News@Nature AMD article
This article is mostly about Lucentis. However, at the end of the article the authors mention there is still room in the AMD market, given the shortcomings of Lucentis dosing. Several companies with drugs in development for AMD could benefit from I-vation-type devices in getting an edge (eg Pfizer's AG-13958, Regeneron's VEGF Trap, or Novartis' PTK787), both in terms of convinience and in terms of maximizing a given drugs' efficacy, IMHO. One possible exception could be siRNA, but it is still too early to tell if siRNA technology is likely to produce an approvable product. I would be surprised if it takes long before SRDX gets its first licensing agreement, but I would also be interested in hearing what others think. BTW, I don't think there is good economic incentive for Genetech to pursue sustained release until IVT-injected Lucentis market share is threatened.
Published online: 1 September 2006;
Companies eye slice of age-related macular degeneration market
Genentech has the first treatment that restores sight in patients with AMD, but it may face competition from one of its own drugs.
Emily Waltz
Genentech's new antibody therapy Lucentis (ranimizumab), approved in June, has the potential to dominate the market for a common eye disease. In a few years, however, it may face direct competition from Avastin (bevacizumab), a sister drug made by the same company. Meanwhile, OSI Pharmaceuticals and QLT, which already have drugs approved for the same eye disease, are trying to consolidate their market positions. As yet, several other potential competitors with drugs in phase 2 development for the same indication have not demonstrated any advantages over Lucentis.
On June 30 the US Food and Drug Administration (FDA) announced it had approved Lucentis, a treatment for wet age-related macular degeneration (AMD). The drug is administered as an injection into the eye and is a humanized antibody FabV2 fragment that targets vascular endothelial growth factor (VEGF), a protein associated with growth and leakage of blood vessels that causes vision to decline.
Lucentis, which is made by S. San Francisco-based Genentech, is the first approved treatment to restore sight in a significant percentage of patients afflicted with the disease. AMD is a major cause of blindness in people over 50 years old. Until now, drugs approved for AMD could only slow the progression of the disease, rather than reverse it. [note, Lucentis only partially restores vision in a subset of patients, so there is room for improvement here as well]. But in phase 3 clinical studies of Lucentis, vision improved in more than one third of the individuals who took it.
Experts say Lucentis will likely steal a significant market share from the two AMD treatments on the market: Pfizer/OSI Pharmaceuticals' aptamer Macugen (pegaptanib) and Novartis/QLT's small molecule Visudyne (verteporfin). Lucentis may also discourage companies from developing new therapies. "The success of Lucentis has raised the bar so much that it makes it difficult to come up with a drug that's better," says Julia Haller, a professor of ophthalmology at Johns Hopkins University in Baltimore.
But physicians are discovering on their own that Genentech's approved cancer drug, Avastin, an anti-angiogenic antibody that binds VEGF, may work for AMD just as well and just as safely as Lucentis —and for a fraction of the price. Industry insiders say that if independent investigators complete enough safety and efficacy studies, off-label Avastin prescribed for AMD may become Lucentis' greatest competitor (Box 1).
However, analysts such as Joshua Schimmer, at SG Cowen in New York, believe Lucentis will likely capture 65% of the $1-billion US market. Indeed, Lucentis' arrival on the market will be a major blow to Macugen, which was developed by OSI Pharmaceuticals and is marketed by Pfizer. Researchers say the difference between the drugs may be the amount of VEGF each drug inhibits. Although Lucentis can bind and inhibit all the active molecular forms of VEGF, Macugen binds to only one form of VEGF, called VEGF-165."Macugen is effective but not as effective as Lucentis," says Tony Adamis, chief scientific officer of OSI. "Lucentis' data is so impressive...even I have to admit that."
In August, OSI announced that due to competition, it would suspend or curtail all R&D for eye diseases, except on Macugen. OSI's Adamis says he believes Macugen could find a spot on the market as a maintenance drug—something individuals can take after they've reaped the benefits of Lucentis. Based on their interpretation of Genentech's data, OSI theorizes that patients could take Lucentis for their first three doses, and then switch to Macugen, which costs about half as much, and, on average, is injected less frequently. The company has set up a clinical trial to test this proposal.
Many experts, however, say OSI's theory is based on little or no data, and is a last attempt to salvage their product. "They are trying to use a marketing ploy to feed off ophthalmologists who are not in the know," says Peter Campochiaro, a professor of ophthalmology at the Wilmer Eye Institute at Johns Hopkins. "They've been pretty shameless."
Lucentis' other approved predecessor, Visudyne is a treatment called photodynamic therapy, in which the drug is injected into the bloodstream and activated in the eye by a light beam. Like Macugen, it can slow the progression of AMD, but usually cannot reverse it. "It's hard to see it playing a meaningful role going forward," says Schimmer. Visudyne may be useful for individuals who cannot endure an injection in the eye, he says. It may also be used as a combination treatment with Lucentis, although data so far have not supported this treatment regimen, he says.
As Lucentis edges out drugs already on the market, it may also douse enthusiasm and funding for some early-stage AMD candidates. Just two months after Genentech announced in July 2005 its phase 3 results for Lucentis, Alnylam Pharmaceuticals, a biotech company in Boston, announced that it would halt development of its AMD drug because of competition.
But others persevere. Among the most promising candidates in the development pipeline, some experts say, is the VEGF Trap by Regeneron Pharmaceuticals. Scientists believe the drug works by binding more effectively with VEGF, thereby blocking VEGF receptors. A phase 1 study showed that a single injection lasted at least six weeks.
Although Lucentis is one step ahead of competitors, it has some drawbacks, and industry insiders say there is still some room on the market for new products. Eye injections are rough on patients and carry risk. Lucentis must be injected into the eye every month for the first four months, and then at varying frequency afterward. A drug that lasts longer or can be administered less invasively and less frequently than Lucentis has potential.
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