Benzos to Breakthroughs: Bill Burns on Roche's Transformation

There are pivotal moments that stick in the mind of any longtime CEO. Some are good, some are bad, all are memorable.

For Bill Burns, three defining snapshots encapsulate the highs and lows of his nine-year journey at the helm of Roche’s pharmaceutical division. A candid conversation in a Japanese bar with a fellow big pharma CEO questioning Roche’s bold investment in monoclonal antibodies. The triumphant standing ovation for Herceptin at ASCO in 2005, celebrating its revolutionary impact on breast cancer treatment. And the intense scrutiny in 2006, when New York Senator Chuck Schumer called for the suspension of Roche’s Tamiflu patents to combat the bird flu crisis.

Burns’ career has been woven into key advances and challenges for the health care industry over several decades; cancer breakthroughs, pandemic preparedness and response and, latterly, the antimicrobial crisis.

As this year’s Scrip Awards Lifetime Achievement Award winner, it is no surprise that Bill Burns has made his mark in the pharmaceutical industry over many years. On receiving the award, Burns describes as “all a bit humbling, how quickly 50 years can pass.”

As an economics graduate, Burns’ entry into pharma was not deliberate. He joined Beecham as a management trainee in 1969, by chance entering the pharmaceuticals division, a move he describes as “the best mistake of my life” and spent 17 years working his way through the commercial path in the UK and Japan.

He joined Roche in the UK in 1986 to lead the UK pharma sales and marketing division, at the point when it lost 60% of its turnover because of benzodiazepines being taken out of state reimbursement. He then moved to head the UK pharmaceuticals division in 1988 and quickly moved to international responsibilities in 1991 in Roche’s Basel HQ as head of strategic marketing and business development. 

Having planned for a five-year strategic sojourn, Burns, a proud Scot, still lives in Switzerland. “The classic expatriate assignment,” he explains with a smile.

In Basel, Burns curated a culture shift to take a company that had been strong in primary care into hospital and specialty care on a cohesive international strategy.

He continued to take on more responsibilities within Roche, and in 1998 led the European pharma division and latterly the international pharmaceuticals branch. Having become a board member of Genentech and Chugai Pharmaceuticals, he headed the global pharmaceutical division from 2000. During his time in the role, pharmaceutical sales doubled, as did operating profit and market capitalization, and the pipeline was reinvented.

While the Burns management era saw significant investment in pipeline modernization, he also changed the structure of the company, a strategy he said had been “cooking for some time.” On the move from primary care to specialty care, he divested a significant number of older and smaller products along with the manufacturing structure and sales field force that went with them. “There had been a master plan to it,” he explained. “It all worked extremely well in unlocking the change in the share price and the viewpoint of the city because the pipeline was seen to be more modern. Still to this day, the company is very strong and on its way forward,” he said.

One of the last major changes involving Burns was the $46.8bn acquisition of Genentech that made it a wholly owned subsidiary in 2009, almost 20 years after its first majority stake was bought in 1990. Burns’ successor Pascal Soriot was charged with the integration of the biotech engine into Roche proper. Burns ultimately spent nine years leading Roche Pharma, and retired shortly after the transaction was completed.

The Usher To A New Era Of MAbs

During his years at the top of Roche’s pharma division, Burns spearheaded the company through the industry’s “new era of monoclonal antibodies”, of which the Swiss major played a major role.

Having inherited rituximab through the majority stake acquisition of Genentech in 1999, Burns recalls a board meeting discussing the fortunes of what the company believed may be a $600m drug. It was the first monoclonal antibody (mAb) approved for hematology, and since that approval in 1997 for B-cell non-Hodgkin lymphoma (NHL), it has improved outcomes in all B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia.

Roche developed Rituxan for other indications beyond cancer including rheumatoid arthritis. It also combined rituximab with other treatments to enhance its efficacy. Subcutaneous formulations of rituximab broadened its use further. At its peak, Rituxan earned around $7bn in annual sales for the company.

With the wind in its mAb-shaped sails, Roche followed the success of Rituxan with another mAb, trastuzumab, marketed as Herceptin for late-stage breast cancer.

To invest so heavily in mAbs at the time was a “big bet.” Burns recalls the moment a fellow pharma CEO remarked to him that focusing on monoclonal antibodies was unnecessary, suggesting that small molecules could target any issue, a perspective that has since been disproven as clinical oncology has evolved. “What I’ve seen over the years is that wherever you’ve got a group of people making a decision on research and development, you have all their skills and all their prejudices,” said Burns.

“In oncology today, the more we know the more we don’t know,” he said. “It was thought that there were about 200 targets for monoclonal antibodies. Well, we haven’t even scratched the surface yet. With biphasic monoclonals, with targeted response, and with ADCs, it’s amazing how much of a difference we can make in cancer, but also in many other areas of medicine.”

Herceptin, Avastin And Beyond

Burns distinctly remembers a standing ovation at the American Society of Clinical Oncology (ASCO) in 2005 for trastuzumab results in a large patient trial for breast cancer patients with the particularly aggressive HER2-positive tumor, which accounts for around 20-30% of all breast cancers. “It was a huge undertaking, and a huge moment for the fight against breast cancer,” he recalls. This success took place against a backdrop of questions from the financial community asking why Roche was moving from primary care and GP medicines into specialty care. This “niche” is thought to have peaked at around $5bn in annual sales.

