Rise of biologicals – Editorial – Express Pharma Pulse

Rise of biologicals

Antibodies have a much higher success rate due to recent advances in target selection and the development of recombinant antibody technology, says Dr Krishan Maggon in the concluding part of the article

The risk associated with the development of human antibodies and biologicals is typically lower than that with small molecule therapeutics where the probability of a product going into clinical development and its chance of making it to approval can be less than eight per cent. This lower risk is a function of their superior safety profile and target specificity.

Antibodies have a much higher success rate, particularly when the therapeutic is a chimeric or humanised antibody. Much of this success is due to recent advances in target selection and in the development of recombinant antibody technology. Target selection was a problem in the past because the number of known targets was limited; however, with the advent of the genomic/proteomic revolution, the number of available targets has exploded.

Other important new developments include techniques for converting murine monoclonal antibodies to mouse-human chimeric antibodies, for humanising the antibodies, and producing human antibodies using transgenic mice. These approaches minimise or eliminate the immune response problem associated with the earlier murine antibodies.

Anti-infective exodus

In the past four years several large pharmaceutical companies in fact either eliminated or greatly curtailed their anti-infective research activities during prioritisation of their R&D efforts. Such names include Aventis, Bristol Myers Squibb, Eli Lilly, Roche, GlaxoSmithKline, Proctor & Gamble and Wyeth, and it is fair to assume that many others will follow suit.

The R&D restructuring and downsizing has resulted in elimination of thousands of jobs and has affected mainly persons over 50 years old. The elderly patients are the major consumers of medicines and health care services and strongly resent paying high out-of-pocket prices for the drugs. The reasons for pharmaceutical companies leaving the vaccine market claiming unprofitability, and low investment in vaccine companies.

Vaccines are unattractive targets for industry, underappreciated from the public health perspective, under funded by basic research organisations, and treated with suspicion by the public. Vaccine manufacturers are running scared and hesitate to launch a product with annual sales in the tens of millions of dollars if a punitive damages settlement in the billions of dollars is an ever-present threat.

Public-private partnerships

Public-private partnerships linking together government, non-government organisations, industry, and academic partners may accelerate the discovery and/or development of vaccines and drugs. The Foundation for the National Institutes of Health established by the United States Congress identifies and develops opportunities for innovative public-private partnerships involving industry, academia, and the philanthropic community (www.fnih.org).

During the past three years, several public-private initiatives have been set up to speed up development of neglected diseases or to make drugs available to patients in poor countries. These include:

Medicine for Malaria Venture (www.mmv.org).

Global Alliance for TB Drug Development (www.tballiance.org)

Global Fund to fight AIDS, Tuberculosis and Malaria (www.theglobalfund.org)

Drugs for Neglected Diseases Initiative (www.dndi.org)

International AIDS Vaccine Initiative (www.iavi.org)

Global Alliance for Vaccines and Immunisation GAVI at WHO (www.who.int) Global Forum for Health Research (www.globalforumhealth.org)

The Bill and Melinda Gates Foundation (www.gatesfoundation.org/GlobalHealth/InfectiousDiseases/)

The Gates Foundation has awarded at least $3.2 billion in grants to global health organisations, including the Vaccine Fund, the Malaria Vaccine Initiative, and the International Vaccine Institute. It is too early to make a judgement about the productivity and cost effectiveness of these efforts.

Future trends

Today, ‘Big pharma’ is largely based on an old model, with each company running its own discovery, development, manufacturing, marketing and sales for the majority of its product pipeline and portfolio. External relationships tend to be opportunistic, but trying to do everything carries a high risk and investment.

Traditionally, ‘Big pharma’ has organised itself along functional lines, with separate functional units for each stage of the drug development and marketing process. This functional structure maps well to the blockbuster model. R&D operates with a distinct focus on creating blockbusters, which are then handed off to a flexible, commercial operation for launch. Other functions work to support R&D and commercial functions effectively and efficiently, with marketing serving as the bridge.

Rising costs of commercialisation, new data reveals a significantly higher cost of $1.7 billion than previously thought for discovering, developing and launching a new drug. Shorter exclusivity periods – increasing competition from ‘me-toos’ (ie, they are easier to create, receiving FDA approval and health insurance coverage) and patent protection increasingly under attack (ie, increasing country and EU pressures, state and federal backlash against perceived pharmaceutical company exploitation, and related societal pressures.

Companies have created

seventy percent of all “blockbusters” with significant prior experience in the relevant drug category. Prior experience helps companies design better trials and launch products more effectively, which in turn delivers more compelling economic results – increased probability for launch success and dramatically lower costs of developing and commercialising a drug.

Most of the industry top lines consulting firms have declared the end of the blockbuster model and era. The results of genomics, proteomics, HTS, combinatorial chemistry and robotics and automation will enhance R&D productivity in the next five years. Fewer products are available for licensing, discovery success rates are falling, sales force productivity is dropping and pricing pressure from payers continues to increase.

Strategic review, analysis and consulting firms have prompted big pharmaceutical firms to shift focus to targeting specific populations or disease areas and shift R&D resources to biologicals and monoclonal antibodies which have higher rates of success, use partnerships in all stages of drug discovery and development to reduce risks and share rewards and focus on disease and needs of the patients and operate as strategic business units like Johnson & Johnson. Some of the remedies suggested and even the J&J model has not worked in the past for some companies.

The writer is Pharma R&D Advisor, Geneva, Switzerland. E-mail: maggonk@lycos.com