Biologic therapies have deep penetration into the rheumatoid arthritis (RA) market, but many patients with the disease are not being treated.
“A significant number of patients do not think their RA is that serious,” says James Salanty, divisional VP and GM for rheumatology, in the pharmaceutical products division of Abbott, maker of the injectable RA drug Humira. Abbott estimates half of RA patients are not being treated by a rheumatologist for their disease.
Resistance to injections is one of three main obstacles to patients getting on a biologic, a Credit Suisse survey found. Safety concerns and cost are the other two. In February, Abbott launched a disease awareness campaign to help consumers understand the role of treatment in preventing joint damage, an RA hallmark and one which the company says can occur no matter how much, or how little, pain patients feel. Salanty says a branded campaign will follow.
Could a drug given by mouth have appeal for the untreated, as well as for those already on therapy who want a more convenient, or cheaper, alternative? Perhaps most at risk from orals are the five leading TNF inhibitors: Amgen/Pfizer's Enbrel, Johnson & Johnson/Merck's Remicade and Simponi, Abbott's Humira and UCB's Cimzia. The stakes are also high for the back-up treatments Orencia (Bristol-Myers Squibb), Actemra and Rituxan (Genentech), and Kineret (Biovitrium).
Many of these injectable biologics have expanded indications into disease states that are autoimmune-related—ulcerative colitis, Crohn's disease, psoriatic arthritis, psoriasis and ankylosing spondylitis. Across these lines of therapy, the currently approved RA drugs generate more than $12 billion in US sales, according to data from Wolters Kluwer Pharma Solutions (see chart, right).
The furthest along of the orals is Pfizer's JAK-3 inhibitor tofacitinib. So far, phase III data make it clear this is an effective drug. If approved, will it be used before existing drugs or, due to side effects, will it be used after?
Credit Suisse, which surveyed 50 high-prescribing rheumatologists, found that, if tofacitinib were priced close to biologics and showed radiographic benefits, respondents expected to use it in about 25% of new RA patients, rising to 35% if discounted.
Tofacitinib data have been mixed. While the agent met its primary endpoint in some phase III trials, Pfizer reported four patient deaths in the treatment arm of another. Still, data support tofacitinib “competing as an oral therapy in a largely injectable world,” much like Novartis' oral multiple sclerosis drug Gilenya, writes Sanford C. Bernstein analyst Tim Anderson in an investor note.
A regulatory filing for tofacitinib is likely later this year, and there is always the possibility of rejection. If approved, it's difficult to say how it will do against the injections until head-to-head trials—including one testing it against Humira—are fully read out later this year. Anderson models $1.4 billion in worldwide annual sales for tofacitinib in 2015, and that only includes the RA setting.
“We only [forecast] a 50% chance [tofacitinib] will get approved at all, and if it does, its safety profile leans toward use in TNF-inhibitor refractory patients. So that gives it a sales potential of under a billion dollars,” counters Ben Weintraub, PhD, director of research, Wolters Kluwer inThought.
Also in step with Pfizer's play for the oral market are Rigel and AstraZeneca, whose Syk inhibitor fostamatinib (R788) is in phase III.
The next installment of MM&M's Therapeutic Focus will be August's look at infectious disease products