Date: 2014-04-30
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 2014 American Society of Cataract and Refractive Surgery (ASCRS) annual meeting in Boston
Company: Shire (UK-USA)
Product: lifitegrast
Action
mechanism: Lifitegrast, a small-molecule integrin antagonist, was designed in order to treat dry eye disease, and is a preservative-free topical eye solution. Lifitegrast is believed to work by reducing inflammation through inhibition of lymphocyte function-associated antigen 1 (LFA-1) and preventing its binding to intercellular adhesion molecule-1 (ICAM-1) that influences T-cell activation and cytokine (protein) release. The interaction between these two proteins plays a key role in the chronic inflammation associated with dry eye. T-cells are important components of the immune system that help control the body\'s response to a foreign or harmful substance or stimuli.
Disease: dry eye disease
Therapeutic area: Ophtalmological diseases
Country: USA
Trial
details:
The phase 3 clinical development program for lifitegrast includes three trials, OPUS-1, OPUS-2 and SONATA.
OPUS-1 was a multicenter, placebo-controlled trial conducted in a controlled adverse environment with 588 dry eye subjects to investigate the efficacy and safety of lifitegrast (5.0% solution) versus placebo twice daily for 84 days. In OPUS-1, the pre-specified co-primary endpoints were: 1) mean change from baseline to Day 84 in the inferior corneal fluorescein staining score (i.e., “sign”); and 2) the mean change from baseline to Day 84 in the Visual Related (VR) function subscale of the Ocular Surface Disease Index (OSDI) (i.e., “symptom”). In this study, lifitegrast demonstrated superiority over placebo on the sign endpoint of improvement of the inferior corneal fluorescein staining score (P=0.0007). Ocular surface damage, which is a hallmark of chronic inflammation from dry eye disease, is often detected using this staining parameter. However, the co-primary symptom endpoint, the VR function subscale of the OSDI, did not achieve statistical significance.
There were no serious ocular adverse events. The most commonly reported ocular adverse events were irritation and pain upon initial instillation, and were generally mild in severity. (NCT01421498)
OPUS-2, initiated in December 2012, was conducted in the natural environment and compared lifitegrast to placebo administered twice daily for 84 days (12 weeks) in dry eye patients with history of active artificial tear use within 30 days prior to screening. Overall, 718 patients were randomized at 31 US sites. The study consisted of 5 visits over 98 days: screening visits Day -14 (Visit 1) to Day 0 (Visit 2), and treatment visits at Day 0 (Visit 2), Day 14 (Visit 3), Day 42 (Visit 4), and Day 84 (Visit 5).(NCT01743729)
SONATA, which was initiated in December 2012, is a prospective, randomized, double-masked, placebo-controlled trial in 300 dry eye subjects to evaluate the safety of lifitegrast for 1 year. This trial is scheduled for completion in mid 2014. SONATA was a Phase 3, multicenter, randomized, double–masked, placebo–controlled study evaluating the safety of 5.0% lifitegrast compared to placebo administered twice-daily for 360 days (~ one year) in dry eye patients. In addition to certain medications, key study exclusions included any ocular condition that, in the opinion of the investigator, could affect study parameters. Patients had to have a visual analogue scale score greater than or equal to 40% in either symptom of eye dryness or discomfort, a corneal staining score of greater than or equal to 2.0 point in at least one region in either eye, and a Schirmer Tear Test score of greater than or equal to 1 and less than or equal to 10 mm in either eye at Visit 1 (Day -7). Confirmatory screening and baseline assessment occurred at Visit 2 (Day 0). Patients randomized into the study were not allowed to use contact lenses, or any topical ophthalmic treatments including artificial tears, steroid drops, antihistamine drops or mast cell stabilizer drops between Visits 1 and 3 (Day 14). Following completion of Visit 3 assessments, subjects were allowed elective use of contact lenses (daily disposable lenses only), and/or artificial tears (up to four times a day as needed) and/or topical ophthalmic steroids (loteprednol only), antihistamines or mast cell stabilizers. Overall, 332 patients were randomized (2:1, 5.0% lifitegrast: placebo) at 22 U.S. sites. The study consisted of seven visits over 367 days: screening visits Day -7 (Visit 1) to Day 0 (Visit 2), and treatment visits at Day 0 (Visit 2), Day 14 (Visit 3), Day 90 (Visit 4), Day 180 (Visit 5), Day 270 (Visit 6), and Day 360 (Visit 7).(NCT01636206)
Latest
news: * On April 30, 2014, Shire has presented study results from its pivotal Phase 3 OPUS -2 study investigating lifitegrast (5.0% ophthalmic solution) in adults with dry eye disease at the 2014 American Society of Cataract and Refractive Surgery (ASCRS) annual meeting in Boston. In addition, the company has announced top-line results from the prospective, randomized, double-masked, placebo-controlled, long-term (one-year) Phase 3 SONATA safety study. Lifitegrast is Sarcode Bioscience lead product. Shire has purchased this company in March 2013.
