Just as others have been making good on their promises to act "by year-end," Genentech Inc. and XOMA Ltd. submitted the biologics license application for Raptiva as a treatment for moderate to severe psoriasis.
The drug may hit the market after Cambridge, Mass.-based Biogen Inc.'s Amevive (alefacept), since the FDA told the company in September that a review is expected to be complete in six months and Genentech/XOMA anticipate a 10-month review for Raptiva (efalizumab) - which also is up against Amgen Inc.'s Enbrel (etanercept), used off-label for psoriasis. (See BioWorld Today, Sept. 16, 2002.)
"To me it's definitely the No. 3 player," said Martin Auster, analyst with SunTrust Robinson Humphrey in Atlanta, which does not own a position in Genentech or XOMA.
"Raptiva will be tougher to find a niche for," he told BioWorld Today. "That's the problem. With Amevive you have the option of going on it for 12 weeks and then off for 12 weeks, and Enbrel has its good reputation," thanks to its use as a rheumatoid arthritis treatment.
"People have an understanding and trust of it, and it has the best data so far, frankly," he added.
"I don't think anyone has any numbers [on Enbrel use against moderate to severe psoriasis]," Auster said. "I wouldn't say it's being used a lot, but certainly it's going to pick up with the supply coming on." This week, the FDA gave its approval to Amgen's manufacturing facility for Enbrel in Rhode Island.
Auster noted that Enbrel already is approved for psoriatic arthritis, which "is probably the best way to get reimbursed for psoriasis. Enbrel's going to have at least a 50 percent share of the market looking at 2005. Does it need approval in [moderate to severe] psoriasis to drive 'scrips? I don't think so."
The market isn't as large as some believe, Auster said, estimating about 150,000 patients in the U.S. on systemic therapies for psoriasis.
"There just aren't that many patients, and you reach a certain stage with this disease where you accept it and it's part of you," he said, particularly in the moderate forms and in younger patients.
Malvern, Pa.-based Centocor Inc.'s Remicade (infliximab), approved for Crohn's disease and rheumatoid arthritis, also is being developed for psoriasis and already is used off label for that indication.
Raptiva is a humanized monoclonal antibody and targeted T-cell modulator, designed to inhibit the inflammatory cascade in psoriasis, said Tara Cooper, corporate affairs manager for South San Francisco-based Genentech. Specifically, it works by blocking the binding of LFA-1 to ICAM-1
"The key thing is that it inhibits T cells from binding to key cells in the psoriasis cascade, as opposed to depleting T cells," she told BioWorld Today.
Genentech, with XOMA, of Berkeley, Calif., is backing the BLA with data from Phase III data disclosed this fall. Geneva, Switzerland-based Serono SA, the partner for Raptiva sales outside the U.S., is expected to file for approval there in the first quarter of next year.
Genentech thus finds itself with two drugs, Raptiva and Xolair (omalizumab), that could win approval near the end of next year.
"That's up to the FDA but they're both on the standard [regulatory] clocks," Cooper said.
Xolair, which won marketing approval in Australia in June, is a first-in-class monoclonal antibody targeting IgE, which, in allergic asthma patients, binds with allergens to mast cells, triggering the release of histamine and leukotrienes.
Genentech, with partners Novartis Pharma AG, of Basel, Switzerland, and Tanox Inc., of Houston, submitted a BLA amendment including more data earlier this month from a trial that was expanded at the FDA's request. (See BioWorld Today, Dec. 20, 2002.)
The potential dark cloud is Avastin (bevacizumab), Genentech's monoclonal antibody for use in combination with chemotherapy against breast cancer, for which the company is expected to disclose Phase III data in mid-2003. The FDA has told Genentech the data would have to be "very significant" to justify a filing.
This fall, Genentech said Avastin (bevacizumab), an antibody directed at vascular endothelial growth factor, missed its primary efficacy endpoint of progression-free survival in relapsed metastatic breast cancer. Two Phase III trials of Avastin in colorectal cancer have completed enrollment. (See BioWorld Today, Oct. 11, 2002.)
Also in the Genentech mix is Tarceva, a small-molecule, epidermal endothelial growth factor receptor for non-small-cell lung cancer being developed in Phase III trials in a three-way deal with OSI Pharmaceuticals Inc., of Melville, N.Y., and Roche Holdings Inc., of Basel, Switzerland.
"I don't think anyone has huge expectations for either [Avastin or Tarceva]," Auster said. "Their likelihood of approvability is not what it was 12 months ago."
In the near term, he predicted, investors will take more note of slowing growth of sales for Rituxan (rituximab), Genentech's blockbuster drug for non-Hodgkin's lymphoma. Auster predicted a 37 percent growth in 2002 sales, topping out at $1.1 billion, but forecast slower growth - probably in the high teens - in 2003, when he put sales at $1.3 billion.
"The stock is kind of soft in the first part of 2003 as people focus on Rituxan, but then they will start looking out a little longer" to the pair of potential approvals, Auster said.
In separate news, XOMA said Cambridge, Mass.-based Millennium Pharmaceuticals Inc. bought about 1.44 million newly issues shares for about $7.5 million, pursuant to a deal made in November 2001, and Millennium is committed to buy another $37.5 million in shares at XOMA's option during the next 18 months.
That agreement is for the development of a pair of Millennium's biotherapeutic agents, CAB-2 and LDP-01, for certain vascular inflammatory indications. Under the terms, which included the investment deal, XOMA pays for development through completion of Phase II trials, after which it has the option to choose between further participation in the development program and eventual profit sharing, or future royalty and milestone payments. (See BioWorld Today, Nov. 27, 2001.)
The news about Raptiva was released after the market closed Monday. Genentech's stock (NYSE:DNA) fell $1.06 Tuesday and gained 1 cent Thursday to close at $34.90. XOMA's shares (NASDAQ:XOMA) fell 10 cents Tuesday and 16 cents Thursday, closing at $4.27.