ThromboGenics's recombinant protein drug Jetrea (ocriplasmin) received US Food and Drug Administration (FDA) approval on October 18 for treating vitreous macular adhesion (VMA). The accompanying label imposes no restrictions and positions the Leuven, Belgium–based biotech firm for a launch in the US market in January. Around the same time, it expects to receive an opinion from the European Medicines Agency's Committee on Human Medicinal Products (CHMP). A positive result would pave the way for a European launch in March and trigger a €90 ($115) million payment from Alcon, the ophthalmology division of Basel-based Novartis. Alcon gained rights to the product outside the US last March, in a deal worth up to €375 ($479) million in upfront and milestone payments.
Novartis is now an obvious bidder for ThromboGenics, which is currently valued at about €1.3 ($1.6) billion. A combination of Alcon's third-quarter sales decline and the high price Novartis paid for the company—around $51 billion in successive tranches—has put pressure on the Swiss pharmaceutical firm to ensure its massive investment is a success. “For Alcon, it's a no-brainer,” one source, who wished to remain anonymous, says. “They have more to lose by not having the US rights.”
The more bullish analyst forecasts on Jetrea's potential put it in or around blockbuster territory. Jefferies, of New York, has forecast $875 million in sales, and KBC Securities, of Brussels, has forecast over €750 ($957) million in VMA alone, a condition that affects around 250,000 people. But it also has potential in additional eye indications, such as retinal venous occlusion, age-related macular degeneration (as an adjuvant therapy) and in a large fraction of diabetic macular edema (DME) patients. “Fifty percent of those people have VMA. Now you're talking about millions of people,” says KBC analyst Jan De Kerpel. The existing label allows its use in this population, but he says the company would probably obtain additional clinical evidence to support any marketing efforts here.
Jetrea, the first drug to gain approval for treating VMA, is a truncated form of two-chain human microplasmin, comprising just ∼230 amino acids of a catalytic domain. As a trypsin-like serine protease, it degrades various proteins found in blood clots, including fibrin, thrombospondin, laminin, von Willebrand factor and α2-antiplasmin. VMA, a condition associated with aging, occurs when the gel-like vitreous humor that fills the cavity between the lens and retina liquefies and contracts. This can result in complete detachment of the gel, which has no major consequences, but a partial vitreous detachment can result in damage to the macula, a part of the retina essential for central vision, and visual distortion. Jetrea, administered as a single injection, degrades the fibronectin and laminin fibrils that form residual connections between the vitreous gel and the retina. Vitrectomy (surgical removal of the vitreous gel) is the only available treatment at present, but the procedure can cause complications and is usually reserved for severe cases.
Preliminary evidence suggests that prior administration of Jetrea can improve the surgical outcome, but the drug will itself resolve the problem for some patients, without any need for surgery. In ThromboGenics's phase 3 program, 26.5% of eyes treated with ocriplasmin achieved VMA resolution, versus 10.1% of those that received a placebo injection (N. Engl. J. Med. 367, 606–615, 2012). The high placebo figure is thought to be due to a beneficial physical effect arising from an injection of a placebo solution. Ocriplasmin also met several secondary efficacy endpoints, including complete posterior vitreous detachment, closure of macular holes and improvement in vision.
The approval of the drug represents a neat bookend to the career of company founder and chairman Désiré Collen, who in 1980 discovered and developed with Genentech (now part of Basel-based Roche) the clot-busting stroke drug recombinant human tissue plasminogen activator (tPA), which generates around $494 million in worldwide sales each year.
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Sheridan, C. Belgian biotech's clot-buster approved for aging eyes. Nat Biotechnol 30, 1158 (2012). https://doi.org/10.1038/nbt1212-1158b