AA1 and BRAVE-AA2)
-
- In BRAVE-AA1 and BRAVE-AA2, respectively, 654 and 546 patients
were randomized, and 598 (91.4%) and 490 (89.7%) completed 36 weeks
of treatment. In both BRAVE-AA1 and BRAVE-AA2, adults with severe
AA at screening and baseline (defined as Severity of Alopecia Tool
[SALT] score ≥50) were randomized 3:2:2 to once-daily OLUMIANT
4-mg, 2-mg or placebo.
- The primary endpoint was the proportion of patients achieving
SALT score ≤20 (≤20% scalp hair loss or ≥80% hair coverage) at 36
weeks. Key secondary outcomes included the proportions of patients
achieving ClinRO Measure for Eyebrow Hair Loss™ and ClinRO Measure
for Eyelash Hair Loss™ scores of 0 or 1 (full coverage or minimal
gaps) with ≥2-point improvements from baseline at Week 36 (among
those with baseline scores ≥2 [significant gaps to no notable
hair]).
- Data were censored after treatment discontinuation or if
collected remotely due to the COVID-19 pandemic. Treatment
comparisons were analyzed using logistic regression with
non-responder imputation applied to missing data.
- Pooled Analysis of Baricitinib Tolerability in Patients with
Atopic Dermatitis in Relation to Acne, Headache, and
Gastrointestinal Events From 8 Clinical Trials
-
- This pooled analysis included patient-level safety data from
eight clinical trials, including six double-blinded, randomized,
placebo-controlled studies, one double-blinded, randomized,
long-term extension study and one open-label, long-term extension
study. A total of 2,531 patients were given OLUMIANT for 2,247
patient-years.
- Outcomes are reported in three analysis sets:
placebo-controlled, 2-mg – 4-mg extended, and all-OLUMIANT AD.
Tolerability outcomes included the common treatment-emergent
adverse events of acne, headache, and GI events (diarrhea, nausea,
vomiting, constipation, and abdominal pain). The proportion of
patients with events and adjusted incidence rates were calculated
along with analysis of severity, onset and duration of events.
OLUMIANT is also being investigated for the treatment of adults
with systemic lupus erythematosus, juvenile idiopathic arthritis,
and COVID-19 (outside of Japan).
AA is the second potential treatment indication in dermatology for
OLUMIANT.
About OLUMIANT®
OLUMIANT, a once-daily,
oral JAK inhibitor was discovered by Incyte and licensed to Lilly.
It is approved in the U.S. and more than 75 countries as a
treatment for adults with moderate to severe rheumatoid arthritis
and is approved in more than 40 countries, including the European
Union and Japan, for the treatment of adult patients with
moderate to severe atopic dermatitis who are candidates for
systemic therapy. Marketing authorization for the treatment of
hospitalized patients with COVID-19 has been granted for OLUMIANT
in multiple countries including Japan and Switzerland. The U.S. FDA-approved labeling
for OLUMIANT includes a Boxed Warning for Serious Infections,
Malignancy, and Thrombosis. See the full Prescribing
Information here. Baricitinib is also being investigated
in alopecia areata (AA), juvenile idiopathic arthritis (JIA) and
systematic lupus erythematosus (SLE).
In December 2009, Lilly and Incyte announced an exclusive
worldwide license and collaboration agreement for the development
and commercialization of baricitinib and certain follow-on
compounds for patients with inflammatory and autoimmune
diseases.
Indication and Usage for OLUMIANT (baricitinib) tablets
(in the United States) for RA
patients
OLUMIANT® (baricitinib) 2 mg is
indicated for the treatment of adult patients with moderately to
severely active rheumatoid arthritis who have had an inadequate
response to one or more tumor necrosis factor (TNF) antagonist
therapies. Limitation of Use: Not recommended for use in
combination with other JAK inhibitors, biologic disease-modifying
antirheumatic drugs (DMARDs), or with potent immunosuppressants
such as azathioprine and cyclosporine.
