A new era of targeted oral therapies?
Rheumatoid arthritis (RA) treatment options have expanded from conventional oral therapies like methotrexate, through the era of targeted injectable biologics and into a new dawn of targeted oral treatment.
Xeljanz, Pfizer’s first-in-class JAK3 inhibitor (tofacitinib), was launched in the US in 2012 – the first oral therapy approved for RA in over a decade. The drug has approval for second-line use. With similar efficacy to the injectable TNF-inhibitors, this means it’s well positioned to compete against them from a clinical and convenience perspective. But as with other disease-modifying antirheumatic drugs (DMARDs), Xeljanz is not without potentially serious side effects which will require close scrutiny and will leave many rheumatologists reticent to become early adopters. The high price of the treatment is also dampening enthusiasm. It is reportedly priced similarly to Abbott’s Humira, one of the top selling TNF-inhibitor monoclonal antibodies (mAbs). Japanese and European approval is currently being sought.
Other oral therapies are also in the pipeline, such as Lilly/Incyte’s baricitinib, AstraZeneca’s fostamatinib and Vertex’s VX-509.
Biosimilars on the horizon.
At the same time, the green light could soon be given to mAb biosimilars for the treatment of RA. Recently the EMA issued guidance on the development of biosimilar mAbs, which are larger and more complex than the biosimilars that are currently available in Europe (such as human growth hormone and erythropoietin). FDA draft guidelines outlining the regulatory pathway for biosimilars have finally been released too.
As the first biological therapies indicated for RA edge closer to patent expiry, it is not surprising to find that there is considerable activity in the development of these cheaper follow-on versions. Korean biopharmaceutical company Celltrion has been the first to submit an application. It is the first regulatory application for a biosimilar mAb – for any indication – in Europe. Its version of infliximab (Remicade) has been through extensive clinical trials and the outcome of this submission is imminent. The product has already been approved in Korea. Celltrion and several other manufacturers are developing other biosimilars for RA, including Boehringer Ingelheim’s version of rituximab (MabThera) which entered phase III development in 2012, and Fujifilm Kyowa Kirin Biologics biosimilar adalimumab (Humira).
Confidence in biosimilars is likely to be determined not only by stringent regulatory approval processes, but through real world experience with them. Rheumatolgists are only too aware that these agents are ‘similar’ and not ‘the same’ as the originals, since the complex manufacturing processes cannot be copied identically. No-one is expecting erosion of the biologic brands’ patient shares to anything like the extent seen with synthetic small molecule generic competition. However, safe and effective alternatives, at a price discount, will be tempting in this high cost market, and could help push the biologics more into first line therapy.
Will these diametrically opposite new developments fundamentally alter treatment in RA then? Will the treatment paradigm come full circle back to oral therapy – with convenience outweighing high pricing and payer restrictions? Or will we see the trend towards earlier, more aggressive treatment intensified with the availability of cheaper biosimilars?
What we do know is that in the treatment of chronic, severe disorders like RA, safety and efficacy will always remain top priority. These additional treatment options will be welcomed since there is high unmet need. However, the market will have to balance the views of rheumatologists wanting to slowly gain experience and trust of newcomers – whatever their shape, size and mode of administration – with the increasing needs of payers to manage costs and improve patient access to effective medicines.
Since potentially similar scenarios will begin to play out in other fields, notably oncology, the RA market will certainly be an interesting one to watch and learn from over the coming years.
Update July 2013
- Xeljanz is now approved in Japan and in other strategic markets, although approval in Europe has been initially rejected. Pfizer has requested a re-examination by the European Medicines Agency.
- AZ have returned rights to fostamatinib back to Rigel after disappointing PIII results.
- Celltrion’s infliximab biosimilar has been approved in Europe. It will be marketed as Remsina by Celltrion, and Inflectra by Hospira.
Want to Dig Deeper?
A New Chapter in Rheumatoid Arthritis Therapeutics. R Van Vollenhoven. Medscape Rheumatology. Feb 2013.
The role of biosimilars in the treatment of rheumatic diseases. T. Dorner et al. Ann Rheum Dis 72. p322–328. 2013.
Biosimilar monoclonal antibodies on the horizon in Europe. GaBI online. Jan 2013.
U.S. Prepares Groundwork For Biosimilar Approvals. Clinical Oncology News 7. May 2012.