It started with a belief

When Dr Judith Pool, then a research associate at Stanford University, first developed in 1964 a technique for producing cryoprecipitate from a single donor’s plasma in an ordinary blood bank, it represented a major improvement in the treatment for haemophilia patients.¹ Prior to this time, haemophilia patients could receive transfusions of fresh whole blood or fresh frozen plasma in hospital. Cryo from single donors became widely available for patients with haemophilia.

The advances with cryo sparked a wave of interest in plasma-based therapies and a handful of companies moved quickly to commercialise this new opportunity. Development of commercial fractionation technologies in the late 1960’s and 1970’s yielded lyophilised clotting factor concentrates that immediately raised the missing clotting factor to normal levels, could be carried with patients on trips and could be self-administered.²

For the first time, haemophilia patients could be treated prior to a bleed (prophylactically), reducing the likelihood of a bleed and the resulting joint damage.³

A partnership is born

It was at Baxter’s Travenol Laboratories that Wolfgang Marguerre and Robert Taub first crossed paths.

“That’s where I started getting a taste for medicine and plasma‑derived healthcare,” recalls Robert, who joined Travenol in 1973. In 1975, the year Wolfgang joined the company, Robert moved into the plasma derivatives business which Wolfgang was managing.

During these initial years, the two young managers formed a lasting bond based on trust and mutual respect. Their careers became ever more closely intertwined. When Wolfgang left Baxter in 1978 to take up a position as Senior Executive Vice President at French cosmetics giant Revlon, in charge of its plasma division, Robert followed a year later to become General Manager of the German subsidiary, again reporting to, and working closely with, Wolfgang.

An emerging health crisis for haemophilia patients

While factor VIII concentrates had brought new hope to patients with haemophilia, they also brought a new scourge: hepatitis. The factor concentrates were manufactured from pools of up to 40,000 donors, at a time before donor screening and virus testing were available.

Viral inactivation and removal techniques were also not yet implemented in manufacturing. By 1980, almost all patients being treated with clotting factor concentrates such as factor VIII had been exposed to hepatitis. It is thought that anybody who used a factor concentrate before 1985 was exposed to hepatitis C and most of these patients were infected with the virus.⁴ It was not until 1990, for example, that testing for hepatitis C was introduced.

In the USA, towards the end of 1980, a new blood borne disease – acquired immune deficiency syndrome (AIDS) – began to be observed. By 1982, no direct proof yet existed that showed that AIDS was infectious or transmitted by blood. No agent had been found and no tests existed to screen potentially infected persons.⁵ However, in 1982, the first death of a haemophilia patient infected with AIDS was reported in the USA and the first warning of the danger of contracting AIDS from contaminated blood products was published. This was followed in 1983 by other warnings in The Lancet and from the WHO which said that haemophilia patients should be warned of the dangers.⁶

Call to action: An urgent need for viral inactivation

Wolfgang and Robert were quick to understand and grasp the enormity of what was happening to the haemophilia community. Patients were being infected every day with hepatitis and HIV.

Confronted by the grim reality, they decided that they had to act fast to find a technology capable of inactivating these various pathogens.

Octapharma is born

Robert and Wolfgang decided to join forces and on June 2, 1983, they founded their company, called Octapharma – the name being a nod to factor VIII, in Switzerland. The two entrepreneurs had also become increasingly aware of the growing need for innovation in the plasma industry.

A chance discussion with a haematologist friend in Paris brought research being done at the New York Blood Center (NYBC) to their attention. “We thought the solvent / detergent (S/D) method had the potential to be a very elegant viral inactivation method for lipid-coated viruses like hepatitis and HIV,” remembers Robert. “In the S/D method, the solvent breaks down the lipid layer and the detergent inactivates the virus, but it does not affect the biological properties of the FVIII protein.”

Launching the team

Recognising the urgent medical need for virally inactivated clotting factor concentrates for haemophilia patients, Robert and Wolfgang decided to invest and work together with the team of scientists at the NYBC (which included Drs Bernard Horowitz, Richard Bonomo and Alfred Prince).  Recognising the great potential of S/D to deliver virally safe clotting factor concentrates, Robert and Wolfgang purchased a licence for the use of the S/D method from the NYBC.

At the same time, they hired Octapharma’s first full-time employee: Andy Smith, a protein chemist, who was working at Revlon’s fractionation plant in Illinois. Andy was quickly sent to the NYBC to study the S/D method with a view to further improving it and scaling it up for commercial production. Andy recalls the moment when they were able to test the S/D method: “We obtained a sample of the HIV virus. With some trepidation, we took it into the lab at the NYBC to test whether the S/D method could inactivate it. We were elated when we discovered that S/D killed the virus,” he says.

