Multiple Sclerosis: The Advent of the Orals
The $8 billion dollar multiple sclerosis (MS) market is set to double the number of available treatments in the near future,
with a dramatic switch from injectables to oral medications. On the heels of Novartis' first-to-market Gilenya, whose uptake
has exceeded all expectations, Merck KGaA, Teva, Sanofi-Aventis, and Biogen Idec all have MS pills prepping for a date with
the FDA. Developed by MS powerhouse Biogen, BG-12 (dimethyl fumarate) triggers the Nrf2 pathway, defending against oxidative stress that can cause inflammation and injury to
neurons and the CNS myelin, which, in turn, trigger MS symptoms. Phase IIb data also showed that B-12 cut the number of brain
lesions in patients with relapsing-remitting MS by 69 percent compared to placebo.
Two Phase II injectable monoclonal antibodies also evince disease-modifying promise. Roche's ocrelizumab, a monoclonal antibody related to rituximab for rheumatoid arthritis (RA), depletes B cells, which play a role in the autoimmune
destruction caused by MS. In a Phase II study, the high dose of ocrelizumab reduced the number of brain lesions by 96 percent
compared to placebo, the low dose by 89 percent. The relapse rates fell by 80 percent and 73 percent, respectively.
Genzyme's alemtuzumab, already sold as Campath for chronic lymphocytic leukemia, shows exceptional efficacy, reducing the relapse rate of patients
in a Phase II study by 87 percent after five years, compared to the standard of care. The monoclonal antibody targets the
CD52 protein on the surface of certain T cells, B cells, and other lymphocytes, which MS mistakenly turns against neurons
and myelin. Over the ensuing several years, these immune cells grow back—theoretically free of the MS stamp. Should alemtuzumab
win approval, Genzyme (or Sanofi-Aventis, if its hostile takeover succeeds) will face the ethical and PR quandary of pricing
a new drug for MS that is already available as a cancer drug, the quandary being that MS patients need only eight infusions
over four years, about $10,000 at Campath's rate. Rival MS treatments cost $30,000 or more.
Lupus: How Big will Benlysta Become?
The headline news in autoimmune disease R&D is the launch of the first new treatment for lupus in half a century. Current
treatment is limited to steroids and other immunosuppressants, whose side effects can be worse than the symptoms of the disease.
Says Decision Resources analyst Michael Latwis: "Lupus has been a very challenging therapeutic area for decades, in part because
its symptoms vary so widely that clinical efficacy is exceedingly hard to establish." Yet Human Genome Sciences/GSK's Benlysta (belimumab) was approved by an FDA advisory committee in November—to the cheers of many patients who had testified to their
need of the novel (if less than overwhelmingly efficacious) therapy.
A monoclonal antibody delivered by monthly infusions, Benlysta targets an immune protein called B lymphocyte stimulator (BLyS)
that causes the hyperactivity of tissue-destroying B cells. BLyS was discovered by Human Genome Sciences in its vast trove
of human genes in the glory days of the genomics revolution.
Despite inconsistent results in Phase III trials, the FDA is almost certain to wave Benlysta through to market. "It may only
help a small number of patients," says Wolters Kluwer's Ben Weintraub. "Once again, marginal efficacy weighed against major
unmet medical needs is likely to carry the day."
Rheumatoid Arthritis: JAKing Down Inflammation
In the race to market the first oral drug to compete with high-priced injectables for rheumatoid arthritis (RA), Pfizer's
tasocitinib has the home-stretch lead over Rigel, Vertex, and Incyte. All four contenders are Janus-associated kinase (JAK) inhibitors,
a new class of molecules with anti-inflammatory activity that puts the brakes on RA's joint destruction. In a 600-patient
Phase III trial, Pfizer's twice-daily anti-JAK pill reached two of three of its goals, reducing symptoms and increasing functionality,
but failing to best placebo in number of remissions. Three out of four patients saw a decrease in pain and inflammation. However,
the drug raised the levels of both good and bad cholesterol, a regulatory red flag, especially for drugs used long term by
elderly patients. As a first-to-market RA pill, tasocitinib could garner $2 billion annually in sales, says Sanford C. Bernstein
& Co's Tim Anderson.