-- Phase 3 trial achieved its primary endpoint
and all secondary endpoints with marked improvement in key
indicators of disease --
Horizon Therapeutics plc (Nasdaq: HZNP) today announced that The
New England Journal of Medicine has published comprehensive results
of the Phase 3 OPTIC clinical trial evaluating TEPEZZA™
(teprotumumab-trbw) for Thyroid Eye Disease (TED). OPTIC is part of
the largest clinical program in TED and demonstrates that TEPEZZA
provides significant improvements in proptosis (eye bulging) and
diplopia (double vision) compared to placebo.
TEPEZZA is a fully human monoclonal antibody (mAb) and a
targeted inhibitor of the insulin-like growth factor-1 receptor
(IGF-1R) that is administered to patients once every three weeks
for a total of eight infusions. TEPEZZA was approved by the U.S.
Food and Drug Administration (FDA) on January 21, 2020 – making it
the first and only medicine approved for the treatment of TED. The
medicine received Priority Review, Orphan Drug, Fast Track and
Breakthrough Therapy designations from the FDA.
“Thyroid Eye Disease is a rare, devastating autoimmune disease
that is not adequately treated, leaving patients to struggle for
years until they become candidates for surgeries that are not only
complex, but often don’t fully restore vision or appearance,” said
Raymond Douglas, M.D., Ph.D., director of the Orbital and Thyroid
Eye Disease Program, Cedars-Sinai Medical Center and co-principal
investigator of the OPTIC trial. “In this clinical trial, we saw
statistically significant improvements across critical symptoms –
including proptosis and diplopia – at the first patient assessment
at six weeks of treatment, and those improvements continued over
the 24-week treatment period. TEPEZZA, which was just recently
approved by the FDA, has the potential to significantly change the
treatment paradigm in a disease where patients have historically
had to watch and wait in pain as symptoms progress and put them at
risk for serious vision impairment.”
OPTIC compared the efficacy and safety of TEPEZZA to placebo
administered by infusion once every three weeks for a total of
eight infusions. As previously reported, the trial met its primary
endpoint and all secondary endpoints.
Key trial findings published in The New England Journal of
Medicine include the following1:
- Proptosis: At Week 24, more
patients receiving TEPEZZA (83%) versus placebo (10%) had a ≥ 2 mm
reduction of proptosis in the study eye, without deterioration in
the fellow eye (p<0.001). Mean change in proptosis with TEPEZZA
was ─3.32 mm at Week 24, which is similar to the results attained
on average with orbital decompression surgery. All patients who
received TEPEZZA had some reduction in proptosis at Week 24,
regardless of the initial severity of proptosis, which ranged from
16 mm to 31 mm in the trial. The number needed-to-treat (NNT) was
1.36 (NNT is the number of patients needed to treat in order to
achieve response in one additional patient).
- Muscle and Fat Volume: Orbital
imaging was performed at one trial site, as a part of the site’s
standard practice, and showed that the reduction in proptosis was
associated with a reduction in extraocular muscle volume, orbital
fat volume or both. All six patients in the TEPEZZA group had
significantly decreased extraocular muscle volume in the study eye,
with an average percentage decrease of 35%. Orbital fat volume in
the study eye had an average percentage decrease of 17%. Orbital
fat volume was reduced by 44% in one patient and by 40% in
another.
- Diplopia: At Week 24, 68% of
patients receiving TEPEZZA had an improvement from baseline of at
least one grade in diplopia, compared to 29% of patients receiving
placebo (p=0.001). This endpoint measured the percentage of
patients who reported at least some diplopia at baseline in the
study eye and who had a reduction of ≥ 1 grade with no
corresponding deterioration (≥ 1 grade worsening) in the fellow eye
at Week 24.
- Quality of Life (QoL): At Week 24,
patients receiving TEPEZZA had a mean change of 17 on the Graves'
Ophthalmopathy Quality of Life (GO-QoL) scale compared with a
change of 2 for patients receiving placebo (p<0.001). These
scores indicate a statistically and clinically meaningful
improvement over placebo in these QoL measures. The GO-QoL scale
consists of two subscales to evaluate the quality of life of TED
(Graves’ Ophthalmology) patients, including impact on visual
function and self-assessment of appearance. A change of 6 points is
considered clinically significant.2
- Clinical Activity Score (CAS): At
Week 24, more patients achieved a CAS value of 0 or 1 with TEPEZZA
treatment (59% vs 21% of placebo participants) (p<0.001). CAS is
a scale used to assess the disease activity of TED, and measures
the degree of inflammation, including pain, swelling and redness.
