Monoclonal Antibodies

TOP CONTRIBUTORS

Jay Tan

The monoclonal antibody (mAb) market has grown rapidly in recent years, reaching sales of $14bn in 2005, an increase of 36.5% from 2004 sales of $10.3bn. Köhler and Milstein developed the hybridoma method of murine antibody production in 1975, which allowed the production of the first mAb to market; Johnson & Johnson’s Orthoclone OKT3 (muromonab) in 1986. The mAb market is highly innovative and a key trend has been the move from murine to humanized and fully human antibodies. As technology has progressed these humanized mAbs have prevented immune responses (HAMA), thus having a larger market potential. The traditional therapy areas in the mAb market are oncology and autoimmune and inflammatory disorders (AIID), however this is forecast to change with the emergence of other therapy areas including infectious disease and ophthalmology. The clear leader in the mAb market is Genentech with 5 marketed drugs, with sales totaling $4,116.4m in 2005.

The leading mAbs are Remicade and Rituxan, with sales of $3.5bn and $3.3bn, respectively in 2005. However, sales growth of Rituxan is expected to be limited due to a lack of studies investigating new indications. The rapid increase in the number of mAb pipeline drugs is a result of innovation in the market, which has allowed companies to develop fully human drugs with reduced immunogenicity and mAb fragments that are cheaper to produce and have a high efficacy. Despite the high growth in the mAb market, there remain many issues resisting the market, including mAbs being withdrawn from the market, publicized side-effects, pricing and reimbursement issues and competition from small molecule drugs. Oncology is the largest therapy area within the mAb market, with 8 marketed products. This therapy area is set to increase with numerous early and late stage products in development. Key oncology pipeline products include Virexx’s OvaRex, Abgenix/Amgen’s ABX-EGF and Medarex/Bristol-Myers Squibb’s MDX-010 and MDX-1379. AIID is the second largest therapy area in the mAb market, with 7 marketed drugs. Many of the marketed AIID drugs are indicated for the same disease, and consequently there is a high level of competition between drugs. For example the leading mAb Remicade, with sales of over $3.4bn in 2005, is indicated for Rheumatoid Arthritis (RA), as is Humira. Synagis is the only current anti-infective mAb on the market. However, due to a large number of early and late stage pipeline products, this therapy area is expected to expand in the next 5 years. Key pipeline products include Numax and Aurograb.

Key challenges facing the mAb market include the imminent bioequivalent regulations, which once in place are forecast to heavily impact sales of currently marketed drugs. The negative publicity from clinical trials or other reported adverse side effect will also challenge sales due to physicians switching to alternative small molecule therapies.

The monoclonal antibody (mAb) market has grown rapidly since the launch of the first drug, Johnson & Johnson’s Orthoclone OKT3, in 1986. The global mAb market reached $14bn in 2005, an increase of 36.5% from 2004 sales of $10.3bn. The mAb market is outperforming the total global pharmaceutical market, which grew 7% in 2005.

Biogeneric regulations To date there are no biogeneric regulations in place in the US, EU or Japan. Sandoz’s Omnitrope (Somatropin) was the first generic biologic drug approved by the FDA on the 30th of May 2006 and was filed under an NDA (new drug application). However, the FDA has stated that this is not a biogeneric, and thus this approval has not paved the way for future generic versions of biologics. Biogeneric regulations are not expected to be straight forward, as it is impossible to create an identical generic biological, due to the nature of protein folding and the specific method of mammalian cell culture and purification procedures used by the originator. However, a bioequivalent or biosimilar drug can be produced, which demonstrates the same efficacy and levels in the blood. Once bioequivalent regulations are established generic versions of mAbs are expected to impact heavily on branded sales. One factor that could resist this decline in product price is the difficulty in obtaining biologic generic approval, as the manufacturing facilities need to be approved along with the product, and the manufacturing process is more expensive than small compound production, limiting the number of players and thus reducing competition.