IMPORTANT SAFETY INFORMATION FOR OLUMIANT (baricitinib)
tablets
WARNING: SERIOUS INFECTIONS, MALIGNANCY, AND
THROMBOSIS
SERIOUS INFECTIONS: Patients treated with Olumiant are at
risk for developing serious infections that may lead to
hospitalization or death. Most patients who developed these
infections were taking concomitant immunosuppressants such as
methotrexate or corticosteroids. If a serious infection develops,
interrupt Olumiant until the infection is controlled. Reported
infections include:
- Active tuberculosis (TB), which may present with pulmonary
or extrapulmonary disease. Test patients for latent TB before
initiating Olumiant and during therapy. If positive, start
treatment for latent infection prior to Olumiant use.
- Invasive fungal infections, including candidiasis and
pneumocystosis. Patients with invasive fungal infections may
present with disseminated, rather than localized, disease.
- Bacterial, viral, and other infections due to opportunistic
pathogens.
Carefully consider the risks and benefits of Olumiant prior
to initiating therapy in patients with chronic or recurrent
infection.
Closely monitor patients for the development of signs and
symptoms of infection during and after treatment with Olumiant
including the possible development of TB in patients who tested
negative for latent TB infection prior to initiating
therapy.
MALIGNANCIES: Lymphoma and other malignancies have been
observed in patients treated with Olumiant.
THROMBOSIS: Thrombosis, including deep venous thrombosis
(DVT) and pulmonary embolism (PE), has been observed at an
increased incidence in patients treated with Olumiant compared to
placebo. In addition, there were cases of arterial thrombosis. Many
of these adverse events were serious and some resulted in death.
Patients with symptoms of thrombosis should be promptly
evaluated.
WARNINGS AND PRECAUTIONS
SERIOUS INFECTIONS: The most common serious
infections reported with Olumiant included pneumonia, herpes
zoster, and urinary tract infection. Among opportunistic
infections, tuberculosis, multidermatomal herpes zoster, esophageal
candidiasis, pneumocystosis, acute histoplasmosis, cryptococcosis,
cytomegalovirus, and BK virus were reported with Olumiant. Some
patients have presented with disseminated rather than localized
disease, and were often taking concomitant immunosuppressants such
as methotrexate or corticosteroids. Avoid Olumiant in patients with
an active, serious infection, including localized infections.
Consider the risks and benefits of treatment prior to initiating
Olumiant in patients:
- with chronic or recurrent infection
- who have been exposed to TB
- with a history of a serious or an opportunistic infection
- who have resided or traveled in areas of endemic tuberculosis
or endemic mycoses; or
- with underlying conditions that may predispose them to
infection.
Closely monitor patients for infections during and after
Olumiant treatment. Interrupt Olumiant if a patient develops a
serious infection, an opportunistic infection, or sepsis. Do not
resume Olumiant until the infection is controlled.
Tuberculosis – Before initiating Olumiant,
evaluate and test patients for latent or active infection and treat
patients with latent TB with standard antimycobacterial therapy.
Olumiant should not be given to patients with active TB. Consider
anti-TB therapy prior to initiating Olumiant in patients with a
history of latent or active TB in whom an adequate course of
treatment cannot be confirmed, and for patients with a negative
test for latent TB but who have risk factors for TB infection.
Monitor patients for TB during Olumiant treatment.
Viral Reactivation – Viral reactivation,
including cases of herpes virus reactivation (e.g., herpes zoster),
were reported in clinical studies with Olumiant. If a patient
develops herpes zoster, interrupt Olumiant treatment until the
episode resolves.
The impact of Olumiant on chronic viral hepatitis reactivation
is unknown. Screen for viral hepatitis in accordance with clinical
guidelines before initiating Olumiant.
MALIGNANCY AND LYMPHOPROLIFERATIVE
DISORDERS: Malignancies were observed in Olumiant clinical
studies. Consider the risks and benefits of Olumiant prior to
initiating therapy in patients with a known malignancy other than a
successfully treated non-melanoma skin cancer (NMSC) or when
considering continuing Olumiant in patients who develop a
malignancy. NMSCs were reported in patients treated with Olumiant.
