Pfizer got the vote of confidence it sought for rheumatoid arthritis pill tofacitinib (Xeljanz) – backing from FDA expert panellists for use on an even footing with blockbuster biologicals such as Humira and Enbrel.
Lingering safety worries are likely to line it up behind antibodies, the result of law or clinical practice, as long-term data accumulates – a limited number of patients have been exposed to two years or more of dosing to this chronic disease drug (Event - Pfizer's RA pill facing crucial panel verdict, May 4, 2012). However there looks to be little doubt the New York pharma giant should receive approval for the future blockbuster by late summer, paving the way for one of the most anticipated launches of the year.
All drugs have risks, and as long as RA therapies rely on suppressing dysfunctional immune system function to relieve disease symptoms, cases of infection and cancer will be seen – Humira and Enbrel, the two biggest sellers in the space, have black box warnings about infections, with Enbrel carrying a warning for lymphomas.
So it is with tofacitinib, which has both associated with it, with the FDA concerned most with lymphomas – 1.4 cases per 100 patient years in patients taking 10mg twice a day, 1 per 100 patient years at a 5mg twice-daily dosage, according to the regulator’s analysis.
Whilst its efficacy was never in doubt the relative shortness of patient exposure when compared to the antibodies on the market has inspired some caution from specialists wanting more safety data (ACR - Pfizer's tofacitinib heads to FDA as role in RA debated, November 8, 2011).
Pfizer wants a label that would allow tofacitinib to be prescribed after failure on one or more disease-modifying anti-rheumatic drugs (DMARD), which in practice means methotrexate – the same position as antibodies in the cascade of treatments. The panel’s vote was 8-2 in support of that position, with the two negative votes coming from experts wanting to restrict use to patients who stop responding to a biological drug. In addition, analysts noted a sentiment in favour of the lower 5mg dosage.
Given the risk and uncertainty, it may be the case that the FDA listens to those negative votes. Should this come to pass, it is not likely to be a huge disappointment to investors, as analysts are largely building forecasts on the assumption that biological non-responders will be the main use until further safety data can be analysed.
Tofacitinib is forecast to sell $49m in the few months following launch this year, increasing to $2.14 bn worldwide in 2018 for Pfizer, with Takeda earning $137m from its co-promotion in Japan, according to consensus data from EvaluatePharma.
A broad label could potentially cause those forecasts to increase modestly. Downward revisions could result from a delay in the approval date or a more restrictive label than analysts are anticipating, such as a requirement that patients fail on two or more biologicals before receiving tofacitinib.
The positive vote also should increase optimism that the janus kinase (JAK) inhibitor class will be able to carve a niche in the RA space as it has begun to in cancer. Tofacitinib would be the second JAK inhibitor to reach the market, following approval of Jakafi for myelofibrosis late last year.
This should build confidence for the clinical programmes of JAK pioneer Incyte, the developer of Jakafi which has partnered its RA JAK1/2 inhibitor, now known as LY3009104, with Eli Lilly. Galapagos, which has partnered its candidate GLPG0634 with Abbott Laboratories, will also take comfort from this success (Galapagos delivers in style with fat Abbott deal, February 29, 2012).
Analysts from UBS noted that the advisory committee’s discussion considered the lymphoma risk to be tofacitinib-specific, which provides an opportunity for other JAKs to differentiate themselves on safety. Incyte shares were up 1% at $22.70 in early trade today, close to the 11-year high they reached last week, whilst Galapagos was 4% higher to €10.75 in late afternoon trading in Europe.
If tofacitinib gets approval in August as is now widely expected, it will have considerable first-mover advantage over those two phase II compounds – if current forecasts are met it will be closing in on blockbuster sales before those can be launched. Further confirmation of safety data would make the first JAK inhibitor in RA a difficult rival.