Therapeutic antibodies realise commercial potential

According to a new report the therapeutic antibody market is expected to treble in size by 2010 as significant leaps forward coupled with safer and more effective humanised and fully human antibodies are pouring onto the market fulfilling their long-awaited commercial promise.

Market analyst firm Datamonitor has commented in its latest report of the significant growth achieved in this market during 2004. The mAbs market achieved global sales increasing by 48 per cent to pass the $10 billion (€7.8 billion) mark, which builds on the momentum achieved in previous years.

The mAbs industry has worked extremely hard in recent years to overcome numerous setbacks and dispel concerns over whether antibodies would ever emerge as a practical therapeutic option. From chimeric antibodies (50 per cent mouse-derived structure), through humanised (5-10 per cent mouse-derived) and finally fully human antibodies, the mouse-derived content of antibody candidates has gradually been reduced to minimise immunogenic responses and improve side-effect profiles.

Chimeric antibodies have grown to dominate the mAbs market with 60.2 per cent of sales in 2004, according to Datamonitor healthcare analyst David Evans.

"Key products in this category include Roche/Genentech's Rituxan/MabThera (rituximab) and Johnson & Johnson's Remicade (infliximab). Now, more recently-launched humanised antibodies, including Roche/Genentech's Avastin (bevacizumab) and Herceptin (trastuzumab), MedImmune's Synagis (palivizumab) and Bristol-Myers Squibb's Erbitux (cetuximab), are also starting to make a real commercial impact, along with the first fully human antibody, Abbott's Humira (adalimumab)."

"Together, these have driven exceptional mAbs market sales growth of 48 per cent from less than $7 billion in 2003 to over $10 billion in 2004. In the present environment of decreasing returns on pharmaceutical R&D, these kinds of statistics are making the whole pharmaceutical industry sit up and take notice," he added.

Humanised and fully human therapies are powering a new wave of innovative therapies and rapid market expansion. "Datamonitor forecasts growth for the total mAbs market between 2004 and 2010 at an annual rate of almost 20 per cent, far outstripping the pharmaceutical industry as a whole, while the number of marketed antibodies is expected to more than double," according to Datamonitor healthcare analyst Romita Das.

The wave of fully human antibodies is now flooding the pipelines of not only biotech players, but also big pharma. The major pharmaceutical players such as Johnson & Johnson, Roche, Abbott, Lilly, Schering-Plough and Bristol-Myers Squibb have long had a leading role in the sales and marketing of antibodies, but for the most part, have not historically invested heavily in antibody R&D,

Evans said: "Big pharma is finally moving further upstream and getting involved in early-stage product development. This kind of investment by industry leaders will add the financial muscle and experience needed to fully exploit the exciting potential of antibodies."

These wide-reaching collaborations have dramatically changed the whole outlook of the antibody sector, both for big pharma and for the mAb developers. Antibody companies now have the choice either to go it alone or take on the higher risks and potential rewards of drug development, or to take a more measured, risk-averse approach and rely on a pharmaceutical partner's experience and financial backing to grow their company more gradually.

Several recent deals have highlighted the attractiveness of emerging players, and specifically fully human antibody developers, to the pharmaceutical industry. As well as Roche's broad alliance with Antisoma, in November 2004 AstraZeneca signed a five-year antibody R&D agreement with CAT, following up its 2003 alliance with Abgenix to develop anti-cancer mAbs. Pfizer has also been quick to invest in this emerging area, entering long-term strategic alliances with antibody leader Medarex, and with MorphoSys.

"Either way, antibody developers are now in high demand as partnership or acquisition targets for big pharma looking to snap up the most promising pipelines and technologies-with UCB's recent acquisition of Celltech a recent example, while Roche's purchase of Genentech in 1990 must surely rank as one of the most astute acquisitions of all time. The antibody market sector is maturing from being a technological innovation with much to prove, to a well-regarded, established and profitable arm of the mainstream pharmaceutical industry," Evans said.

The report expected the antibody industry to have a promising future. Beyond fully human antibodies, conjugated antibodies (linked to small molecule drugs, toxins, or radioactive payloads) have shown strong theoretical potential, particularly in the treatment of cancers.

However, practical considerations such as cost and complexity of treatment have so far seriously limited their use, says Das. "Ongoing development projects may well overcome these problems, and allow conjugated antibodies to fulfil their promise," she added.

Antibody fragments could further expand the mAbs market, being more suitable for treating certain diseases; for example by allowing better penetration of tumour tissues. UCB's CDP 870 and Genentech's Lucentis (ranibizumab) are two key antibody fragment candidates with a strong outlook. Fusion proteins, consisting of antibodies linked to protein therapeutics, are an extension of antibody technology that are also turning a healthy profit, as evidenced by the success of Amgen's Enbrel (etanercept).

"Another key factor that is set to extend the success of antibody products is the lack of generic competition defining the end of their commercial lifecycles," Das says.

"Because no regulatory framework exists for 'biosimilar' antibodies and none is expected for several years, the first antibody products will benefit from a longer lifetime and only gradual sales erosion by new branded competitors," she added.

Of course, risks to individual products remain, as shown by the hugely disappointing suspension of Biogen Idec/Elan's multiple sclerosis antibody, Tysabri (natalizumab), as a result of safety concerns.

Nevertheless, these pipeline setbacks will be outweighed by the expected success of new antibodies with huge blockbuster growth potential, such as Humira, Avastin, Erbitux and CDP 870.

"With the mAbs market set to triple in size to $30 billion by 2010, the antibodies industry has never looked healthier," Evans commented.