-- Presentation during American Academy of
Ophthalmology Annual Meeting (AAO 2020 Virtual) demonstrates
clinical improvement in the less severe eye --
-- Additional data from OPTIC 48-week follow-up
study and OPTIC-X extension trial, including findings showing that
the majority of TEPEZZA patients who were diplopia (double vision)
responders in OPTIC at week 24 maintained their response at week
72, nearly a year off-treatment --
-- Patients who received placebo during the
OPTIC Phase 3 clinical trial and then received TEPEZZA in the
OPTIC-X extension trial also achieved clinically significant
diplopia improvement with an average of 12 months of disease,
compared with six months in OPTIC --
Horizon Therapeutics plc (Nasdaq: HZNP) today announced new
TEPEZZA® (teprotumumab-trbw) data presented at the American Academy
of Ophthalmology Annual Meeting (AAO 2020 Virtual), including
findings suggesting benefits of TEPEZZA in the less severe eye of
patients with Thyroid Eye Disease (TED), and new data from the
OPTIC 48-week follow-up study and OPTIC-X clinical trial. TEPEZZA
is the first and only medicine approved by the U.S. Food and Drug
Administration (FDA) for the treatment of TED – a serious,
progressive and vision-threatening rare autoimmune disease.1
“We continue to analyze our existing clinical trials and pursue
new research to fully understand the impact TEPEZZA has on this
challenging disease,” said Elizabeth H.Z. Thompson, Ph.D., group
vice president, development and external search, Horizon. “Our data
demonstrating the effect of TEPEZZA at varying stages of the
disease, including in the less severely affected eye and in
patients who have had Thyroid Eye Disease for a longer period of
time, will help advance the science of Thyroid Eye Disease and
instill greater understanding of the role TEPEZZA can play in
improving patient outcomes.”
Compelling Response in Less Severe TED
Improvement in Fellow Eye of Patients with TED: Pooled Analyses
from Teprotumumab Studies (PO305)
In patients with TED, one eye can have more severe symptoms than
the other. The TEPEZZA Phase 2 clinical trial and OPTIC Phase 3
confirmatory clinical trial designated the more severely affected
eye as the “study eye”.2,3 This new analysis focused specifically
on efficacy of TEPEZZA in treating the less severe eye, or “fellow
eye”, of patients in the TEPEZZA Phase 2 and 3 trials. Researchers
analyzed the intent-to-treat (ITT) population in the Phase 2 and
Phase 3 studies, defined as all patients randomized to receive
TEPEZZA (n=84) and all patients randomized to receive placebo
(n=87). The fellow eye was less proptotic than the study eye in
both the TEPEZZA (21.61 mm vs. 23.02 mm) and placebo (21.97 mm vs.
23.15 mm) groups, indicating less severe disease. Additionally, the
fellow eye, on average, demonstrated less inflammation based on the
clinical activity score (CAS) than the study eye in both the
TEPEZZA (CAS: 4.3 vs. 5.1 points) and placebo (CAS: 4.7 vs. 5.3
points) groups.
Findings suggest that TEPEZZA may offer benefits in patients
with less severe TED:
- At Week 24, more TEPEZZA patients were proptosis (eye bulging)
responders (≥2 mm reduction) in the fellow eye than placebo
patients (63.1 percent vs. 8.0 percent, p<0.001), with a mean
reduction in proptosis of 2.39 mm for TEPEZZA patients and a mean
increase in proptosis of 0.15 mm for placebo patients
(p<0.001).
- 30 patients (34.5 percent) in the placebo group had a worsening
of proptosis at Week 24 in the fellow eye compared to 0 patients (0
percent) in the TEPEZZA group.
- CAS in the fellow eye decreased from baseline by a mean of
-3.42 points in the TEPEZZA group compared to -2.00 points in the
placebo group (p<0.001) at Week 24.
- More TEPEZZA patients (63.1 percent) than placebo patients
(26.4 percent) had a CAS of 0 or 1 – signifying disease
inactivation – in the fellow eye at Week 24 (p<0.001).