OPUS-2 study results on both co-primary endpoints and secondary assessments were presented at ASCRS. Lifitegrast met one of the co-primary endpoints for the patient-reported symptom of improvement in dry eye compared with placebo (P<0.0001), but did not meet the second co-primary endpoint of the sign of inferior corneal staining (P=0.6186). The secondary endpoints were only descriptive in nature and were consistent with improvement in symptoms and lack of improvement in signs. There were no ocular serious treatment-emergent adverse events (TEAEs) or drug-related serious TEAEs reported. The most commonly reported TEAEs associated with lifitegrast were dysgeusia (altered sense of taste) (16.2% vs. 0.3% for placebo), instillation site irritation (7.8% vs. 1.4% for placebo), instillation site reaction (7.0% vs. 1.1% for placebo), and visual acuity reduced (5.0% vs. 6.4% for placebo).
Top-line results from the prospective, randomized, double-masked, placebo-controlled SONATA trial indicated no ocular or drug-related serious adverse events. Discontinuations over the course of the study were 21.1% (23.1% for lifitegrast vs. 17.1% for placebo). At Day 360, analysis of the primary endpoints of ocular and non-ocular adverse events (AEs) showed that ocular AEs occurring in ≥5% of subjects included installation site irritation (15% vs. 4.5% for placebo), installation site reaction (13.2% vs. 1.8% for placebo), visual acuity reduced (11.4% vs. 6.3% for placebo), and dry eye (1.8% vs. 5.4% for placebo). The most commonly reported non-ocular AE associated with lifitegrast was dysgeusia (altered sense of taste) (16.4% vs. 1.8% for placebo). Additional data and analyses will be submitted for presentation at upcoming medical meetings.
* On December 5, 2013, Shire has announced top-line results from OPUS-2, a Phase 3 efficacy and safety study of 5.0% lifitegrast ophthalmic solution. OPUS-2 compared lifitegrast to placebo administered twice daily for 84 days (12 weeks) in dry eye patients with history of active artificial tear use within 30 days prior to screening. Lifitegrast met the prespecified co-primary endpoint for the patient-reported symptom of eye dryness (change in Eye Dryness Score from baseline to week 12) (p-value<0.0001). Lifitegrast did not meet the prespecified co-primary endpoint for the sign of inferior corneal staining score (change from baseline to Week 12) using fluorescein staining compared with placebo (p value=0.6186). The study also evaluated the safety and tolerability of lifitegrast based on occurrence of treatment-emergent adverse events (TEAEs). The most commonly reported TEAEs associated with lifitegrast were dysgeusia (altered sense of taste) (16.2% vs 0.3% for placebo), instillation site irritation (7.8% vs 1.4% for placebo), instillation site reaction (7.0% vs 1.1% for placebo) and visual acuity reduced (5.0% vs 6.4% for placebo). There were no ocular serious TEAEs or drug-related serious TEAEs. 93.2% of patients enrolled in the study remained for the entire duration of the 12-week clinical trial. “In this clinical trial, we note that lifitegrast showed a statistically significant improvement in the prespecified symptoms of dry eye disease and is the first drug to do so in a phase 3 clinical trial,” said Flemming Ornskov, M.D., Chief Executive Officer, Shire. “We will be examining the totality of the data for lifitegrast in OPUS-2, as well as OPUS-1 and across the entire clinical trial program. We look forward to discussing the lifitegrast program with regulatory authorities.”
