One of its virtues is that it binds to TNF-a with high affinity. Another is the absence, thus far, of any sign of immunogenicity,
meaning that it fails to provoke an autoimmune attack. Its production process, using fermented E. coli, is also a competitive edge. It costs just 5-10 percent of the alternative technique using mammalian cell cultures. In addition,
the FAbs are modified by pegylation. Molecules of polyethylene glycol (PEG) are attached to improve their pharmacokinetics,
prolonging their half-life to 12-15 days, thereby lowering the drug's dosing frequency. This potential for a once-a-month
injections is what Sena Lund, senior analyst at Cathay Financial, says "should be its key advantage over established products."
Mu-opioid antagonist Entereg "could be very big," says David Goldstein, "because it stays in the gastrointestinal tract."
Plus, the fact that it is not absorbed, he says, makes it "totally safe."
Initially submitted for postoperative ileus and accepted for review this quarter, Entereg "eliminates anesthesia-induced nausea,"
according to Goldstein, "so you can feed patients and get them out of the hospital a day earlier." It has other uses as well,
including reversing the constipation that opioids tend to promote. But, because it stays in the gut, "It doesn't affect the
opioid's analgesic—or, in the case of methadone and certain other drugs, its psychomimetic—effects." It may also be used for
treating irritable bowel syndrome and idiopathic constipation.
Merck's vaccine for human papillomavirus (HPV), the most common sexually transmitted disease, Rauch believes "could eliminate
cervical cancer," which kills 4,000 women in the United States and nearly 250,000 worldwide every year. It is also, Moskowitz
says, "very important for the prevention of genital warts in men and women." A regulatory filing is expected in the second
half of 2005.
Lucentis AMD [ranibizumab]
Age-related macular degeneration (AMD)—the leading cause of blindness in Americans over 50—is a problem that grows as the
population grays. Every year, 200,000 cases crop up in the United States, and half a billion are diagnosed around the world.
By 2025, 11 million people could be affected. Today, 6-10 percent develop wet AMD, characterized by the growth of abnormal
blood vessels. Just one in four, those with certain subtypes, can be treated. Lucentis, Samet notes, is one of "many products
targeting VEGF-mediated angiogenesis by a variety of novel molecular techniques, including monoclonal antibodies and iRNA."
But it is just one of two expected to be monotherapies for all subtypes of wet AMD. The other is Macugen (next).
Lucentis is injected directly into an anesthetized eyeball. Because it is a fragment of a larger anti-VEGF antibody, it can
deeply penetrate to better block the growth of new blood vessels and stem leakage from existing ones. Two Phase III trials
are ongoing. Data are expected in the first half of next year, and a filing is possible before year's end.
Macugen is like Lucentis in attempting "to inhibit VEGF-mediated vascularization within the retina leading to leaky blood
vessels," Samet says. Unlike Lucentis, Macugen is an oligonucleotide molecule or aptamer. But both work to block the protein
that effects blood vessel growth.
There seems to be no doubt that Macugen has broader application than the standard treatment, QLT's Visudyne (verteporfin).
There also appears to be little question that it is well tolerated and safe. What remains at issue is whether it is more effective
than Visudyne. Another question is its comparative convenience. Like Lucentis, Macugen requires intraocular injection. Visudyne
is administered via a subcutaneous injection, then stimulated by a cold laser. Macugen has been given priority review status
by regulatory authorities in the US and Canada. Approval could come soon enough for a first-quarter launch in 2005.