Celebrate_coverBioscience is a fundamentally important sector for the UK’s health and wealth. Back in June, the BIA published a report which aimed to unravel the stories behind just some examples of UK bioscience success. These are only a snapshot of the full spectrum of UK bioscience successes, past or ongoing, but help illuminate where UK bioscience is shaping scientific innovation and is delivering benefits to humanity. Over the next few weeks, we’ll be showcasing these stories on the blog, starting with Humira – the world’s top-selling medicine and its UK heritage.

Humira (adalimumab) is the world’s top-selling medicine. The treatment helps almost half a million patients across the world to live with a range of debilitating and often painful conditions, including rheumatoid arthritis (RA) and Crohn’s disease.

Humira’s target is tumour necrosis factor alpha (TNF-α), a protein that can cause excessive inflammation associated with auto-immune diseases like RA. In 2003 Humira became the first “fully human monoclonal antibody” to gain approval.

In the 1990s, TNF, and its potential as a drug target, were well understood. The issue was how to avoid the toxicity drawbacks of antibodies that were produced using non-human cell lines. The story behind how this challenge was overcome is a showcase for UK scientific excellence.

A new technology for making medicines

Working at the Medical Research Council (MRC)’s Laboratory of Molecular Biology in Cambridge during the 1980s, UK antibody pioneer and prize-winning scientist Sir Greg Winter and fellow scientist John McCafferty invented new techniques to create and isolate humanised and fully human antibodies for therapeutic use.

Key to Humira’s discovery was the “phage display” method. This uses special viruses called bacteriophages as vehicles to display proteins of interest (e.g. human antibody fragments) on their outside, so they can be screened for interactions with other proteins or molecules. Antibody “libraries” containing millions of different human antibody fragments displayed on phages are thereby used to isolate very targeted, specific leads with therapeutic potential. These fragments are then used to build full-sized antibodies using humanisation technologies.

Sir Greg and John McCafferty co-founded Cambridge Antibody Technology (CAT) in 1989, along with David Chiswell, to allow the phage display technology to be fully exploited to create new medicines.

The partnership that created Humira

Meanwhile, with phage display poised to revolutionise antibody drug discovery in the early 1990s, a group of scientists at BASF Bioresearch Corporation (BBC) (part of what was then the pharmaceuticals division of Germany’s BASF) in Worcester, Massachusetts, were looking for ways to produce fully human antibodies to TNF. They knew the target well, had lots of it, and already had a murine (mouse-derived) antibody to this target in clinical tests.

In 1993, BBC partnered with CAT to access its phage display technology. Thus began Humira’s gestation – first as clinical candidate D2E7 from early 1995, then, as the compound approached commercialisation, as Humira – HUman Monoclonal antibody In Rheumatoid Arthritis.

A patient self injecting a dose of Humira

A patient self injecting a dose of Humira

Overcoming the odds: Humira’s path to market

Humira’s journey from the CAT laboratories to a multi-billion dollar global blockbuster wasn’t a straightforward one. Few drug development stories are.

The research collaboration between the CAT team in Cambridge, UK and BBC in the US worked very well. Yet BASF was primarily a chemicals conglomerate and was not particularly interested in pursuing this compound developed by a research offshoot on the other side of the Atlantic. So at the very end of 2000, after a flurry of almost-deals with other players, BASF’s pharmaceuticals division, known as Knoll, was sold to Abbott Laboratories in a virtual auction.

By that time, D2E7 was already in the final stages of clinical development. Abbott’s management understood the compound’s potential value. Three years later, the regulators, too, saw what Humira could offer patients suffering from inflammatory disease – the drug was approved six months earlier than expected, without debate. Humira was a rare good news story for an industry often beleaguered by regulatory delay and clinical failure. Humira “is the most important drug launch in our 115-year history,” said Jeffrey Leiden, MD, PhD, then Abbott’s chief scientific officer and executive vice president of its pharmaceuticals division.

As sales took off, CAT and Abbott became embroiled in a fierce royalty dispute, but CAT held its ground. This UK biotech’s technology and expertise had been validated to an extraordinary degree. In 2005, AstraZeneca bought CAT for £702 million. Following Abbott’s decision in 2011 to separate into two publically traded companies, Humira is now manufactured and sold by AbbVie.

Helping patients and improving lives across multiple conditions

Humira approval timeline by indicationHumira’s full potential is still unfolding: AbbVie is testing the drug in a rare, painful chronic skin condition called hidradenitis suppurativa (sometimes referred to as ‘acne inversa’), for which there is no approved treatment or cure, and in uveitis, inflammation of the eye.

In 2014 Humira’s sales reached almost £12 billion and they are still growing. Humira’s success; and that of anti-TNF therapies more broadly, has also led to a deeper understanding of the inflammatory process, in turn helping create other therapies for inflammatory joint diseases – and further choices for patients.

Two decades after CAT helped create Humira, this drug continues to improve lives and break records.

Like to find out more? The full version of the Humira case study can be found in our report, “Celebrating UK bioscience: unravelling the stories behind UK bioscience success”.