From Promise to Payoff - Pharmaceutical Executive


From Promise to Payoff

Pharmaceutical Executive


The race for the first oral treatment

In the treatment of multiple sclerosis, advances in convenience or tolerability can make a big difference in sales. Interferon beta 1-a (Avonex from Biogen Idec) is an established therapy for MS relapse prevention and, in the US, a first line treatment for newly diagnosed patients. In a new pegylated form, patients can look forward to fewer, less painful injections. Avonex is currently injected once a week in a doctor's office. The new longer lasting drug will not require the same large-bore needle for intramuscular injections. Instead, patients will give themselves a subcutaneous shot every other week or perhaps once a month. "We expect it do very well, with sales of about $1.5 billion by 2018," says Andrea Witt, an analyst at Decision Resources.

Even as current patients look forward to self-injections, drugmakers are racing to launch the first oral MS drug in this $8.6 billion IV-only market. Oral cladribine, a new formulation of anti-leukemia injectible Leustatin from EMD Serono, an affiliate of Merck KGga, was leader of the pack until FDA issued a "refuse to file" letter in November, which puts all market plans on hold. The chemical promises better efficacy than the interferons but worrisome side effects, including headache, upper respiratory tract infections, and nausea. "Oral cladribine will have efficacy between these two broad classes of drugs—better than the interferons and Copaxone, but not as good as Tysabri," Witt says. "However, it will have the oral formulation—but with the bad side effects, it's not going to be a first line therapy."

Witt sees Novartis's FTY-720 (fingolimod), the new front-runner, doing about as well as oral cladribine, and for the same reasons. "It has efficacy very similar to cladribine, and the same side-effect profile," she says. "Just a little risky, so it won't be first line." But given the advance in convenience offered by an oral drug, she expects both drugs to reach blockbuster status by 2015.

Biogen Idec's oral candidate, BG-12, is expected to conclude its main Phase III trials in mid -2010, although an extension trial, will assess the drug's safety and efficacy over two years. Teva and Sanofi-Aventis also have promising oral MS compounds in early Phase III.

In the short term, look for injectibles, perhaps more convenient ones, to dominate the market. But in the long run, effective oral therapies are on the way. The next challenge will be differentiating among the new crop and determining which treatments work best for which patients, given how disparate their range of symptoms can be.


Two kinder, gentler oral drugs for a fierce virus

Sometimes being first to market is not only the best thing but the only thing.

Two new protease inhibitors, telaprevir and boceprevir, are competing to be the first compound added to the current standard of care—a cocktail of pegylated interferon and ribavirin—in order to reach the more than half of all patients with hepatitis C (HCV) who do not respond.

The stakes are higher than usual for drugmakers in a race to approval because the rate of incidence of new cases of HCV in the US has dropped sharply over the past decade due to public education and needle exchanges, according to the CDC. If current nonresponders are cured, the patient pool is expected to remain small. "Whoever you have right now, you have to treat," says Alexandra Makarova, an analyst at Decision Resources. "But then you will not have the influx of extra new patients. It's so key to get there first." ThinkEquity LLC analyst Jason Kolbert estimates the market for hepatitis C treatments at about $2.5 billion a year and—oddly, given the projected decline in patients—estimates that it will quadruple over the next decade.

These protease inhibitors will be the first oral, small molecules to show an effect on HCV. The two have similar but not identical mechanisms of action—they are based on different peptide chains but attack the same protease enzyme—and are expected to launch in 2012, according to the WoltersKluwer. Telaprevir is about six to eight months in the lead.

Further back in the pipeline other protease inhibitors are percolating, including TMC435 from Johnson & Johnson, SCH900518 from Schering-Plough (now Merck), and MK7009 from Merck, but the firms may decide to pull the plug if the market diminishes.

Another experimental class of HCV drugs, polymerase inhibitors, may be at least as efficacious as the protease inhibitors and have fewer side effects. They include R-7128 from Roche/Pharmasset and filibuvir from Pfizer. The new compounds also promise dosing advantages, a shorter course of therapy, and, therefore, greater patient compliance. But the firms may choose to pull the plug on the drugs if too few patients remain in the pool to reap profits. "These are better drugs," says Makarova. "But they're just too late."


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