Personalised medicine: quality not quantity

According to Tony White, CEO of Applera, the Human Genome Project suggests there are more than 10,000 drug targets; up to the end of the 20th century, the entire pharmacopoeia was based on just 500. The HGP data needs to be assimilated, but with 30,000 genes and five million single nucleotide polymorphisms there are clearly endless combinations that can affect individuals' health and response to medicines: there is no such thing as an average patient.

At present, many therapies only work in 40-60% of cases. Conference Chairman George Poste, CEO of Health Technology Networks, believes there is an urgent imperative to improve the rational use of prescription medicines. These are the fastest-growing segment of healthcare costs, but suffer from massive inefficiencies, such as futile prescribing, adverse drug reactions (ADRs) and non-compliance.

At present, only 10% of Phase I products ever reach the market. This low success rate is one factor behind the $800 million+ that it costs to develop each commercialised product - only 30% of which are actually profitable. And of the NDAs approved in 2002, only 22% were for new molecular entities, with the majority being made up of line extensions, new formulations etc.

Klaus Lindpaintner, Head of Roche Genetics, said 'Big Pharma' was now spending a higher proportion of its R&D spend at the preclinical stage. Much of this research had previously been left to academia or smaller companies, but with new technologies, Big Pharma often started at square one. As well as target identification and assessment and the production of biopharmaceuticals, Lindpaintner commented on the value of biomarkers at the middle stage of development. These may "de-risk" some projects, for example:

Overall, pharmacogenomics should make drug development faster and cheaper, thereby increasing the profit from each product. Patients will be selected using specific diagnostic tests, and only those likely to benefit from treatment enrolled into trials, making them smaller. Registration success rates are also likely to be higher, leading to an increased flow of new products.

Many industry observers have stated that the era of personalised medicine will be the death of the blockbuster, but this view was challenged at the conference. The success of Novartis' Glivec was highlighted, and Genentech's Herceptin has annual sales in excess of $500 million, even though it is only suitable for the 25-30% of women who have HER2+ breast cancer. The corresponding diagnostic test also generates its own revenue.

Serono's Senior Executive VP of Research Timothy Wells said that while Big Pharma was now often viewing blockbusters as $3-5 billion sellers, the middle ground mustn't be overlooked and could be a lucrative niche area for biotechs: $1 billion in sales meant 100,000 patients were willing to pay $10,000 a year for treatment.

Lindpaintner also demonstrated the wider value genomic research can have. By investigating mature onset diabetes of the young, a very rare form of the disease with a strong genetic component, Roche discovered an activator of glucokinase. The company found that the activator lowered glucose levels in all diabetes patients - i.e. it had gained a fundamental insight into glucose metabolism. The compound is now in Phase II trials.

Smaller markets, but premium prices

A number of speakers said current pharmaceutical industry margins were not sustainable. Cost-containment measures are increasing, and many presenters said the overall value to healthcare and cost/benefit ratio of drugs would become the most important factor when deciding treatment strategies.

Nevertheless, by having strong claims for the efficacy and safety of genomic products, companies would be able to maintain premium prices. The use of genetic data may even become mandatory: the FDA is already looking at pharmacogenomic findings, and the drug approval process is likely to become more arduous thanks to new technologies that will scrutinise product safety further.

Celltech CEO Goran Ando, meanwhile, noted that fewer players in each therapy area could lead to higher profits. There will be knock-on effects too, such as reduced direct-to-consumer advertising, currently a major expense. Less tangible, but perhaps no less important, more effective and safer drugs could enhance the reputation of the entire healthcare industry.

PBMs likely to join the debate...

Ando said biotechs should get involved in healthcare debates:

He said the industry should pick the right battles when it came to pricing and reimbursement: TNF inhibitors such as Enbrel and Remicade have changed the lives of rheumatoid arthritis patients, and thus their use is quite high even in regulated markets like France. Insurers and national health services should be more willing to pay for safe and effective drugs, and patient compliance would increase.

Poste pointed out that four US pharmacy benefit managers are collaborating on an ADR database, and believes they are likely to use the data to lobby companies and the FDA for more use of pharmacogenomics. Bigger pharma companies are already archiving DNA samples from clinical trial participants in case ADR problems arise later on: as drugs usually only cause severe reactions in one patient out of every 75,000, many ADRs are not seen until after launch. In the US there are 2-2.5 million ADRs each year, including 60-150,000 fatalities.

...which will continue

There are a number of social, medical and legal issues that need to be discussed, including how to deal with:

Big Pharma would also have to make a number of adaptations if personalised medicines are really going to flourish, as they will require different infrastructures and business models. The general consensus, however, was that more forward-looking companies will embrace pharmacogenomics: GlaxoSmithKline is opening a seventh Centre of Excellence for Drug Discovery focusing on biopharmaceuticals, while Amersham agreed to a takeover by General Electric to bring it the critical mass needed to be a pioneer in the area of personalised medicine.

Closing the conference, Poste said that while great scientific strides had been made, there were still therapeutic gaps. In his view, the most pressing is anti-infectives, but pharmacogenomics could play a role in helping with many of the disorders afflicting ageing Western populations, including neurodegeneration, 'diabesity' and insomnia. For the sake of the biotech industry's reputation, however, it was important that the public be educated about the risks involved in drug development, and expectations managed to avoid cycles of hype and disappointment.

This article was written by Selena Class, Deputy Executive Editor of IMS Company Profiles. IMS Global Consulting can help biotech or pharma clients grapple with the challenges of today's shifting healthcare arena, including the impact of technologies such as pharmacogenomics. Please contact Guy Bate with any queries in this area.