Santen launches new preservative-free combination eye drop in the UK

Santen recently launched fixed-combination tafluprost and timolol (TAPTIQOM) in the United Kingdom.

The recently developed, preservative-free, fixed-dose combination of 0.0015% prostaglandin F_2α analog (tafluprost) and beta-adrenergic antagonist (0.5% timolol) is designed to lower intraocular pressure (IOP). TAPTIQOM® is available in single dose containers and is administered as one drop once-daily.

According to a review study published in Advances in Therapy in 2014, patients with high IOP responded well to TAPTIQOM®, which delivered IOP reductions of up to 40% (>13 mmHg) versus baseline and even beyond this in some cases. Specifically, two Phase-III studies (n=484) revealed that TAPTIQOM® delivered IOP reductions of between 28% and 40% (dependent on baseline) at 3 months. The Advances in Therapy review included double-masked, controlled clinical trials carried out with the following combination products: Xalacom^®, DuoTrav^®, Ganfort^® and TAPTIQOM® and found that the reduction in IOP was similar to that of other prostaglandin–timolol fixed-combination products used in open-angle glaucoma and ocular hypertension.

Reducing hyperaemia and improving tolerability

Although questions have been raised in the ophthalmic community around the benefit of adding a further combination product with similar efficacy to the market, The European Glaucoma Society 2014 guidelines do state that when selecting glaucoma therapy, consideration should be given not only to IOP lowering but also to tolerability, adherence and cost.

Despite similar IOP-reducing capacities, when compared to previous controlled and double-masked clinical trials with DuoTrav^® (Alcon, Fort Worth, USA) and Ganfort^® (Allergan, Irvine, USA), the review revealed that TAPTIQOM® caused fewer superficial ocular side effects and less conjunctival hyperaemia. Indeed, the frequency of reported treatment-related adverse event conjunctival / ocular hyperaemia in clinical studies was low (7% of patients). In addition, in the small number of TAPTIQOM® treatment-related hyperaemia cases, the condition was mild and was associated with discontinuation of therapy in just 1.2% of patients.

Next: Differences explained

The mechanism of IOP reduction is similar for all the combination products that were assessed in the review; timolol induces the reduction of aqueous humor production, and the enhancement of aqueous humor outflow occurs via FP prostanoid receptor activation, induced by the prostaglandin.

Explaining the differences

Plausible explanations for the differences in side effects between the fixed-combination products are as follows:

·       All prostaglandin analogs are rather selective FP prostanoid receptor agonists, however, some subtle differences do exist, which may explain the variance in side effects. As timolol is well known for inducing no or minimal hyperaemia (or irritation), it seems probable that the condition is caused mainly by the prostaglandin analog. Unlike the other combinations reviewed, TAPTIQOM® stimulates EP₃ receptors, which can be expected to cause vasoconstriction and thereby counteract part of the vasodilation caused by the FP receptor stimulation, explaining why the hyperaemia caused by TAPTIQOM® appears to be less frequent and less severe than that of Ganfort^® and DuoTrav^®.

·       TAPTIQOM® are preservative free drops – this feature could be what causes the eye drops to exert relatively little ocular irritation. On the other hand, taking into account the relatively short period of exposure, it is as likely that the improved tolerability profile of TAPTIQOM® is due to the active ingredient. Nevertheless, the absence of preservative will certainly improve the long-term tolerability of TAPTIQOM®. It is important also to bear in mind that European Glaucoma Society 2014 guidelines also highlight that the chronic use of medications containing preservatives may cause or exacerbate ocular surface disease.

Gaining EU approval

TAPTIQOM has been approved in Germany since December 2014 for adults with open-angle glaucoma or increased IOP (ocular hypertension) and is now indicated in the UK for the IOP reduction in adult patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical monotherapy with beta-blockers or prostaglandin analogues and require a combination therapy, and who would benefit from preservative free eye drops.

Next: Promises for the future

Craig Wallace, Santen General Manager UK & Ireland believes that TAPTIQOM® now offers the next step in preservative-free IOP reduction because it combines powerful efficacy with good ocular tolerability, which supports patient adherence to therapy and is an ideal solution for patients who are insufficiently responsive to topical monotherapy with prostaglandin analogues or beta-blockers, requiring combination therapy. The drug may hold particular promise for patients with hyperaemia in particular, a common side effect of anti-glaucoma therapy and a key reason for patients discontinuing treatment with prostaglandin analogues. TAPTIQOM ® also offers the benefit of being competitively priced in the UK.