The Biotech Effect

It was once derided as the stuff of science fiction, but in recent years, biotechnology has emerged as an important growth area in pharmaceuticals. As understanding of biological systems has forged ahead, pharmaceutical companies have made increasing use of biotechnology in discovering and manufacturing new medicines.

According to Nick Staples, director of corporate affairs for pharmaceutical company Protherics, it is in its impressive variety that biotechnology holds such promise for the pharmaceuticals industry. A plethora of technologies are grouped under the umbrella of biotechnology which are targeted at different levels and offer numerous different possibilities to tackle disease.

“Biotechnology represents a range of technologies, some suited better to one disease state and others to another,” explains Staples. “In short, each needs evaluation individually for each circumstance but the sheer diversity of biotechnology means that it is very rarely inappropriate for consideration.”

According to Chris Reilly, global vice president of discovery, strategy and performance for AstraZeneca, it is now recognised that biotechnology unquestionably offers important benefits for the pharmaceuticals industry by presenting alternatives to other therapies.

“The inherent advantages of biopharma are that it allows you to pursue therapies against targets that are not small molecule therapies, for example by targeting protein-protein interactions and targeting GPCRs (G-protein coupled receptors),” he says. “It has to be recognised that antibody therapy does not fit everyone and that small molecule therapy may be more appropriate for some people due to cost considerations.”

The fast growth of biotech

As its advantages have become ever more apparent, the pharmaceutical sector’s interest in biotechnology has grown significantly.

“Biotechnology has exploded across the industry. It started to emerge in the mid 1990s, incrementally gathering speed as more products were approved in the last ten years,” says Reilly. “The pharmaceutical industry is increasingly embracing large molecule products and concepts.”

Today most big pharmaceutical companies are pursuing biotechnology either in house or by using an in-licensing strategy.

However, Staples says much of the original drive to apply biotechnology to pharmaceuticals came from smaller players rather than large pharmaceutical companies, which traditionally focused on the development of drug candidates using small molecules while the smaller entrepreneurial biotechnology companies focused on the development of biologically derived candidates such as monoclonal antibodies, antisense, gene therapy and stem cells.

The dynamic has now changed as many big companies have now acquired biotechnology companies or have developed ‘biotechnology divisions’ of their own.

“Big pharmaceutical companies were late adopters of biotechnology based products, continuing to rely on mass screening of new chemical entities,” says Staples. “However, around the time of the Human Genome Project, there was a ‘land grab’ for the new technologies as big pharmaceuticals tried to catch up paying high prices to access technology platforms in areas such as genomics and high throughput screening.”

Winning over the market

Nonetheless, notwithstanding the undoubted future promise of biotechnology, there have been doubts about the extent to which the high prices paid by big pharmaceuticals were justified in the short term.

In general terms these have failed to add the value originally anticipated as turning knowledge into safe and effective drugs is still a complicated, lengthy process. However, a wave of exciting monoclonal antibody products was being developed, and these were quickly partnered with big pharma which demonstrated the increasing commercial opportunity for biotechnology.

By the early 2000s AstraZeneca had already realised the critical importance of biotechnology, making a number of strategic investments in biotech companies, Abgenix in 2003, Cambridge Antibody Technology in 2006 and culminating in its acquisition of US biotech firm, Medimmune in April 2007 for £15bn.

“Medimmune is a very large biotech company with good discovery skills, commercial skills and development skills,” says Reilly. “It also had good maturing capability. We are now one of the ten largest biopharma companies in the world with a rich armoury of new technology, comprising a full suite of technologies, small molecules, antibodies and vaccines to create new human medicines.”

It is a measure of the importance AstraZeneca attaches to biotechnology that Reilly says he hopes that a full quarter of its portfolio would be biotechnology in the next three years, and expects similar thinking in the rest of the industry.

Currently, AstraZeneca produces a number of medicines which were developed using biotechnology including anti-TNFs (tumour necrosis factor) which are widely used for rheumatoid arthritis and psoriasis and Avastin, used for the treatment of cancer. In addition, Medimmune’s Synergis is used to treat premature infants at risk of death from the RSV virus.

According to Staples, Protherics’ focus is not on technology per se but very much on products and particularly those which fit with its focus on critical care and cancer. Staples said it expects to continue growing its portfolio across a range of technologies through M&A, partnering and in-licensing.

Protherics acquired Enact Pharma in 2003 and gained two cancer products: Voraxaze™, a recombinant enzyme for methotrexate (MTX) overdose, and Prolarix™ an exciting prodrug for liver cancer.

In December 2006 it acquired MacroMed Inc, a privately owned speciality drug development and manufacturing company based in the US, for its lead product OncoGel™ for the treatment of oesophageal and brain cancers.

In addition to these acquisitions it has in-licensed IP from Glenveigh Pharmaceuticals LLC for the use of DigiFab™ and GSK’s Digibind® in the treatment of pre-eclampsia and eclampsia and in-license IP from Advanced In Vitro Cell Technologies for the use and co-development of Acadra™ (acadesine) in the treatment of B-cell chronic lymphocytic leukaemia (B-CLL).

At its main manufacturing facilities in Wales, Protherics manufacturers a range of biopharmaceutical products, including polyclonal antibody products, CroFab™, DigiFab™ and ViperaTAb™, as well as the manufacture of CytoFab™ for clinical development. It has additional manufacturing facilities located near Adelaide, South Australia where it raises the polyclonal antibodies used in these products and a facility in Salt Lake City where it manufactures OncoGel™.

It is also working on a number of new products using biotechnology. AstraZeneca’s phase 2 study of CytoFab™ in severe sepsis is expected to report towards the end of the calendar year, providing an important near-term event for one of the company’s key value drivers. CytoFab is a polyclonal antibody based product designed to neutralise tumour necrosis factor alpha and is being developed as a treatment for severe sepsis. The body’s response following severe infection often involves the
release of high levels of molecules called cytokines that cause inflammation. The resulting systemic inflammatory syndrome, referred to as sepsis, is a life-threatening condition which affects an estimated three million people a year worldwide, of which up to 30% will die from multiple organ failure.

In April it said that its placebo-controlled phase 2b Digoxin Immune Fab (DIF) Efficacy Evaluation in Pre-eclampsia (“DEEP”) study in severe pre-eclampsia met one of its two primary endpoints. The DEEP study results, along with data from further analyses, are under review by a potential licensing partner. Data from the study will be presented at international conferences later in the year, and guidance on the future of the programme is expected before the end of 2008.

In June Protherics announced the start of a phase 2a proof-of-concept clinical study of Angiotensin Therapeutic Vaccine (ATV), one of its key value drivers, in 124 patients, with mild to moderate hypertension. The study will assess the effects of ATV, which includes its new proprietary adjuvant, CoVaccine HT™, on blood pressure and antibody response, in addition to safety and tolerability. The blood pressure results are expected in the first half of 2009.

Biotechnology’s place in the pharmaceutical industry is assured, that much is clear. But according to Staples, there is still uncertainty about the precise role it will play.

“I think it is safe to say that biotechnology is most definitely here to stay and is being increasingly integrated into the way large pharmaceutical companies function and develop new drugs,” he says.

“How and where biotechnology will exist is harder to say, as big pharma looks to reinvent itself and investors in smaller companies shun the long timelines and risk of drug development. Biotechnology and our understanding of biological systems can solve these issues in time, but it remains a
pressing problem.”