EP Vantage Interview - ThromboGenics eyeing approval success

With a marketing application submitted to the FDA this week and a regulatory review already underway in Europe, ThromboGenics’ ocriplasmin has started the final lap. Potentially the first non-surgical treatment for the eye disorder vitreomacular adhesion, the Belgian drug developer hopes to be launching its first product by the end of 2012.

The company reported results from two successful pivotal trials more than 12 months ago; Patrik De Haes, chief executive, anticipates an FDA advisory committee hearing to review the drug in the summer. While the verdicts are awaited the company will keep busy building its commercial outfit in the US and searching for a commercialisation partner in Europe; Mr De Haes tells EP Vantagehe expects to deliver a deal ahead of the regulatory decisions.

Taking the exam

The European filing for ocriplasmin, formerly called microplasmin, was made in October and Mr De Haes says he expects to receive the first questions from the regulator in early February. In the US, ThromoGenics has not sought a priority review; the two assessments running concurrently would have been a big demand on the company.

“We are a small club, it might not have been good for both filings” Mr De Haes says, pointing out that only a small minority, around a third of companies, get approval in the abbreviated six month time frame.

A meeting was held with the FDA a year ago in an attempt to square away CMC (chemistry, manufacturing and controls) questions, a common area for trip up. Now the company must wait for the verdicts.

“We have basically done everything we could to deliver a quality file with the means and people we have. We have studied for the exam. Now we have to take it,” he says.

Closing the hole

Potentially removing the need to operate – the only treatment option currently available to treat vitreomacular adhesion (VMA) - is one of the big selling points of ocriplasmin. The condition causes the vitreous gel in the eye to adhere to the macula, at the centre of the retina. This can cause “traction” when people move their heads, which activates the retina, causing disturbances in vision. In extreme cases holes can tear in the macula, causing partial blindness.

An onerous surgery procedure called vitrectomy to detach the gel is carried out in extreme cases; many patients live with the effects of traction.

Ocriplasmin is administered via a single injection into the eye. The drug is a truncated form of plasmin, a naturally occurring enzyme that dissolves protein formations.

Across two pivotal studies involving 652 patients the primary endpoint, non-surgical resolution of focal VMA, was met after one month. Six-month follow up data show that 41% of patients with full thickness macular holes achieved closure compared with 17% on placebo, while 58% of patients with a smaller hole saw closure, compared to 20% of placebo (ThromboGenics eyeing triumph as first pivotal trial succeeds, April 20, 2010).

“Clinically this is a very attractive treatment because you don’t have to do the operation,” says Mr De Haes. “The clinical data, wherever we present them in Europe or the US, are seen as very innovative.”

Good chance

Not all patients completely respond to ocriplasmin – for example in those with diabetic retinopathy or a condition called macular pucker response rates are much lower. Encouragingly, however, the company has some early evidence that for those that still need surgery after treatment with ocriplasmin, the procedure is shorter and less onerous.

Regulators meanwhile wanted the pivotal trials to enrol all patients with VMA, whatever the underlying condition, and as such ThromboGenics has applied for a broad label.

With few safety issues – an increase in “floaters” was the main adverse effect of the injection – and lack of other options, ocriplasmin appears to have a good chance of convincing regulators it has a place on the market.

Financial analysts remain fairly divided on what the VMA opportunity is worth to ThromboGenics; the company has been guiding to a price of around €2,000 for the one-off injection.

Analysts reckon treating macular adhesion alone could generate anything from €250m to €800m in peak sales. Bigger potential lies in the company’s ability to pin down efficacy in other conditions or subgroups; VMA is thought to be involved in a number of back of the eye conditions, perhaps playing an exacerbating role.

Deal

Mr De Haes says a trial in diabetic retinopathy is likely to start next year, while data should emerge towards the end of 2012 from a study in age-related macular degeneration testing ocriplasmin in combination with Lucentis.

“A third of patients with AMD have adhesion. If we can take the adhesion away with our drug, we might be able to improve the efficacy of Lucentis,” Mr De Haes says.

A European marketing partner for the product should also emerge this year. In the US the company has elected to promote alone – a sales force of 50 is being targeted and executives involved in the launch of Lucentis hired.

“We think the US is easier to handle ourselves. Europe is extremely complex particularly in terms of market access. If we work together with a partner, it should be a more efficient way for us to launch the product,” Mr De Haes says. “We have good interest. It will be a player that is known in the market.”

Attractive option

ThromboGenics also has plans to beef up its ophthalmology franchise, through internal programmes under development and externally sourced projects.

“Unfortunately many others also have that plan. Ophthalmology is a very competitive arena,” he says.

This fact could make ThromboGenics itself an interesting proposition. Mr De Haes hopes partnering talks do not turn into takeover talks; he says the company is keen to execute on what they see as a very “efficient” way of launching ocriplasmin.

He says the plan to bring in partners outside the US should help alleviate investors’ caution around new drug launches, which has certainly become more apparent in the last year. With a market value of €591m ($811m), a certain amount of confidence in ocriplasmin already exists.

However, shares in the company have declined 20% across the year. Getting a big partner on board and approvals under its belt would mean a very different ending for 2012.

Share This Article