The CAS scale ranges from 0 to 7, with a score of 0 representing no
swelling or activity.3
- Overall Responder Rate: At Week
24, patients treated with TEPEZZA had an overall responder rate of
78% compared with 7% in the placebo group (p<0.001). Overall
responder rate is the percent of participants with a ≥ 2-point
reduction in CAS and a ≥ 2 mm reduction in proptosis from baseline,
without deterioration in the fellow eye.
- In general, the onset of activity of TEPEZZA was rapid and
evident at the first post-baseline assessment at Week 6, with
continued improvement over the full 24-week course of
treatment.
“TEPEZZA is a biologic specifically designed to inhibit the
mechanism of Thyroid Eye Disease – actively reducing tissue
expansion and remodeling behind the eye,” said Elizabeth H.Z.
Thompson, Ph.D., vice president, clinical development, rare
disease, Horizon. “This is important because other therapies used
to treat Thyroid Eye Disease have not been shown to improve eye
bulging or double vision, which are two of the most common and
vision-threatening aspects of the disease. The OPTIC study
represents a meaningful step in our evolution to an
innovation-focused biopharma company, and its results suggest that
TEPEZZA has the potential to change the way the disease is
managed.”
The majority of adverse events experienced with TEPEZZA
treatment were graded as mild to moderate and were managed in the
trial, with few discontinuations. Adverse events (> 10%)
included muscle spasm, alopecia, nausea and fatigue. Adverse events
of special interest that occurred in 5% of patients or less within
21 days after the last dose included two patients in the TEPEZZA
group who experienced hyperglycemia (both cases were mild) and five
patients in the TEPEZZA group who experienced hearing impairment
(all cases resolved). No deaths occurred. Two serious adverse
events occurred in the TEPEZZA group: pneumothorax (probably
unrelated to the study drug, as determined by an investigator) and
an infusion reaction that led to withdrawal from the trial.
About Thyroid Eye Disease
Thyroid Eye Disease (TED) is a serious, progressive and
vision-threatening rare autoimmune disease.4 While TED often occurs
in people living with hyperthyroidism or Graves’ disease, it is a
distinct disease that is caused by autoantibodies activating an
IGF-1R-mediated signaling complex on cells within the retro-orbital
space.5,6 This leads to a cascade of negative effects, which may
cause long-term, irreversible damage. As TED progresses, it causes
serious damage – including proptosis (eye bulging), strabismus
(misalignment of the eyes) and diplopia (double vision) – and in
some cases can lead to blindness.7,8 Historically, patients have
had to live with TED until the inflammation subsides, after which
they are often left with permanent and vision-impairing
consequences.4,9
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, follow us @HorizonNews on
Twitter, like us on Facebook or explore career opportunities on
LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements,
including statements regarding the potential benefits of TEPEZZA as
a treatment of 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 whether TEPEZZA is successfully
commercialized and adopted by physicians and patients, 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
- Douglas, et al. Teprotumumab for the Treatment of Active
Thyroid Eye Disease. N Engl J Med. 2020;382(4):341-352.
- Terwee CB. Interpretation and Validity of Changes in Scores on
the Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL)
After Different Treatments. Clinical Endocrinology.
2001;54:391-398.
- Wiersinga WM, Perros P, Kahaly GJ, et al. Clinical Assessment
of Patients with Graves’ Orbitopathy: the European Group on Graves’
Orbitopathy Recommendations to Generalists, Specialists and
Clinical Researchers. Eur J Endocrinol. 2006;155:387-9.
- Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus
EUGOGO Classification, Assessment, and Management. Journal of
Ophthalmopathy. 2015;2015:1-16.
- 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.
- Bothun ED, et al. Update on thyroid eye disease and management.
Clinical Ophthalmology. 2009;3:543-551.
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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 Contact: Matt Flesch Vice President,
Communications and Patient Advocacy media@horizontherapeutics.com
Rachel Vann Associate Director, Product Communications
media@horizontherapeutics.com Ireland Media Contact:
Gordon MRM Ray Gordon ray@gordonmrm.ie
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