“So we could demonstrate that Octapharma had a process to kill both the hepatitis and HIV viruses, and could be the first company on the market with a virus-safe product.” Andy, who still works for Octapharma, then moved to Paris from where he commuted every week to the German Red Cross’s laboratory in Haagen to further refine his modified S/D method in a commercial scale.

First steps in manufacturing

Armed with a licence for the S/D method and Andy’s manufacturing process and know how, Octapharma began to work together with various European plasma fractionation companies. In return for providing access to the S/D method and know how, Octapharma received a certain volume of the ensuing virally inactivated FVIII concentrate on a contract manufacturing basis. In 1985, only two years after founding Octapharma with nothing but a dream to provide safer products for patients, the first virally inactivated FVIII concentrate produced using the S/D method – “octavi” – was made available to haemophilia patients. Wolfgang and Robert had delivered on their quest to provide the safe and efficacious product that haemophilia patients deserved.

Some 40 years later, the S/D method – as initially developed by the NYBC and then refined and perfected by Andy Smith and Octapharma – remains the current gold standard used by the plasma fractionation industry for safety from highly infectious lipid enveloped viruses,⁷ such as hepatitis B and C, HIV 1/2, as well as more recently emerging viruses such as West Nile virus, Chikungunya virus, Ebola virus, SARS-CoV-2 and many others.

Those early years were challenging. Wolfgang recalls, “We started with nothing and had to push hard to get the business off the ground. At the beginning, I only had a desk, the same desk I still work at today, and little else.” Nevertheless, the hard work and long days and nights paid off.

Octapharma grew steadily and, in 1989, bought our first fractionation plant in Vienna. “This transformed the company,” says Wolfgang, “from a 12-person company; suddenly we had 150 employees, and with our own production facility, we could get to work further improving and developing new plasma-derived medicines for patients.”

In 1995, after more than a decade together building the company from nothing, Octapharma’s two founders went their separate ways, with Robert agreeing to sell Wolfgang his stake in Octapharma. Robert went on to enjoy an extremely successful career in his various endeavours, including the sale of his company Omrix Biopharmaceuticals to Johnson& Johnson in 2008.

By 1995, Octapharma had annual sales in the region of €100 million and, despite many challenges along the way, was on a stable long-term path to continued growth.

Still driven by our vision…

Today, the company operates five production sites in Europe and collects most of its own plasma through more than 190 plasma donation centres in the USA and Germany. Octapharma has a broad portfolio of 13 medicines (both plasma-derived and our recombinant FVIII, Nuwiq®) across our three therapy areas of Immunotherapy, Haematology and Critical Care, and employs more than 11,000 people around the world. With expected revenues of more than €3 billion in 2023, we are one of the largest human protein manufacturers in the world, providing medicines to hundreds of thousands of patients annually in over 118 countries.”

“When I started this company together with my business partner Robert Taub in 1983, we could never have imagined that Octapharma would achieve such incredible sustained success,” reflects Wolfgang. “It started with a belief that we could provide haemophilia patients with a safer, higher-quality FVIII concentrate,” says Wolfgang, who remains Chairman and CEO of Octapharma some 40 years later. “Today, driven by a vision to provide new health solutions advancing human life, we continue to find new ways in which to help people with life-changing medical conditions and to further grow our business.

We remain as determined as ever to further improve and grow, so that we can provide our life-changing medicines to even more patients around the world.”

References

1. ^{Kasper, CK “Judith Graham Pool and the Discovery of Cryoprecipitate”, Haemophilia (2012) 18, 833-835.}

2. ^{Evatt BL, “The tragic history of AIDS in the hemophilia population, 1982-1984”, J Thromb Haemost 2006; 4: 2295-2301.}

3. ^{The Contaminated Blood Scandal”, https://haemophilia.org.uk/public-inquiry/the-infected-blood-inquiry/the- contaminated-blood-scandal/}

4. ^{“What is the contaminated blood scandal?”, https://www.factor8scandal.uk/contaminated-blood-scandal}

5. ^{Evatt BL, “The tragic history of AIDS in the hemophilia population, 1982-1984”, J Thromb Haemost 2006; 4: 2295-2301}

6. ^{“The Contaminated Blood Scandal”, https://haemophilia.org.uk/public-inquiry/the-infected-blood-inquiry/the-contaminated-blood-scandal/}

7. ^{“Guide for the Assessment of Clotting Factor Concentrates 3rd ed (2017).” Prepared by Albert Farrugia, BSc, PhD for the World Federation of Hemophilia; https://www1.wfh.org/publication/files/pdf-1271.pdf}