Rounding out Roche’s mAb success was Roche’s cancer work horse, the VEGF inhibitor Avastin (bevacizumab). It was approved in 2004 for metastatic colorectal cancer, followed by approvals in a number of other cancers. Sales peaked in 2014 at $7.1bn before patent loss made way for biosimilar competition.

Roche’s basic, primary patents for Rituxan, Avastin and Herceptin have expired. The first biosimilar versions of Herceptin and Avastin were launched from mid-2019 and the first biosimilar versions of Rituxan in late 2019. However, these continue to be money makers for the company, with Rituxan earning $1.1bn in 2023.

“Today, nearly every big pharma is involved in some way or another in monoclonals, but it took a long time for people to adopt. In science, some of the breakthroughs we have can take decades until we find the right way of using them, and then we can really unlock the benefit for patients. This is a long game,” said Burns.

The Tamiflu Years

In 2009, the H1N1 bird flu pandemic was making its voice heard across the world. There was extensive pandemic response planning at all government levels, and preparedness efforts revolved around “clamoring” for Roche’s Tamiflu (oseltamivir) and, to a lesser extent, GSK’s Relenza (zanamivir) and BioCryst Pharmaceuticals’ Rapivab (peramivir).

Up to 2009, Tamiflu had only been a commercial success in Japan, Burns explains, and Roche routinely manufactured around 10 tons of product a year.

The company was in uncharted waters, and had to make quick decisions, the first being where to allocate existing stock, which it offered on a ‘first come first served’ basis, and which was subsequently taken by world governments. The second decision was to set a worldwide price, which was lower than any other firm and even lower for the 28 least developed nations on the planet, as defined by the United Nations.

“It’s decisions like that where you think, are we doing the right thing? My last call of the evening was always to the project manager to reflect on the day. We would always challenge ourselves “are we doing the right things,” recalled Burns. “If either of us walked out of our home in the morning and were confronted by national TV media, would we pass the red face test?”

Politicians became involved with the crisis, with New York senator Chuck Schumer telling the media that other companies could manufacture Tamiflu much quicker and calling for the patent to be stripped from Roche for the duration of the pandemic to up manufacturing levels.

“There were a number of months where the main boardroom of Roche was ‘mission control central’,” recalls Burns, likening it to a strategic war room. “We were making it up as we went along, trying to get that [Tamiflu] production going.”

The starting material for Tamiflu is shikimic acid, which is primarily derived from the wild form of Chinese star anise plant only found in four districts in the country and was crucial in the synthesis of oseltamivir.

The fervor for Tamiflu led Burns to set up a dedicated website inviting anyone with ideas on how to contribute to the supply chain to come forward. This open approach allowed them to tap into a global network of potential suppliers and partners. It also had to develop a new chemical process to produce Tamiflu at scale involving significant R&D efforts to optimize production. It opened up new production sites to increase capacity to address concerns about domestic supply.

Roche managed to scale Tamiflu (oseltamivir) production to nearly 500 tons annually, enough for five to 10 million people. “It didn’t matter which stone we unturned. There were new experiences, new findings, new politics to deal with. That was an intense two-year period,” he recalled.

“It has been fascinating to reflect on, with the COVID crisis, that institutional memory is very poor,” he said. “It was interesting to see that, whether it was at WHO or whether it was with world governments. Very little has been learned.”

Action On AMR

As with many ex-pharma CEOs, Burns is still passionate and involved in the medicines of today. He has held positions on the advisory board for the Chugai International Council, Wellcome Trust, the UK’s Institute of Cancer Research, and Novo Holdings in Denmark. He is currently on the advisory board, chair or vice-chair of seven companies across Europe, USA and Australia.

The thrill of seeing ideas becoming medicines is clearly still in his blood as he talks passionately about the future of antimicrobial resistance (AMR), and the urgent and coordinated action needed from the global pharmaceutical industry, governments, and health care systems. Without significant changes in how antibiotics are developed, manufactured, and distributed, AMR could “bring a standstill to modern medicine as we know it,” he said.

One of Burns’ first roles as a product manager for Beecham was to launch Amoxil (amoxicillin). Initial expectations were modest since the chemistry was very similar to ampicillin. Investigations by Burns and work with a microbiologist led to a recognition of a faster kill rate against bacteria with a simpler dosage schedule. Following initial success, research then led to combining this with the first beta-lactamase inhibitor that we know today as Augmentin. “I’m sure that Glaxo is still getting a fair amount of revenue out of those products,” he joked.

Today, his interest in antibiotics has re-emerged and he is chairman of the industry-sponsored AMR Action Fund, which invests in companies that are creating therapeutics for WHO priority pathogens. Its goal is to help introduce two to four new antimicrobials within the next decade and establish a sustainable ecosystem of investment and innovation.

Burns stresses the need for a revised business model for antibiotics, suggesting a Netflix-style subscription approach to incentivize companies to develop new antibiotics without relying on high-volume sales. High up on his list of AMR priorities is the need for harmonized regulatory approaches across different countries to address AMR effectively.

Throughout his career, Bill Burns has demonstrated a commitment to purpose-driven enterprise, emphasizing the satisfaction of working in medicine and making a tangible difference in people’s lives. His journey from studying economics to becoming a pharmaceutical industry leader underscores the importance of “finding one’s passion and pursuing it relentlessly.”

As the pharmaceutical landscape continues to evolve, Burns remains optimistic about the future of medicine. “Science couldn’t be more fascinating than it is today, which is probably one of the reasons I’m still so involved,” he said.