Competition is heating up as science improves our understanding of the disease. A number of drugs based on new mechanisms of action with potential advantages over existing TNF inhibitors, including longer half-lives and reduced dosing schedules, are entering the market. Biogen Idec, Genentech and Roche's MabThera/Rituxan (rituximab) and Bristol-Myers Squibb's Orencia (abatacept) are the latest examples, but more are about to come.
Patients need more options
The reason why the market is growing fast and so many companies are interested in this therapy class is simple: about 35% of RA patients are untreated and only around 13% receive a biologic drug, according to IMS. In addition, from all patients treated with anti-TNFs, about one-third do not respond to, or have an unsustainable response to, the drugs. “Patients have not had a better treatment than now”, says Ali Jawad, consultant rheumatologist at the Royal London Hospital, “but we are still in need of more agents to take the treatment really further.”
RA is a big and promising market. Approximately 1% of the global population is thought to be affected by the disorder, an autoimmune disease that usually causes progressive symmetrical inflammation and damage of the joints by destroying the articular surfaces covering the bones. One in three patients is likely to be disabled within 20 years. Onset often occurs between the ages of 25 and 50 years and is three times more prevalent in women than in men.
Three main products – for now…
Methotrexate, an old cancer drug, is the most popular therapy and has been used also in combination with the three anti-TNFs currently on the market: Johnson & Johnson/Schering-Plough's Remicade (infliximab), Amgen/Wyeth's Enbrel (etanercept) and Abbott's Humira (adalimumab), which was co-developed by Cambridge Antibody Technology of the UK – about to be acquired by AstraZeneca as it seeks to strengthen its biologics portfolio. The only other significant biological RA therapy is Amgen’s Kineret (anakinra), but this has a narrower label and modest sales. The major branded small molecule for RA is sanofi-aventis’ immunomodulator Arava (leflunomide).
Sales of leading RA therapies*
12 months to March 2006
*Note: sales generated by all approved indications, including e.g. RA, Crohn’s disease, psoriasis etc.
Source: IMS MIDAS Quantum, MAT (moving annual total) to end March 2006
Industry analysts believe anti-TNFs and novel biological agents will drive the RA market to more than $10 billion by 2015, as physicians become more familiar with the new drugs – seeing their long-term efficiency and side-effect profile – and thus more willing to use biologicals in a greater number of patients. Humira and Enbrel are believed to be the biggest benefactors of this trend because they are self-administered, which gives them an edge over Remicade – an intravenous product that has to be administered in a clinic. Both drugs are projected to exceed $3 billion in sales by 2010, while Remicade is expected to slow down and maybe decrease a little.
The lucrative prospective has encouraged many companies to jump on the anti-TNF bandwagon. UCB, for example, is developing Cimzia (certolizumab pegol), another monoclonal antibody directed against TNF-alpha; it was the major reason for UCB’s £1.5 billion takeover of the leading UK biotech Celltech in mid-2004. Although it has been filed first as a treatment for Crohn's disease, Cimzia is also in Phase III trials for RA and is expected to be submitted for approval in this indication during 2007. Centocor, the J&J subsidiary responsible for developing Remicade, also has another anti-TNF in the pipeline: the follow-on golimumab is in Phase II trials for RA and has showed good clinical results so far.
Roche takes a different approach
Other companies, however, are looking at different ways of treating the disease. “RA is such a dissatisfied area of medicine and doctors are regularly looking for new ways of treating their patients – I think the stage is set,” says Bill Burns, Pharma CEO at Roche (an expanded interview with Burns will soon be available in the IMS Company Profile on Roche). In 2006, the Swiss giant entered this market by launching its best-seller MabThera/Rituxan, originally developed (by Biogen Idec and Roche’s US affiliate Genentech) for the haematological malignancy non-Hodgkin’s lymphoma, for the treatment of RA patients who failed anti-TNF therapy.
Hoping to get a reasonable portion of this lucrative market, the company developed another MAb, Actemra (tocilizumab). Originated by Chugai, Roche's Japanese subsidiary, Actemra is awaiting approval in Japan for RA and is in Phase III trials elsewhere. Roche also has at least four other projects targeting RA. “There are three anti-TNFs that are all trying to attack the same target. So why wouldn't you use something with a totally different mechanism of action?” asks Burns, explaining that the market is competitive but that 70-80% of revenues are coming from biological drugs.
The same line of thought led BMS in early 2006 to launch Orencia, a T-cell co-stimulation modulator, which has been approved more broadly than MabThera/Rituxan, including for use in patients who failed other disease-modifying anti-rheumatic drugs (DMARDs), like methotrexate. Both MabThera/Rituxan in RA and Orencia are predicted to reach blockbuster sales levels, despite competing with each other.
“These are very promising drugs and will help those patients who do not respond to current treatment. They will optimize treatment, but I don't believe they will substitute anti-TNF drugs,” commented rheumatologist Ali Jawad. What is known for sure is that the treatment of RA is changing, and this is good news for patients.
This article was written by Johanna Kleine, Editor of IMS Company Profiles. Much of the information is available on IMS Knowledge Link, which integrates detailed data from a number of publications covering sales, R&D, news, patents and strategic issues on a single website. The extensive coverage includes more than 2,000 pharma and biotech companies, 300 therapy areas and 36 countries. For more information, please visit imsknowledgelink.com or contact Stephanie Earle via e-mail or call +44 207 393 5757.