Peter Keeling of Diaceutics considers the reasons why treatments for rheumatoid arthritis will likely transform to a predominantly personalized medicine market faster than we think.
Rheumatoid arthritis (RA) will likely transform to a predominantly personalized medicine market faster than we think. Why is this? There are perhaps several ‘perfect storm’ reasons why RA in particular lends itself to becoming one of the first personalized medicine frontiers outside of oncology. First is the unmet clinical need. The Centers for Disease Control and Prevention estimates that in the US approximately 1.5 million people have RA at various stages of disease1. The lifetime cost of disease was estimated in 1998 by Gabriel et al.2 (i.e., 25 years following a diagnosis of RA) to be $61,000 to $122,000 (US 1995 dollars), a number that is bound to have doubled in the subsequent years .
A second reason is that although early diagnosis is challenging because the symptoms of early RA can be non-specific (e.g., malaise, fatigue, weakness, muscle soreness, low-grade fever, weight loss), and may actually be symptoms of other conditions, doctors believe there are compelling reasons to treat rheumatoid arthritis before the onset of irreparable joint damage (http://www.arthritistoday.org/conditions/rheumatoid-arthritis/ra-treatment/how-to-treat-ra.php). New studies are now showing that taking action quickly may even put the disease into remission3. Ergo, effective treatment and efficient diagnosis are natural bedfellows as the next clinical frontier.
A third reason is likely also to be the mounting wasted costs being encountered by payers who are looking at the incremental cost of a QALY for patients treated with biologics of $50,0004. This sticker price is partly because this cost includes between 29 to 54 per cent of patients treated with biologics targeting TNF who do not adequately respond to the drugs. Furthermore, this lack of response may take up to six months to discover, further delaying potential treatment alternatives4.
A fourth reason is that, like so many common diseases, there is an increasing series of improved diagnostic options near or on market. Recent announcements by Crescendo (http://www.bizjournals.com/sanfrancisco/blog/biotech/2012/08/crescendo-rheumatoid-arthritis-vectra.html) and GSD (http://us.generation-nt.com/upgrade-autoimmune-diagnostic-testing-using-multiplex-technology-press-3688882.html) symbolize the marked increase in diagnostic investment in RA and other inflammatory conditions.
So, on the surface we should expect a market-based convergence of factors to propel RA onto the personalized medicine red carpet. But wait…
Nothing cited above is new news, nor is the potential financial benefits to pharma of the early treatment market opportunity. Diaceutics itself completed a financial assessment of the investment benefits of treatment targeting for Roche as far back as 20065. So why has a personalized medicine market not yet occurred in RA, and what will change this?
Our analysis of multiple therapy areas suggests that the presence of ripe conditions (as cited above) for personalizing a therapy/treatment area alone is never enough to propel a market towards personalization. Indeed, if this were so we would have already witnessed targeted treatments predominating in sexually transmitted diseases like herpes or chlamydia, or multiple sclerosis or Alzheimer’s. Instead we observe that the single biggest factor which tips a market towards personalized medicine is in fact the competitive reshaping of a treatment pathway by one company seeking a first mover advantage.
So the next obvious question I hear you ask is, who will be first in RA? In fact, at Diaceutics we believe that accolade already goes to Roche with the work they have done via the REFLEX study and others to competitively reposition Rituxan/MabThera in Anti CCP and Rheumatoid Factor positive patients6. Whilst submission of this data has not (yet) led to a revised FDA label moving Rituxan from a third line treatment in the US, Rituxan (or MabThera as it is called in Europe) has benefited from enhanced efficacy claims in seropositive patients.
It is our view that Roche’s simple use of two existing RA-related biomarkers to enhance Rituxan came late (perhaps too late) in the lifecycle of Rituxan to make a profound competitive statement. Our research shows the biomarker/rituxan-related publications pre 2006 and post 2006 indicate a surge of biomarker-related publications only (and Roche-sponsored research) from 2006 onwards. However, we do believe it represents a first move in what promises to be a rapid (in drug development terms) conversion towards a personalized medicine predominant marketplace. Anecdotally, at the most recent EULAR meeting in Berlin there was standing room only in each of the biomarker sessions, with our representative there counting some 250 to 300 people in each. Only a few years ago you would be lucky to have 25 to 30 attendees to such sessions.
So there you have our bottom line with regards to personalized medicine markets. In short, that whilst the clinical, financial and industrial incentives may be aligned in a treatment area—something we assessed in depth during our recent Diaceutics Convergence Summit in Washington DC—in fact it is good old competition which triggers a personalized medicine market. Herceptin was not only a poster child in oncology, it was in fact a competitive earthquake. Our advice is simple, therefore, read the tea leaves to determine which treatment areas are poised awaiting that first competitive move. Surely those pharma companies who have cited that 70 to 90 per cent of their future pipelines will be biomarker-enabled are likely looking at the bottom of the cup right now.
(2) Gabriel SE, Crowson CS, Luthra HS, Wagner JL, O’Fallon WM. Modeling the lifetime costs of rheumatoid arthritis. JRheumatol. 1999; 26(6):1269-74
(4) Olsen NJ, Stein CM: New drugs for Rheumatoid Arthritis. New Engl.J.Med 350, 2167-2179 (2007)