Periodic skin examination is recommended for patients who are at
increased risk for skin cancer.
THROMBOSIS: Thrombosis, including DVT and PE, has
been observed at an increased incidence in Olumiant-treated
patients compared to placebo. In addition, arterial thrombosis
events in the extremities have been reported in clinical studies
with Olumiant. Many of these adverse events were serious and some
resulted in death. There was no clear relationship between platelet
count elevations and thrombotic events. Use Olumiant with caution
in patients who may be at increased risk of thrombosis. If clinical
features of DVT/PE or arterial thrombosis occur, evaluate patients
promptly and treat appropriately.
GASTROINTESTINAL PERFORATIONS: Gastrointestinal
perforations have been reported in Olumiant clinical studies,
although the role of JAK inhibition in these events is not known.
Use Olumiant with caution in patients who may be at increased risk
for gastrointestinal perforation (e.g., patients with a history of
diverticulitis). Promptly evaluate patients who present with new
onset abdominal symptoms for early identification of
gastrointestinal perforation.
LABORATORY ABNORMALITIES:
Neutropenia – Olumiant treatment was associated
with an increased incidence of neutropenia (absolute neutrophil
count [ANC] <1000 cells/mm3) compared to placebo. Avoid
initiation or interrupt Olumiant treatment in patients with an ANC
<1000 cells/mm3. Evaluate at baseline and thereafter according
to routine patient management.
Lymphopenia – Absolute lymphocyte count (ALC)
<500 cells/mm3 were reported in Olumiant clinical trials.
Lymphocyte counts less than the lower limit of normal were
associated with infection in patients treated with Olumiant, but
not placebo. Avoid initiation or interrupt Olumiant treatment in
patients with an ALC <500 cells/mm3. Evaluate at baseline and
thereafter according to routine patient management.
Anemia – Decreases in hemoglobin levels to
<8 g/dL were reported in Olumiant clinical trials. Avoid
initiation or interrupt Olumiant treatment in patients with
hemoglobin <8 g/dL. Evaluate at baseline and thereafter
according to routine patient management.
Liver Enzyme Elevations – Olumiant treatment
was associated with increased incidence of liver enzyme elevation
compared to placebo. Increases of ALT ≥5x upper limit of normal
(ULN) and increases of AST ≥10x ULN were observed in patients in
Olumiant clinical trials.
Evaluate at baseline and thereafter according to routine patient
management. Promptly investigate the cause of liver enzyme
elevation to identify potential cases of drug-induced liver injury.
If increases in ALT or AST are observed and drug-induced liver
injury is suspected, interrupt Olumiant until this diagnosis is
excluded.
Lipid Elevations – Treatment with Olumiant was
associated with increases in lipid parameters, including total
cholesterol, low-density lipoprotein cholesterol, and high-density
lipoprotein cholesterol. Assess lipid parameters approximately 12
weeks following Olumiant initiation. Manage patients according to
clinical guidelines for the management of hyperlipidemia.
VACCINATIONS: Avoid use of live vaccines with
Olumiant. Update immunizations in agreement with current
immunization guidelines prior to initiating Olumiant therapy.
HYPERSENSITIVITY: Reactions such as angioedema,
urticaria, and rash that may reflect drug sensitivity have been
observed in patients receiving Olumiant, including serious
reactions. If a serious hypersensitivity reaction occurs, promptly
discontinue Olumiant while evaluating the potential causes of the
reaction.
ADVERSE REACTIONS
Most common adverse reactions include: upper respiratory tract
infections (16.3%, 11.7%), nausea (2.7%, 1.6%), herpes simplex
(0.8%, 0.7%), and herpes zoster (1.0%, 0.4%) for Olumiant 2 mg and
placebo, respectively.
