Physician Views: A landmark approval in glaucoma beckons – but commercial challenges may await

Aerie Pharmaceuticals has pulled off a number of coups where its experimental glaucoma treatment Rhopressa is concerned. Having seen the drug fail to better the beta-blocker timolol in an initial Phase III trial (the ROCKET-1 study), Aerie successfully petitioned the FDA to allow it to modify the endpoint of a second, ongoing trial. Having achieved its primary endpoint in ROCKET-2, Rhopressa successfully negotiated an advisory committee meeting last week, with a panel voting 9-1 in favour of approval. Echoing the tone of briefing documents published by the FDA ahead of the meeting, the panel agreed that Rhopressa's efficacy outweighs its risks. The agency will make a final approval decision on or before February 28, 2018, while Aerie expects to file Rhopressa in the EU next year, having been required to undertake some additional safety studies.

Despite a positive AdCom vote, however, shares in Aerie fell 2 percent in response; reflecting a view, perhaps, that as regulatory approval moves closer – in the US at least – commercial questions will be asked with more intensity. On one hand, Rhopressa should become the first new treatment for glaucoma to reach the market in two decades; on the other, the primary endpoint of Aerie's two pivotal-stage trials was to show non-inferiority against timolol – a well-established therapy available cheaply as a generic. Against a relatively low bar, sceptics will argue that Aerie was also forced to cherry-pick its data to find a patient subgroup where Rhopressa is effective. Furthermore, while the FDA nor its panel members were overly critical of Rhopressa's side-effect profile, there remain a number of toxicity concerns.

To better ascertain how Rhopressa may be used for the treatment of glaucoma, we are therefore snap-polling US and EU ophthalmologists with the following questions…

In a Phase III study, the experimental agent Rhopressa (netarsudil ophthalmic solution) – when dosed both once and twice daily – achieved its primary efficacy endpoint of demonstrating non-inferiority compared to twice-daily timolol at lowering intraocular pressure (IOP) in patients with glaucoma or ocular hypertension. The primary efficacy endpoint evaluated subjects with pre-study baseline intraocular pressure (IOP) of above 20 to below 25 mmHg (millimetres of mercury). How compelling is this result?

Not compelling

Marginally compelling

Moderately compelling

Very compelling

Extremely compelling

In another Phase III study, Rhopressa was found to be inferior to timolol at lowering IOP in patients with baseline IOPs of ≥ 25 mmHg. Assuming Rhopressa is approved for use in patients with IOP of above 20 to below 25 mmHg, would this lack of efficacy in patients with higher IOP deter your overall usage?

No – different patient population

Yes – slightly

Yes – moderately

Yes – significantly

Yes – very significantly

In a six-month, 700-patient safety study, the most common adverse event associated with Rhopressa was hyperaemia – or eye redness – which was reported in 48% of patients, versus 7% with timolol. The degree of severity was measured per physician-assessed bio-microscopy and deemed to be mild, sporadic and largely transient. However, in relation to hyperaemia on Rhopressa's proposed US label, the FDA has proposed removal of the 'mild' severity language.

To what extent will this side effect deter use of Rhopressa in a real-world setting?

No meaningful impact

Minimal impact

Moderate impact

Significant impact

Very significant impact

During an FDA advisory committee meeting last week, cornea verticillata was the side effect associated with Rhopressa (incidence rate of 11.7% versus no cases with timolol) that was discussed most prominently. To what extent does association of cornea verticillata concern you/will impact future utilisation of Rhopressa?

No impact

Minimal impact

Moderate impact

Significant impact

Very significant impact

To what extent will the cardiovascular properties of timolol (it demonstrated greater magnitudes of reductions in both heart rate and blood pressure versus Rhopressa in two Phase III studies) result in you retaining utilisation of this older therapy at the expense of Rhopressa?

No impact

Minimal impact

Moderate impact

Significant impact

Very significant impact

Results and related analysis will shortly be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.

As always, FirstWord would very much like to receive your feedback and suggestions. Note: FirstWord Polls are powered by Medefield MedePolls, a fast-turnaround service to conduct instant polls of up to five questions with guaranteed samples that include physicians from dozens of specialties and over 100 markets. To conduct this poll with a different audience, or an entirely different poll, contact us at info@firstwordpharma.com.

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