Merck & Co’s cancer blockbuster Keytruda funds cutting edge rare disease R&D in UK

Merck & Co is enjoying blockbuster revenues as its cancer immunotherapy Keytruda is becoming standard of care in a range of cancers. But some of those revenues are helping British scientists develop drugs for rare diseases that big pharma deems too risky to invest in. Richard Staines spoke to Catriona Crombie, philanthropic fund manager at the UK charity LifeArc to find out more.

Getting drugs from the lab to the market is tough at the best of times, because of the high attrition rate in the development process.

What seems like a solid concept for a drug can be blown out of the water by an unforeseen side effect because of the huge complexity of the human body.

Getting drugs developed for very rare diseases, and certain drug classes such as antibiotics, is harder as big pharma companies and investors think there won’t be a return on any investment because of the risks of failure and low revenues from a small patient group.

Stepping into this gap is the UK charity LifeArc, which was formerly known as MRC Technology, the arm of the government funded Medical Research Council that specialised in getting drugs from the lab to patients.

Now an independent charity based at the life sciences hub near GSK’s base in Stevenage, Hertfordshire, LifeArc has no financial ties to the government and is funded through charitable donations – and revenues from Merck & Co’s cancer blockbuster Keytruda.

Set up in 1992, the charity assisted in the development of four drugs that have helped to set standards in several diseases over the last two decades.

Former MRC Technology drug Tysabri (natalizumab) eventually ended up as Biogen’s drug for multiple sclerosis, Actemra (tocilizumab) went to Roche as a treatment for rheumatoid arthritis, and Entyvio (vedolizumab) is marketed by Takeda for ulcerative colitis and Crohn’s disease.

But it was MRC Technology’s work in 2006 on a then obscure antibody known as pembrolizumab that has proved to be game changer for many cancer patients, and the charity’s balance sheet.

MRC Technology helped to humanise the antibody for a biotech called Organon, reshaping it after initial development in rodents to reduce the chances of the patient’s body reacting to it and neutralising its effects.

Organon was then acquired by Schering-Plough in 2007, which was in turn snapped up in 2009 by US-based Merck & Co.

Merck almost dropped the drug but decided to push on with development when trial results elsewhere began to suggest that cancer immunotherapies like pembrolizumab might become marketable therapies.

The rest is history – now branded as Keytruda, Merck & Co is raking in billions of dollars every quarter after it got approved in a diverse range of cancers over the last half decade or so.

Thanks to that initial work with Organon, MRC Technology was due royalties from sales of Keytruda. In 2016 the charity secured its medium-term financial future by selling a proportion of the Keytruda royalty income for £115.6 million.

The money has allowed the organisation to fund projects directly, and in 2017 it rebranded as LifeArc to reflect its role getting life-saving treatments to patients.

Last year, the charity announced its name change and the creation of two new funds worth a combined £30 million over four years – a philanthropic fund will provide grants to academic research, while a seed fund will invest in early stage therapeutics and biologic research.

LifeArc’s drug discovery operation is also playing a role in developing a new wave of antibiotics, another area that has been poorly served by the pharma R&D investment model as returns on such drugs are usually low.

Catriona Crombie, fund manager of the LifeArc’s philanthropic arm, told pharmaphorum that the focus is very much on projects that pharma, and biotech investors, would shun.

The emphasis is not to compete with these players but to “de-risk” the drug development projects so that they can be progressed in the lab or clinic.

The goal is to find the data that will act as a catalyst for further development in the clinic or lab, said Crombie.

“I want to focus this on areas not well served by other funders. That leaves us with early stage projects that are high risk, or ultra-rare conditions.”

“A number of projects will be co funded by charities or funded by us. You need to have reasonably deep pockets to fund translational research.”

The projects that are being funded are not yet in the public domain, as nearly all are still being trialled at universities, said Crombie.

Looking forward, Crombie said she hopes the work of LifeArc could also lead to changes in the way that health systems fund drugs for rare diseases once approved.

Gene therapies for rare diseases have started to hit the market, but prices have been sky high, such as Spark Therapeutics’ Luxturna (voretigene neparvovec) for a rare vision disorder that costs $850,000, or $425,000 per eye in the US.

US payers have been able to strike deals with Spark, but the concern is that as more and more expensive gene therapies hit the market, the cost to health budgets will become increasingly difficult to manage.

Crombie points out there are at least 7,000 rare diseases, so the potential spend on drugs for these conditions is enormous.

She said: “There is a lot of concern across the charity sector about payers. What we are looking at when we decide to fund a project is if there is a plausible route to patients. We would be reluctant to fund a project that nobody would be prepared to pay for.”

Philanthropy may play a role in funding these drugs – individuals with high net worth may offer a funding lifeline for patients with ultra-rare diseases that could be treated with a single shot of a gene therapy, Crombie said.

“In gene therapies you may be able to convince someone to pay for a manufacturing run that you could treat every patient with. You could pay for them with one shot hypothetically without having to fund them (through health systems).”

Through the Keytruda royalty big pharma is ironically funding research that would not be done using the conventional investment model, albeit indirectly.

But the money won’t last forever, and Crombie said that in the future philanthropists may have an increasingly important role to play in getting certain drugs developed.

“There are some good news stories about how humanity is working to solve these problems,” she concluded.

Anyone interested in working with LifeArc can contact the organisation here.