USE IN SPECIFIC POPULATIONS
PREGNANCY AND LACTATION: No information is available
to support the use of Olumiant in pregnancy or lactation. Advise
women not to breastfeed during treatment with Olumiant.
HEPATIC AND RENAL IMPAIRMENT: Olumiant is not
recommended in patients with severe hepatic impairment or in
patients with severe renal impairment.
Please click to access full Prescribing
Information, including Boxed Warning about Serious infections,
Malignancies, and Thrombosis, and Medication Guide.
BA HCP ISI 09JUL2020
About Alopecia Areata
Alopecia areata (AA) is an
autoimmune disease that causes patchy hair loss on the scalp, face
and sometimes on other areas of the body that can progress. AA
often first appears during childhood and can be different for
everyone who has it. People of all ages, males/females and all
ethnic groups can develop AA.
About Atopic Dermatitis
Atopic dermatitis (AD), or
atopic eczema, is a chronic, relapsing skin disease characterized
by intense itching, dry skin and inflammation that can be present
on any part of the body. AD is a heterogeneous disease both
biologically and clinically, and may be characterized by a highly
variable appearance in which flares occur in an unpredictable
manner.
Moderate-to-severe AD is characterized by intense itching, which
leads to an itch-scratch cycle that further damages the skin. Like
other chronic inflammatory diseases, AD is immune-mediated and
involves a complex interplay of immune cells and inflammatory
cytokines.
About Eli Lilly and Company
Lilly is a global health
care leader that unites caring with discovery to create medicines
that make life better for people around the world. We were founded
more than a century ago by a man committed to creating high-quality
medicines that meet real needs, and today we remain true to that
mission in all our work. Across the globe, Lilly employees work to
discover and bring life-changing medicines to those who need them,
improve the understanding and management of disease, and give back
to communities through philanthropy and volunteerism. To learn more
about Lilly, please visit us at lilly.com and
lilly.com/newsroom.
About Incyte
Incyte is a Wilmington, Delaware-based, global
biopharmaceutical company focused on finding solutions for serious
unmet medical needs through the discovery, development and
commercialization of proprietary therapeutics. For additional
information on Incyte, please visit Incyte.com and follow
@Incyte.
OLUMIANT® is a registered trademark owned or licensed
by Eli Lilly and Company, its subsidiaries, or affiliates.
P-LLY
Lilly Forward-Looking Statement
This press release contains forward-looking statements (as that
term is defined in the Private Securities Litigation Reform Act of
1995) about OLUMIANT (baricitinib) as a potential treatment for
patients with alopecia areata and for other conditions and reflects
Lilly's and Incyte's current beliefs and expectations. However, as
with any pharmaceutical product, there are substantial risks and
uncertainties in the process of drug research, development, and
commercialization. Among other things, there can be no guarantee
that planned or ongoing studies will be completed as planned, that
future study results will be consistent with the results to date,
and that OLUMIANT will receive additional regulatory approvals, or
be commercially successful. For further discussion of these and
other risks and uncertainties, see Lilly's and Incyte's most recent
respective Form 10-K and Form 10-Q filings with the United States
Securities and Exchange Commission. Except as required by law,
Lilly and Incyte undertake no duty to update forward-looking
statements to reflect events after the date of this release.
Refer
to:
|
Marlo Scott;
scott_marlo@lilly.com; +1-317-407-8879 (Lilly
media)
|
|
Kevin Hern;
hern_kevin_r@lilly.com; +1-317-277-1838 (Lilly
investors)
|
|
Catalina Loveman;
cloveman@incyte.com; +1-302-498-6171 (Incyte media)
|
|
Christine Chiou;
cchiou@incyte.com; +1-302-274-4773 (Incyte investors)
|
View original content to download
multimedia:https://www.prnewswire.com/news-releases/olumiant-significantly-improved-hair-regrowth-to-at-least-80-scalp-coverage-as-early-as-24-weeks-across-first-completed-phase-3-studies-for-alopecia-areata-301388398.html
SOURCE Eli Lilly and Company