“We know from the clinical development program that TEPEZZA
significantly reduces proptosis and Thyroid Eye Disease-related
inflammation in patients with moderate-to-severe disease, and now
with this new analysis of the Phase 2 and 3 data, we have evidence
pointing to efficacy in patients with less severe disease as well,”
said Raymond Douglas, M.D., Ph.D., study author and director of the
Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical
Center. “We believe this robust effect is the result of the
mechanism of TEPEZZA that effectively targets the underlying
molecular pathways that cause Thyroid Eye Disease.”
Additional Findings from the OPTIC 48-Week Follow-Up Study
and OPTIC-X Clinical Trial
Long Term Assessment of Proptosis and Diplopia from the OPTIC
Trial of Teprotumumab in Thyroid Eye Disease (PA038)
Additional data from the OPTIC Phase 3 confirmatory clinical
trial and the OPTIC-X open-label extension clinical trial were also
included in an abstract and presented during AAO, supplementing the
topline results on proptosis response announced in July 2020. The
OPTIC trial included a 24-week treatment period (treatment every
three weeks for a total of eight infusions) and a 48-week
off-treatment follow-up period. OPTIC-X evaluated TEPEZZA in
patients who were enrolled in OPTIC and were either proptosis
non-responders at Week 24 or were proptosis responders at Week 24
but flared during the 48-week off-treatment follow-up period.
New OPTIC 48-week off-treatment follow-up study findings include
the following:
- The majority of TEPEZZA patients who had at least 1 grade of
diplopia (double vision) improvement at Week 24 in OPTIC maintained
their response at Week 72 (11/19; 58 percent) without receiving
additional TED treatment.
- 50 percent of TEPEZZA patients (8/16) who had a diplopia score
of 0 at Week 24 in OPTIC maintained a diplopia score of 0 at Week
72 without receiving additional TED treatment.
New OPTIC-X findings include the following:
- 61 percent of patients (14/23) who received placebo during the
OPTIC trial and then entered OPTIC-X and received TEPEZZA were
considered diplopia responders (≥1 grade improvement) at Week 24.
This is consistent with results from the OPTIC trial, where 68
percent of patients (19/28) who received TEPEZZA had a change from
baseline of at least 1 grade in diplopia at Week 24. OPTIC-X
patients had an average of 12 months of TED compared with six
months in OPTIC.
- Five patients who received placebo during the OPTIC trial and
then entered OPTIC-X had a CAS of 0 or 1, which means they had
minimal or no inflammation. Of those, 60 percent (3/5) were
proptosis responders at Week 24 (≥2 mm improvement in proptosis
from baseline in the study eye without deterioration in the fellow
eye at Week 24).
There were no new safety concerns in OPTIC-X or the OPTIC
48-week off-treatment follow-up period, including in patients who
received additional TEPEZZA treatment.
About Thyroid Eye Disease (TED)
TED is a serious, progressive and vision-threatening rare
autoimmune disease.1 TED often occurs in people living with
hyperthyroidism or Graves’ disease; however, it is a distinct
disease that is caused by autoantibodies activating an
IGF-1R-mediated signaling complex on cells within the retro-orbital
space.4,5 This leads to a cascade of negative effects, which may
cause long-term, irreversible damage. As TED progresses, the
serious damage it can cause includes proptosis (eye bulging),
strabismus (misalignment of the eyes) and diplopia (double vision)
– and in some cases can lead to blindness.6,7
About TEPEZZA
INDICATION
TEPEZZA is indicated for the treatment of Thyroid Eye
Disease.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Infusion Reactions: TEPEZZA may cause infusion reactions.
Infusion reactions have been reported in approximately 4% of
patients treated with TEPEZZA. Reported infusion reactions have
usually been mild or moderate in severity. Signs and symptoms may
include transient increases in blood pressure, feeling hot,
tachycardia, dyspnea, headache and muscular pain. Infusion
reactions may occur during an infusion or within 1.5 hours after an
infusion. In patients who experience an infusion reaction,
consideration should be given to premedicating with an
antihistamine, antipyretic, or corticosteroid and/or administering
all subsequent infusions at a slower infusion rate.
