Horizon Pharma Submits New Drug Application for LODOTRA(R) for the Treatment of Rheumatoid Arthritis
Horizon Pharma Submits New Drug Application for LODOTRA(R) for the Treatment of Rheumatoid Arthritis
"The NDA submission for LODOTRA represents an important milestone for our continued growth in
The LODOTRA NDA submission was primarily based on results from the Circadian Administration of Prednisone in RA (CAPRA-2) trial, a pivotal, 12-week, double-blind, placebo-controlled Phase 3 trial involving 350 RA patients. Both treatment groups in the trial continued to receive standard of care RA treatment with a disease-modifying anti-rheumatic drug (DMARD). Results from CAPRA-2 demonstrated:
- A statistically significant improvement in
American College of Rheumatology 20 (ACR20) response criteria, the primary study endpoint, for patients who were treated with LODOTRA compared to the placebo group (48.5% vs. 28.6%; p-value = 0.0002). - A statistically significant improvement in ACR50 response compared to placebo (22.7% vs. 9.2%; p-value = 0.0027) and an improvement in the more stringent ACR70 response criteria (7.0% vs. 2.5%; p-value = 0.0955).
- A statistically significant reduction in morning stiffness compared to patients in the placebo group (56.5% vs. 33.3%; p-value = 0.0008).
In this study, the most commonly reported treatment-emergent adverse events were joint pain (10.4% for LODOTRA compared to 20.2% for placebo), RA flare (6.5% for LODOTRA compared to 9.2% for placebo), nasopharyngitis, or inflammation of the nasal passages, (4.8% for LODOTRA compared to 3.4% for placebo) and headache (3.9% for LODOTRA compared to 4.2% for placebo).
Additional data in the NDA submission included results from the CAPRA-1 study, which was a 12 week, double-blind, placebo-controlled study in
- A statistically significant reduction in morning stiffness compared to patients in the immediate release group, the primary outcome of the trial, (22.7% for LODOTRA compared to 0.4% for immediate release prednisone (p-value = 0.045)).
- Patients treated with LODOTRA had a reduction in IL-6 levels of approximately 29% (relative median change), which was statistically significant, while corresponding IL-6 levels following treatment with immediate release prednisone remained constant.
The most commonly reported treatment-emergent adverse events were a flare in RA-related symptoms (7.6% for LODOTRA compared to 9.0% for immediate release prednisone), abdominal pain (3.5% for LODOTRA compared to 5.6% for immediate release prednisone), nasopharyngitis (2.8% for LODOTRA compared to 5.6% for immediate release prednisone), headache (4.2% for LODOTRA compared to 2.8% for immediate release prednisone) and flushing (2.8% for LODOTRA and 4.2% for immediate release prednisone).
Following the 12-week CAPRA-1 study, patients were followed in a nine-month, open-label extension study, which included 249 RA patients, 219 of whom completed the extension study. Results showed that patients who continued treatment with LODOTRA experienced a 55% reduction in the duration of morning stiffness. Further, patients newly assigned to LODOTRA exhibited a 45% reduction in the duration of morning stiffness over the nine-month course of this extension study. These patients also experienced a 50% median reduction in IL-6 levels that also corresponded to improvements in the duration of morning stiffness following daily administration of LODOTRA.
The most commonly reported treatment-emergent adverse events in the extension study were a flare in RA-related symptoms (14.5%), flushing (5.2%), upper respiratory tract infections (2.8%), back pain (2.8%) and weight increase (2.8%). Adverse events indicative of aggravated hypothalamic-pituitary adrenal, or HPA, axis suppression, typical of high dose prednisone administration, were not observed.
About LODOTRA
LODOTRA is a proprietary modified (delayed)-release formulation of low-dose prednisone. Prednisone, the active ingredient in LODOTRA, is currently
A Phase 3 clinical trial of LODOTRA for the treatment of polymyalgia rheumatica (PMR) is being planned. This indication is not included in the NDA.
About RA
RA is a chronic disease that causes pain, stiffness and swelling, primarily in the joints. RA affects approximately 1.8 million people in the U.S. and is not associated with factors such as aging.
RA occurs when the body's immune system malfunctions, attacking healthy tissue and causing inflammation, which leads to pain and swelling in the joints, and may eventually cause permanent joint damage and painful disability. The primary symptoms of RA include progressive immobility and pain, especially in the morning, with long-term sufferers experiencing continual joint destruction for the remainder of their lives.
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ContactsRobert J. De Vaere Email Contact MediaMolly Rabinovitz Invigorate 312-646-6294 Email Contact InvestorsKathy Galante Burns McClellan, Inc. 212-213-0006 Email Contact
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