Hope on the horizon for families of thousands of Alzheimer’s patients

Michael O’Connell heads a small team, just 11 people. But that group holds out hope for thousands of Irish patients suffering from the early stages of Alzheimer’s disease, and their families.

Biogen, the company of which he is country head in Ireland, has a potential breakthrough treatment for a disease that hollows out loved ones, leaving them confused and without the memories that are central to all of our lives. And it is not just an aspiration, a piece of research that has potential for some time in the future. Leqembi, the drug developed by Biogen and its Japanese partner Eisai, is currently before regulators in both Europe and the United States seeking marketing approval.

A cure for Alzheimer’s or, rather, something to stop the memory-sapping disease in its tracks is the Holy Grail of modern medicine, a treatment for one of the few areas left where the clinical option is largely care.

“Alzheimer’s probably impacts about 50,000-55,000 people in Ireland and a huge population in America,” O’Connell says. “We’ve seen so many advances in medicines over the years and this is the one area where lots of companies have had research that failed at the final hurdle or just haven’t shown the clinical benefit.”

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That includes Biogen, which thought it had a winner on its hands just under two years ago with another Alzheimer’s drug, Aduhelm. Concerns over the way it was approved by the US Food and Drug Administration (FDA), which led to the resignation of several FDA advisers in protest, as well its very high price and serious side effects quickly saw it restricted in the US only to clinical trial patients. In Europe, the European Medicines Agency (EMA) rejected its use.

Any breakthrough will be huge, because not only is it an unmet need from a societal perspective, the cost of treating Alzheimer’s in society is huge

—  Michael O'Connell

“It’s a really challenging area, so obviously anything that’s beginning to show positive results is very exciting for the community involved because of the unmet need,” O’Connell says. “Any breakthrough will be huge, because not only is it an unmet need from a societal perspective, the cost of treating Alzheimer’s in society is huge. But you have to always proceed with caution, because everything in the past has got so far, and then they didn’t.”

Assuming Leqembi avoids the pitfalls that downed Aduhelm, when can those Irish patients – or at least those whose Alzheimer’s is at an early stage – expect to get access to the drug?

Pinch point

Biogen has only just submitted its data to the European regulator. It expects an outcome in the first quarter of next year. But that’s only the first stage. The company then has to negotiate with each EU state. In Ireland’s case, there will be a rapid review application, followed by a health technology assessment and then, critically, horse-trading over price, which is generally the pinch point.

“Typically, I think an oncology product is taking about two years [to secure approval],” O’Connell says, so 2026 if all goes well.

Access brings us to O’Connell’s other hat – president of the Irish Pharmaceutical Healthcare Association, the Irish industry group of research-based pharmaceutical companies investing in new medicines, as opposed to generic copies of existing medicines that have come to the end of their patent protection.

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“If I look back over my 33 years [in pharmaceuticals], probably the number one issue has always been timely access to medicines [for patients] and it hasn’t changed. But I think we are now at an inflection point for a couple of reasons.

“First of all, there are the advances in science, into cell and gene therapy. We’re not talking about small molecules any more, which was traditionally what existed when I came into the industry. We’re dealing with far more complex, complicated medicines and particularly in areas of unmet need. So obviously we have to sit back and look at whether we are ready in terms of how to manage that going forward.

“We’re seeing also the sheer volume that’s coming through.”

Funding is key, he says, adding: “In fairness to this Government, they’ve invested over a hundred million in the last three budgets, which is really welcome.”

The second element, he says, is the process of approving medicines for Irish patients. A report published by Minister of Health, Stephen Donnelly, on Friday said more than one-third of all new drug approvals take more than two years to complete, despite a legal requirement allowing 180 days for the process, unless additional information is required.

The Minister is due to open Ipha’s annual conference next Thursday at which the report is likely to loom large.

Difficult balance

“I’m encouraged personally by some of the conversations I’m having lately with some of the key stakeholders in the whole reimbursement system,” O’Connell says. “Collectively, we have got to sit down and look at the process and say, how can we make this fit for purpose for the next five years, for the next 10 years? And I think there’s a willingness to do that.”

It’s a difficult balance. Prof Michael Barry, head of the National Centre for Pharmacoeconomics, which assesses new medicines for value for money, noted in a recent interview that total drug expenditure in the Irish system would be €4 billion by 2027.

The innovative medicines that Mr O’Connell’s Ipha members produce account for a lopsided share of that, with Prof Barry saying 1 per cent of all prescription items account for 40 per cent of medicines expenditure.

The Ipha head accepts that affordability will always be an issue for the payers – in Ireland’s case, the HSE and the Department of Health – especially with more complex drugs, cell and gene therapies and medicines for very rare diseases being priced well ahead of what older drugs would have been.

CV

Name: Michael O’Connell

Age: 58

Position: President, Irish Pharmaceutical Healthcare Association (Ipha) and country manager, Biogen

Family: Married to Eimear, they have four daughters – Jessica, Alison, Erica and Emily – and very recently a first grandchild, Jamie

Interests: He’s been a Dromtariffe GAA club man for close to 50 years and stills serves on the sideline as team medic to both the men’s football and hurling teams every week. That aside, he’s partial to a round of golf at his local club, Kanturk, and walks daily with Eimear

Something you might expect: He’s in favour of the move to video calls that the pandemic encouraged as it cuts down dramatically on his time in airports

Something that might surprise: He started his career as a general nurse

“I think is a part of the discussion, and that’s why discussion is important, because these are far more complex [drugs]. And the way we work with the payers in the future has to be very different from the way we did in the past… and I think the industry needs to be open to that.”

