It is easy to get the impression that the quest for advanced multiple sclerosis treatments, and eventually a cure, is on cruise control.
Ali-Frederic Ben-Amor, Vice President, Global Medical Affairs for Neurology & Immunology, Merck
Breakthrough after breakthrough have brought astonishing benefits to the more than 700,000 people in Europe impacted by the degenerative disorder.
But researchers are refusing to slow down despite 20 years of high-speed discovery that has taken the field from symptom management to life-enhancing treatments.
The biology of multiple sclerosis, with its insidious and unpredictable attacks on the brain’s myelin sheath, is yet to yield its full secrets but scientists are chipping away its defences to create more effective and patient-friendly therapies.
Ali-Frederic Ben-Amor, Vice President, Global Medical Affairs for Neurology & Immunology, Merck, epitomises the field’s passion and refusal to take a backward step.
A year ago the company won EC approval for MAVENCLAD, a course of just 20 tablets that tames the body’s immune response system and can be taken on ten consecutive days at the start of two separate years to control the disease for four years.
Great progress
Significantly, it frees patients with highly-active relapsing and remitting MS from the burden of daily medication regimes which blight their lives.
But Ben-Amor, and teams across the pharmaceutical industry, are not resting on that or other triumphs.
“We are in a golden era for most of the patients but not for all,” he says. “Unfortunately, there is still lots to be done, particularly for the patients who have progressive forms of MS where there is a high unmet need.
“We have made great progress but we must remember that we do not have a cure and cannot address all the different phenotypes of the disease.
“I am very proud of what has been achieved because it has transformed the landscape. Merck and all the other players in the field are very proud of that.
“But we are not finished yet. We are still very motivated.”
The MS market has become a bustling environment with companies striving for extra efficacy for a disease that has a 2.5 to 1 female to male profile and normally strikes at child-bearing age and when patients are in the prime of life.
Merck is convinced that MAVENCLAD provides a huge step change for patients. Its trials demonstrated that patients achieved 50% fewer relapses and fewer new areas of MS activity and it currently has market authorisation in 39 countries.
Invest in more research
“Most of the MS patients are young women and one important consideration for patients is to be able to plan for pregnancy. MAVENCLAD offers lasting control of the disease allowing them to plan for pregnancy once the treatment course is completed. Like other DMDs, metal exposure should be avoided,” adds Ben- Amor, who has been involved in MS research and business operations for 20 years. “This is very important for patients because they want to have a life, to have families and plan the lives they want. “In patients who respond well to the treatment, we are practically stopping the disease. The issue is that not all patients respond as well as we would like and therefore it’s important for us to continue to invest in more research.
“The very important aspect is that the earlier you intervene in the disease, the better the chances of protecting what is still available. One of the great advances in MS over the last 20 years has been our ability to diagnose and start treatment earlier.
“In the absence of a cure, the name of the game is to start as early as possible, when the disease has very little impact to the brain, and prevent it from progressing as much as we can.”
MAVENCLAD’S short-course oral therapy profile is a bonus to a condition freighted with psychological drag-weights. Its debilitating impact on young people means that adherence rates are an issue and multiple companies are striving to provide treatments that both have results and do not derail daily activities.
Formidable foe
“With Rebif (interferon beta-1a), Merck’s legacy MS therapy approved in Europe 20 years ago, one of the innovations is the ability to have auto-injectors and devices that are very user-friendly. This will help us monitor adherence because, as with any chronic disease, long-term adherence and compliance to treatment is somewhat challenging, so we have been trying to develop solutions that are really patient oriented,” adds Ben-Amor.
“The dosage is tailored to a patient’s weight and you take a total of 20 days of treatment – the first week of the first month, repeated the following month and then again the following year – and over four years you will have a very high chance of being disease free. Convenience is very important to the patient and the physician.” But MS biology remains a formidable foe.
“The major challenge is to better understand the underlying biology of multiple sclerosis and we have been working very hard on that,” says Ben-Amor. “There are different aspects to that; one is understanding the biology and the other is understanding the patient needs.
“A cure is a very difficult target because we do not understand why the disease starts. We understand that some patients have a higher risk and there might be triggers, but it is very difficult to understand. The best example of the challenge is that if you take twins and one develops MS, the other only has 30% chance of developing
MS, even thought they have the same genetic background. There are environmental factors, such as viruses possibly, at play. It is a very difficult journey but we are working very hard to crack it.”
Working together
Hundreds of trials are bustling through clinical lines to decode the main strands of MS: relapsing and remitting, which affects around 80% of patients; secondary progressive, an advanced stage of the disease where disability accelerates; and primary progressive where patients start with an aggressive version that often leaves them in need of a wheelchair or other support after just five years.
Route to authorisation
Roche has developed Ocrelizumab, an infusion to treat relapsing MS and become the first treatment for primary progressive MS – although it was recently refused a licence in primary progressive MS by NICE, the UK government’s medicines regulatory authority.
Novartis has announced positive phase III trial data for siponimod, a drug for secondary progressive MS, which reduced the risk of a patient’s disability worsening by 21% after three months and 26% after six months versus placebo.
All will be fighting for reimbursement across a squeezed financial landscape so good trial data alone may not be a clear route to authorisation.
But the battle to beat MS continues at pace with the tantalising prospect that wins in the lab could also be translated to treatments for other neurological areas such as Parkinson’s or Alzheimer’s.
“MS is one of the few neurological conditions where you have the ability to slow down or modify the effects of the disease instead of offering just symptomatic treatment,” adds Ben-Amor. “I think what the industry has achieved recently does not get enough recognition. It’s like water from the tap, once you have it you don’t think how wonderful it is.
“But we are acutely aware of the work that still needs to be done. There is no cure for MS but we are getting closer.”
Danny Buckland is a health journalist