Preexisting Inflammatory Bowel Disease: TEPEZZA may cause
an exacerbation of preexisting inflammatory bowel disease (IBD).
Monitor patients with IBD for flare of disease. If IBD exacerbation
is suspected, consider discontinuation of TEPEZZA.
Hyperglycemia: Increased blood glucose or hyperglycemia
may occur in patients treated with TEPEZZA. In clinical trials, 10%
of patients (two-thirds of whom had preexisting diabetes or
impaired glucose tolerance) experienced hyperglycemia.
Hyperglycemic events should be managed with medications for
glycemic control, if necessary. Monitor patients for elevated blood
glucose and symptoms of hyperglycemia while on treatment with
TEPEZZA. Patients with preexisting diabetes should be under
appropriate glycemic control before receiving TEPEZZA.
Adverse Reactions
The most common adverse reactions (incidence ≥5% and greater
than placebo) are muscle spasm, nausea, alopecia, diarrhea,
fatigue, hyperglycemia, hearing impairment, dysgeusia, headache and
dry skin.
For additional information on TEPEZZA, please see Full
Prescribing Information at TEPEZZAhcp.com.
About Horizon
Horizon is focused on researching, developing and
commercializing medicines that address critical needs for people
impacted by rare and rheumatic diseases. Our pipeline is
purposeful: we apply scientific expertise and courage to bring
clinically meaningful therapies to patients. We believe science and
compassion must work together to transform lives. For more
information on how we go to incredible lengths to impact lives,
please visit www.horizontherapeutics.com and follow us on Twitter,
LinkedIn, Instagram and Facebook.
Forward-Looking Statements
This press release contains forward-looking statements,
including statements regarding the potential benefits of TEPEZZA as
a treatment of less severe TED. These forward-looking statements
are based on management expectations and assumptions as of the date
of this press release, and actual results may differ materially
from those in these forward-looking statements as a result of
various factors. These factors include risks associated with future
clinical development, whether TEPEZZA will be adopted as a
treatment for less severe TED, as well as those described in
Horizon's filings with the United States Securities and Exchange
Commission, including those factors discussed under the caption
“Risk Factors” in those filings. Forward-looking statements speak
only as of the date of this press release and Horizon does not
undertake any obligation to update or revise these statements,
except as may be required by law.
References
- Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus
EUGOGO Classification, Assessment, and Management. Journal of
Ophthalmopathy. 2015;2015:1-16.
- Smith, et al. Teprotumumab for Thyroid-Associated
Ophthalmology. N Engl J Med. 2017;376:1748-1761.
- Douglas, et al. Teprotumumab for the Treatment of Active
Thyroid Eye Disease. N Engl J Med. 2020;382(4):341-352.
- Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in
Thyroid Associated Ophthalmopathy. Autoimmunity.
1993;16(4):251–257.
- Pritchard J, et al. Immunoglobulin Activation of T Cell
Chemoattractant Expression in Fibroblasts from Patients with
Graves’ Disease Is Mediated Through the Insulin-Like Growth Factor
1 Receptor Pathway. J Immunol. 2003;170:6348-6354.
- Ross DS, et al. The 2016 European Thyroid Association/European
Group on Graves' Orbitopathy Guidelines for the Management of
Graves' Orbitopathy. Eur Thyroid J. 2016;5(1):9-26.
- McKeag D, et al. Clinical features of dysthyroid optic
neuropathy: a European Group on Graves' Orbitopathy (EUGOGO )
survey. Br J Ophthalmol. 2007;91:455-458.
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Tina Ventura Senior Vice President, Investor Relations
Investor-relations@horizontherapeutics.com
Ruth Venning Executive Director, Investor Relations
Investor-relations@horizontherapeutics.com
U.S. Media Contacts: Rachel Vann Director, Product
Communications media@horizontherapeutics.com
Ireland Media Contact: Gordon MRM Ray Gordon
ray@gordonmrm.ie
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