The report on how to assess new medicines on the Minister’s desk is not the only document looming large on Ipha’s horizon. The European Commission is also scheduled to publish a new pharmaceutical strategy by the middle of next month, looking at issues such as security of supply, access and intellectual property (IP).

“What we hope to see is that that there is continuous support in terms of incentives around IP that will allow [companies to] continue to invest in areas that have unmet need,” says O’Connell.

“We see here in Ireland that we have a significant pharmaceutical presence here in terms of employment, manufacturing and everything else. Anything that kind of changes the landscape in pharma or makes it more difficult, obviously, is something that is more challenging.

“There are a lot of governments who say, let’s protect IP in the right way but also let’s get actual access to people as well. So let’s watch and see what happens.”

Love of Gaelic games

Six months into his two-year term of office, O’Connell clearly has a full in-tray. It’s a long way from his early years in Cork. His mother enrolled him in St Brendan’s in Killarney, known as The Sem – O’Connell suspects she was drawn by its reputation as a production line for seminarians. But he was more taken by his experience volunteering as a teenager in local hospitals.

When I finished my general [nursing], the pharmaceutical industry was really opening up in Ireland and they were particularly looking for nurses at the time

—  Michael O'Connell

What St Brendan’s did give him was a lifelong love of Gaelic games. His PE teacher in Brendan’s was Kerry football legend John O’Keeffe, part of the four-in-a-row team of the late 1970s – a time that coincided with O’Connell’s time in the school.

O’Connell qualified in both general nursing at St Michael’s Hospital in Dublin and psychiatric nursing at St John of God’s in Stillorgan.

“When I finished my general [nursing], the pharmaceutical industry was really opening up in Ireland and they were particularly looking for nurses at the time. You were in healthcare... You understood the system.”

Bristol-Myers Squibb (BMS) came calling for O’Connell through a connection made on the sporting field rather than in the lab, with the offer of a sales job back in Cork. He never looked back, rising through the ranks, ultimately to head BMS’s Irish operation before moving to Biogen.

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Biogen is not one of the manufacturing powerhouses of Ireland’s pharma sector but it is one of the oldest biotech pharma companies, with a long history of developing therapies for multiple sclerosis (MS).

Those therapies included Tysabri, a drug developed in partnership with what was then Ireland’s largest indigenous drug company, Elan. Following Elan’s implosion triggered by off-balance-sheet accounting issues, Biogen bought out the remaining rights to Tysabri, which remains the company’s top-selling medicine.

Biogen is also the maker of Spinraza, a treatment for the genetic muscle-wasting disease spinal muscular atrophy (SMA), which was eventually made available to Irish patients only after a concerted patient-led campaign.

Traumatic

For the past 10 years, the focus has shifted more towards Alzheimer’s. The failure of Aduhelm was traumatic for the company, with chief executive Michel Vounatsos stepping aside. But it cast few ripples in the company’s European operations.

“We hadn’t a regulatory product so, from our perspective, it was that terrible term ‘business as usual’,” O’Connell says. Instead, Biogen Ireland focused on its MS therapies and Spinraza as well as its portfolio of biosimilars (copies of modern biologic drugs, derived from living organisms, but not precise copies in the style of a generic drug).

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Vounatsos was replaced last November by former Sanofi boss Chris Viehbacher, as Boston-based Biogen looked to tap into the secrets of his success in reshaping the French drug giant to refocus its business, which currently has 35 drug candidates in its pipeline.

“I think, probably obviously, one of the jobs Chris will do is look at where we should prioritise, because he talks a lot about focus and focus areas, and sometimes maybe 35 is a lot for a company of our size.”

While The Ipha focuses on what it calls “innovative” medicines (new drugs), O’Connell is in an interesting position, given Biogen is also a significant player in biosimilars, with drugs challenging two of the early giants of the new-age biologics – anti-inflammatory drugs Humira and Enbrel.

When you’re in this role and when you’re in the Biogen role, there are lots of demands on you on a daily basis, so family are very important to me

—  Michael O'Connell

So what does he make of the current spike in medicines shortages and the suggestion that price is one of the reasons behind the problems this winter?

The Ipha boss is more persuaded by the sheer scale of the spike in demand – up to four times the levels at the peak of Covid, he says – and a general tightening of suppliers over recent years.

“I’m not sure there’s any evidence to suggest, you know, from a local perspective, that the changes to the cost of these medicines is the reason there was a shortage. A lot of it has to do with supply and demand at the time.”

‘Positive signs’

If Leqembi gets the nod, O’Connell’s life is likely to become even busier than it already is. Meantime, he cherishes the opportunity to escape the hustle and bustle of corporate life at his home in rural north Cork, where “you’re just Michael” playing golf with friends for a couple of euro at the weekend, standing on the touchline as team medic at junior hurling or intermediate football matches, or minding his recently born grandson, Jamie.

“Jamie’s our new lease of life, and it’s great. When you’re in this role and when you’re in the Biogen role, there are lots of demands on you on a daily basis, so family are very important to me.”

As for Leqembi: “Let’s see what the future brings. Alzheimer’s is a really difficult area and we are learning all the time. Hopefully, from a patient perspective, there’s positive signs ahead. But let’s wait and watch that process.”