ThromboGenics Delays Diabetic Retinopathy Study; On Track To File Ocriplasmin For Retinal Adhesions

Belgian company focuses on filing orciplasmin for U.S. and EU approval, and preparing for commercialization.

Belgian biotech ThromboGenics NV has put back until early next year the start of a further clinical trial of its lead product, ocriplasmin, in a new indication, early diabetic retinopathy, while it focuses on submitting U.S. and EU marketing applications for the treatment of symptomatic vitreomacular adhesion (VMA) including macular holes, its first indication.

Although the delay in researching new indications might suggest it would benefit from having a partner, CEO Patrik De Haes was adamant that ThromboGenics would continue to work alone, at least in the development and commercialization of ocriplasmin (previously known as microplasmin) in the U.S. and the top-five EU markets for VMA, a sight-threatening condition which leads to central blindness - a black spot in the center of the visual field.

"The U.S. represents at least 60% of the market for ocriplasmin, and with only 2,000 retinal surgeons there, and a similar number in Europe, we really want to market this product ourselves," De Haes said in an interview.

De Haes confirmed that approval submissions for ocriplasmin in the EU and U.S. were on track and expected to be submitted by the end of the year, with first launches expected in late 2012. There are about 500,000 potential patients in the U.S. and Europe for ocriplasmin therapy, the company estimates. Partners, however, are being sought to market ocriplasmin in other countries around the world.

Ophthalmological businesses have been under the spotlight of late, with new companies, like KalVista Therapeutics Ltd., entering the sector (Also see "U.K. Ophthalmology Spin-Out Raises £8m For DME Programs" - Pink Sheet, 22 Aug, 2011.)), and big pharma companies like Sanofi SA and GlaxoSmithKline PLC taking renewed interest in the therapeutic area. But the cost of prescribing some new ophthalmologicals, like Roche Holdings/Novartis AS' Lucentis (ranibizumab), also has been challenged (Also see "Lucentis And Avastin Stack Up In CATT, Forcing Genentech/Novartis To Play Defense" - Pink Sheet, 28 Apr, 2011.)).

De Haes accepted that ThromboGenics was entering an increasingly competitive sector, but pointed out that, upon approval, ocriplasmin would become the first drug to be marketed for VMA. The company has the financial resources to support its strategy: It raised €56 million ($75 million) in a private placement in December 2010, and at the end of the second quarter this year had €96.4 million in cash (Also see "Four EU Biotechs Raise Extra Funds In Year-End Scramble" - Pink Sheet, 3 Dec, 2010.)).

A high proportion of U.S. retinal disease specialists apparently have listened already to scientific presentations on ocriplasmin. The company plans to concentrate its marketing efforts on recruiting medical liaison experts to explain the medical rationale for ocriplasmin, and on developing relationships with payors - it expects to price ocriplasmin at around 2,000 to 3,000 dollars/euros per injection, De Haes revealed.

At that price ocriplasmin, which is administered once by intravitreal injection, compares favorably with the surgical alternative, vitrectomy, which costs around $5,000 per operation in the U.S., De Haes said. There are data showing that, currently, U.S. patients undergo on average 2.9 surgical procedures for VMA, increasing the cost and improving the comparison with ocriplasmin even further.

Jeffries analysts also noted that U.S. reimbursement procedures and physician uptake should be eased by the recent recognition of VMA as a distinct disease, which has being given its own code in ICD-9-M.

Thin Strands Pull On The Retina

De Haes explained that the vitreous humor gel inside the eye usually is in close contact with the retina, but as a person gets older, the gel retracts and is connected to the retina only by thin strands of fibronectin and laminin. If these don't loosen, as is the case in VMA, these strands pull on the retina, causing blurred vision. In more severe cases, holes form in the macula (the central part of the retina) and the condition progresses to vitreomacular traction syndrome (VMT).

Macular holes cause central blindness, which is extremely worrying for patients. Ocriplasmin is one of the few substances that can digest the strands and allow separation of the gel from the retina.

Clinical data were presented last year from two Phase III clinical studies involving 652 VMA patients, which showed ocriplasmin resolved adhesions in around 30% of patients treated and improved visual acuity. On Aug. 22, at the annual meeting of the American Society of Retina Specialists in Boston, U.S. researchers presented further subgroup analyses of the two trials, showing that ocriplasmin reduced adhesions in patients with the more severe condition, VMT. Also, in 153 patients treated for full-thickness macular holes, those holes were still healed up six months later in 40.6% of ocriplasmin-treated patients, compared with 17% of placebo-treated patients.

The diagnosis of VMA has benefited enormously from the development of a new imaging technique, optical coherence tomography, which uses infrared light to visualize the different cell layers in the retina, at a much higher resolution than MRI or ultrasound.

AMD Study Underway

Ocriplasmin is being studied in other retinal diseases, and De Haes noted that a Phase II trial is underway in acute macular degeneration. VMA is present in around a third of AMD patients, and it has been suggested that if retinal traction is removed, there might be a reduction in VEGF levels in the eye, leading to a reduction in patients' requirement for Lucentis or other VEGF antagonists.

In diabetic retinopathy, it has been suggested that the vitreous humor gel acts as a scaffold into which disruptive blood vessels grow, and cutting the strands might take the gel away from the retina, alleviating the condition. The hypothesis will be tested in a study of patients with early diabetic retinopathy, including those with diabetic edema, expected to start early next year.

- John Davis ([email protected])