To no one's surprise, Genentech Inc.'s Lucentis (ranibizumab) received FDA approval for neovascular wet age-related macular degeneration, the leading cause of blindness in people older than 55.
The South San Francisco company already has begun shipping the injectable product, which is arriving on the wet AMD scene amid much anticipation. An inhibitor of the vascular endothelial growth factor (VEGF), it is designed to inhibit the formation and leakage of new blood vessels in the back of the eye, the primary cause of central vision loss associated with this disease.
"The approval of Lucentis marks a major advance in the treatment of wet AMD," Quinton Oswald, Genentech's vice president of tissue growth and repair, said in a conference call. He added that the product is the first "to not only maintain, but improve, vision."
That reversal of vision loss underscores the hype, and Bret Holley, an analyst with CIBC World Markets Corp. in New York, noted that Lucentis' label is "very in line" with expectations on The Street. The FDA cleared the highest possible dose, 0.5 mg, and indicated its use in all types of the disease.
Lucentis will cost $1,950 per vial, and Oswald estimated that most patients would require five to seven injections per year. Such mean annual usage would equate to $9,750 to $13,650 per patient. About 155,000 Americans are diagnosed each year with AMD, and about 10 percent have wet AMD.
Holley estimated Lucentis sales would reach $85 million for the second half of this year and eventually grow to $950 million by 2010. "We think those are very achievable numbers," he told BioWorld Today, "given the magnitude of benefits seen with the drug."
The biologics license application was filed six months ago, earlier than planned, and received priority review. (See BioWorld Today, Jan. 3, 2006.).
The submission was based largely on efficacy data from two Phase III trials that showed that 95 percent of Lucentis-treated patients maintained their vision, and more than a third experienced a clinically significant improvement, as vision improved by at least three lines (or 15 letters) on the study eye chart at one year. In one of the studies, called MARINA, Lucentis patients experienced an improvement from baseline of 6.6 letters at two years compared to a loss of 14.9 letters in the sham group. In the other study, called ANCHOR, Lucentis patients experienced an 11.3-letter gain from baseline at one year, on average, compared to a 9.5-letter loss in the control group treated with Visudyne (verteporfin, from QLT Inc.).
Holley said the collective findings represent "the most compelling data" in this space to date. "That I can say with certainty," he added. "And I think based on that, until a better treatment comes along, it's the standard of care."
Oswald was equally bullish about Lucentis' place among other existing drug treatments, noting that its approval "sets a new standard for treating wet AMD." He called the market's latest entrant "a vast improvement" over the rest.
The competitive landscape includes the Visudyne photodynamic therapy and Macugen (pegaptanib, from OSI Pharmaceuticals Inc. and Pfizer Inc.), which like Lucentis blocks VEGF. Also used in the wet AMD space is Genentech's blockbuster cancer drug Avastin (bevacizumab), another VEGF inhibitor. Some analysts have expressed concern that Avastin's off-label use could cut into Lucentis' upside, but Holley, whose firm does not make a market in Genentech, discounted such worries.
"The reimbursement for this drug, I think, is going to be universal," he said. "So I think in an environment where reimbursement is not a problem and patient costs are not high, I don't see a lot of intravitreal Avastin use, given that it's not approved for the indication."
Other anti-VEGF products in late-stage development include Evizon (squalamine, from Genaera Corp.), Cand5 (from Acuity Pharmaceuticals Inc.) and Sirna-027 (from Sirna Therapeutics Inc.).
The FDA recommended monthly injections of Lucentis. If that schedule is not feasible, treatments can be reduced to once every three months after the first four monthly injections, though that lowers efficacy compared to continued monthly dosing to a loss of about five letters (one-line) in visual acuity benefit over the following nine months.
Genentech agreed to post-approval studies to further evaluate dosing frequency matters and other issues. In addition, the company already is following patients from two ongoing wet AMD studies. Other development efforts on the drug are focused on diabetic macular edema.
The FDA noted that serious adverse events were rare and often related to the injection procedure, including endophthalmitis, intraocular inflammation, retinal detachment, retinal tear, increased eye pressure and traumatic cataract.
Novartis AG, of Basel, Switzerland, has exclusive commercial rights outside the U.S., and European approval for wet AMD is expected next year.
Investors responded favorably to the news, with Genentech's shares (NYSE:DNA) gaining $1.67 to $81.80.