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Biologics Have the Inside Track on IBD Treatment
Posted on 2007-02-27 13:40:00
Inflammatory bowel disease (IBD) affects approximately 1.8 million people in Europe and the U.S, according to Datamonitor, a UK-based research firm. Ulcerative colitis and Crohn’s disease are the primary constituents of IBD, and are caused by a complex interaction of environmental, genetic and immunoregulatory factors. Although rarely fatal, IBD can severely limit the sufferers quality of life. While the incidence of ulcerative colitis is flat-lining, emerging studies show that Crohn’s disease appears to be on the increase.
A new report by Datamonitor forecasts a growing market and the launch of six major brands in IBD indications in as many years. However, few appear to offer especially novel mechanisms of action.
Higher rates of IBD are generally seen in northern, industrialized countries and a growing body of data implicates a dysfunctional mucosal immune response to commensal bacteria in the development of IBD, especially Crohn’s disease. Possible triggers include a chronic inflammatory response precipitated by infection with a particular pathogen or virus or a defective mucosal barrier. Crohn’s disease most commonly affects the lower part of the small intestine but can actually affect any area of the gastrointestinal (GI) tract from the mouth to the anus, while ulcerative colitis more commonly affects the colon and rectum, says Datamonitor senior analyst Clare Churchill.
“About half of the people diagnosed with ulcerative colitis have mild symptoms, while others suffer frequent fevers, bloody diarrhea, nausea, and severe abdominal cramps.”
The terms ulcerative colitis and Crohn’s disease were created many years before the exact nature of IBD was understood—something that cannot be claimed even now. Recent discussion about the use of these terms in describing IBD has led to a theory that IBD could be better classified, with more than two classes, enabling a greater understanding of the variance and overlap found in this disease.
The classification of the disease is important as patient segmentation is expected to be key in the future of IBD treatment, Churchill says. “The terms ulcerative colitis and Crohn’s disease will remain, but any cross-over between the conditions and segmentation within the diseases will dictate treatment procedures.”
The current management of IBD focuses on diet and nutritional therapy for mild disease sufferers and anti-inflammatory and corticosteroid therapies if the disease becomes more severe. A step-up treatment regime would then move to more potent corticosteroids then traditional immunosuppressant therapy followed by, or in combination with, a biologic therapy. Once the treatment has the inflammation under control, lower doses are usually employed to keep the disease in remission. These treatments aim to achieve symptom relief, but increasingly the maintenance of remission and clear mucosal healing are being considered key outcomes.
The last resort is surgery involving removal of diseased sections of the intestine. However, unlike ulcerative colitis, being a systemic disease of the gut Crohn's cannot be "cured" with surgery and the disease can often re-occur. This fact increases the need for pharmacological therapies to treat the more severe Crohn’s disease patients.
In 2005 40% of IBD sales were for biologics, including some off-label use, and the intestinal anti-inflammatories are estimated to create 50% of the total market sales.
Eight years after the launch of Centocor and Schering-Plough’s Remicade (infliximab) in Crohn’s disease the next generation of anti-TNF’s are poised for approval, and are predicted to increase the dollar value of the market significantly. However, this time gap has allowed some novel cytokine therapies to be developed and means the anti-TNF class will soon be under attack. In particular Datamonitor predicts that Elan and Biogen Idec’s resurrected Tysabri (natalizumab) will provide a promising candidate for patients failing anti-TNF. The excitement over these emerging agents is tempered by the potential side-effects, some of which are unique to each class of drug, but Gastroenterologists do not appear overly worried by the 1 in 1000 chance of life-threatening progressive multifocal leukoencephalopathy (PML) with Tysabri.
UCB’s Cimzia (certolizumab) and Humira (adalimumab) target TNF and offer similar product profiles. Datamonitor predicts that both will initially be used after Remicade in the treatment algorithm, until sufficient physician and patient confidence is achieved. The battle between the two will depend on efficacy, convenience and cost, Churchill says. “Datamonitor believe Humira’s efficacy in all patient segments and it’s wealth of safety data, added to the fact that it has already been used off-label could lead it to prevail over Cimzia’s superior dosing regime,” she says.
The launch of these and other new biologic and traditional therapies is expected to significantly change the market over the next two years, increasing the estimated sales attributed to Crohn’s disease to over $2 billion by 2008 in the seven major markets, three quarters of which is accounted for by the biologic therapies.
Positioning in the treatment algorithm is key for the biologics, and after the obvious need for efficacy, competition for all IBD products is focused on delivery method and dosing regimes.
Remicade was approved for moderate to severe ulcerative colitis by the FDA in September 2005, which made it the first biologic therapy approved to treat ulcerative colitis, which as of March 2006 is also true in the EU.
Because surgery can effectively be a cure, and ulcerative colitis patients respond better to 5-ASAs, an existing class of medication, Datamonitor predicts less success for biologics in this indication. However, Shire’s Lialda (known as Mesavance in the EU), approved by the FDA for ulcerative colitis in January 2007, is forecast to have strong uptake, despite merely being a new formulation of the ubiquitous mesalazine molecule.
Lialda’s once daily dosage regime is claimed to be a significant step forward for ulcerative colitis treatment over other oral mesalazine and mesalazine-prodrug formulations, which require three to four times daily dosing and six to 16 pills a day. However, clinical trials do suggest that Lialda twice-daily as the best option for existing 5-ASA patients to switch to, reducing this key advantage over existing therapies and tempering Datamonitor’s predictions.
After the dearth of new therapies in this area for the better part of the last decade, a more competitive market is predicted, something that can only be good news for IBD suffers, Churchill says. “On the surface, the launch of Lialda, Humira and Cimzia appear to be a significant step forward, but the fact is none of these treatments involve particularly novel mechanisms for IBD treatment. Physicians in need of new options must look to more controversial and early phase products.”
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