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New Medicines

XiidraKeratoconjunctivitis sicca (or dry eye disease)

Information

Xiidra
New molecular entity
Novartis Ophthalmics
Novartis Ophthalmics

Development and Regulatory status

Filing withdrawn
Filing withdrawn
Launched
Jun 20EU filing withdrawn by company. At the time of withdrawal, there were unresolved issues that the company did not feel able to addresss in the available time frame. The CHMP was of the provisional opinion that it could not recommend authorisation because the data did not adequately show an effect in the patient population it was intended to be used in. Additionally, there were no data on the long term effects. Therefore, at the time of withdrawal, the Agency’s opinion was that, because effectiveness was not proven, the benefits of Xiidra did not outweigh its risks [22].
Jul 19Novartis announced completion of its acquisition of Xiidra (lifitegrast ophthalmic solution) from Takeda [21]
May 19Novartis announced that it has entered into an agreement with Takeda to acquire the assets associated with Xiidra® (lifitegrast ophthalmic solution) 5% worldwide [20].
Dec 18Application accepted by the EMA - listed as a new entry in CHMP New Medicines Applications Under Evaluation report for 7/1/19 [19].
Jun 18Shire withdraws Xiidra filing from EU decentralised procedure and aims to file through the centralised procedure Q4 2018 [18].
Aug 17Filed in EU for the treatment of signs and symptoms of dry eye disease [17].
Feb 17Shire announces intention to submit for licensing in EU [16].
Aug 16Launched in US [16].
Jul 16Approved in US; launch planned for Q3 2016 [15].
Feb 16FDA agree to make a decision by July 22 [14].
Jan 16Re-filed in the US using data from a third late-stage study showing a statistically significant reduction in patient-reported eye dryness vs. placebo after 12 weeks and meeting secondary goals of improving symptoms from baseline at weeks two and 6 [13].
Oct 15Shire plans to file OPUS-3 data as part of the resubmission of the NDA for lifitegrast in Q1 16 [12].
Oct 15FDA issues a complete response letter, requesting an additional clinical study. Shire has recently completed a PIII study (OPUS-3), that is expected to be the basis of its response to the CRL. The FDA also requested more information related to product quality, which Shire will address in the CRL response. Topline results of OPUS-3 are expected before year-end, and, and if positive, the company plans to submit these data as part of a resubmission to the FDA during Q1 2016 [11].
Apr 15FDA accepts lifitegrast for priority review reducing assessment time from the standard 12 months to just eight months [10].
Mar 15Shire submits a New Drug Application in the US seeking permission to market its experimental drug lifitegrast for dry eye disease in adults. If successful, lifitegrast could become the first treatment approved to treat both the signs and symptoms of the chronic inflammatory condition [9].
May 14Following a meeting with the US FDA, Shire anticipates submitting a New Drug Application for lifitegrast as a treatment for signs and symptoms of dry eye disease in adults in 1Q 2015 [8].
Mar 13Shire is to acquire SARCode and says that it will file lifitegrast (SAR 1118) for US approval in 2016 [5].

Category

First-in-class molecule that inhibits T-cell inflammation by blocking the binding of 2 key cellular surface proteins (LFA-1 and ICAM-1) that mediate the chronic inflammatory cascade
Dry eyes is a common condition affecting up to a third of those aged over 65 years. It is 50% more common in women than in men. [3]
Keratoconjunctivitis sicca (or dry eye disease)
Topical

Further information

Yes

Trial or other data

Jul 20NICE report the company have advised that they are no longer pursuing a Marketing Authorisation Application from the EMA for this indication at this time. Therefore, NICE has decided to suspend this appraisal from its current work programme [23].
Oct 15Shire announces OPUS-3 met the primary endpoint of significantly improving patient-reported symptoms of dry eye disease from baseline to day 84 (p=0.0007). Additionally, OPUS-3 met the secondary endpoints of symptom improvement from baseline to days 14 and 42 (p<0.0001 for both endpoints) [12].
May 14Top-line results from the one-year PIII SONATA safety study indicate no ocular or drug-related serious adverse events. Discontinuations over the course of the study were 23.1% for lifitegrast vs. 17.1% for placebo. 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%), visual acuity reduced (11.4% vs. 6.3%), and dry eye (1.8% vs. 5.4%). The most commonly reported non-ocular AE associated with lifitegrast was dysgeusia (16.4% vs. 1.8%) [7].
Dec 13In the PIII OPUS-2 study, lifitegrast met one of the prespecified co-primary endpoints vs placebo for the patient-reported symptom of eye dryness (change in Eye Dryness Score from baseline to week 12) (p<0.0001), but not the change in inferior corneal staining score (change from baseline to Week 12) using fluorescein staining (p=0.6186). The most commonly reported treatment-emergent adverse events associated with lifitegrast were dysgeusia (16.2% vs 0.3% for placebo), instillation site irritation (7.8% vs 1.4%), instillation site reaction (7.0% vs 1.1%) and visual acuity reduced (5.0% vs 6.4) [6].
Jan 13The initial pt has been enrolled in a second pivotal PIII clinical efficacy study (OPUS-2) of lifitegrast ophthalmic solution 5.0%. OPUS-2 is a prospective, double-masked, PIII RCT (n=700) that will evaluate the efficacy and safety of lifitegrast compared to placebo for the treatment of signs and symptoms of dry eye disease. Pts with dry eye disease who have used artificial tears in the past 30 days will receive lifitegrast or placebo dosed two times a day for 12 weeks. The co-primary endpoints are the mean change from baseline in inferior corneal staining score and the mean eye dryness score, both assessed at 12 weeks. Additional secondary endpoints include total corneal staining, nasal lissamine staining, and ocular/eye discomfort. The safety and tolerability of lifitegrast compared to placebo will also be evaluated [4].
Oct 12Topline results from the PIII OPUS-1 study reported. Lifitegrast demonstrated superiority over placebo in improving inferior and total corneal staining scores from baseline to week 12 (P=0.0007 and P=0.0148, respectively). Lifitegrast also significantly improved ocular discomfort and eye dryness vs placebo at week 12 (P=0.0273 and P=0.0291, respectively). The most commonly reported ocular AEs were irritation and pain at the start of treatment, and were generally mild and transient in nature. The company recently started a year-long safety study (SONATA) and will soon begin a second pivotal PIII confirmatory study (OPUS-2) [4].
Apr 12Enrolment of 588 patients in OPUS-1 was completed in the US in March 2012. The company anticipates completing the trial and providing topline data by mid 2012. [2]
Sep 11First pt enrolled in PIII OPUS-1 trial of SAR 1118 ophthalmic solution for dry eye disease. About 588 patients will be randomised to receive SAR 1118 5.0% ophthalmic solution or placebo twice daily over 12 weeks. The co-primary endpoints of the study are corneal fluorescein staining score and visual-related function score (reading, driving at night, computer use, and watching television) as measured by the Ocular Surface Disease Index (OSDI), a validated instrument designed to assess the impact of dry eye upon vision-related activities. The safety and tolerability of SAR 1118 vs. placebo at 12 weeks will also be assessed. [1]

Evidence based evaluations