We are in an era of exciting breakthroughs in the treatment of rare diseases. There have been recent advances in treatment in diseases such as spinal muscular atrophy (SMA), Duchenne muscular dystrophy, ADA-SCID, sickle cell disease and Beta-thalassemia. Some are disease-modifying treatments (DMTs); others, gene therapies. Suddenly, patients have an opportunity to extend and maintain their quality of life when previously there was only symptomatic or palliative care.

When a new treatment or potential cure becomes available (in a trial or through special access programs or once launched), the disease landscape dynamics undergo a ‘sea change’. Through our market research across so many rare diseases where treatment is either upcoming or just launched, we have witnessed interesting behavior shifts and have grown an understanding of how to activate the patients.

  1. The arrival of a new DMT reactivates what may have been a ‘stagnant’ disease system. Any new breakthrough is long-heralded and anticipated. News has always traveled fast around any rare disease population – it may be a small world but it is a super-connected one, generally. Good or bad news is shared rapidly. This means that patients and caregivers are often very aware of forthcoming trials and new treatment options. They await them anxiously, wondering whether they will get a chance to try them out. Willingness to be in a trial can be high. There is a buzz around new developments that gets the rare disease community engaging with each other and their physicians.   

Prior to there being a treatment, patients may have chosen to disengage from the healthcare system over the years. If they know their diagnosis but there is no successful treatment, they may see no point in seeing a specialist that can only monitor their decline. Instead, they prefer to be in ‘denial’ and make the best of the life they have. This was the case in SMA before treatment arrived. Some patients continued seeing those who could help them such as physiotherapists but did not visit their neurologist any longer. From the physicians’ perspective, consultations where they can offer no effective treatment leave them feeling uncomfortable and disempowered as they cannot fulfil their role as a treater.

2. The arrival of a DMT places significant time pressure on those in the disease system because many breakthrough treatments may only be beneficial if given before the damage is done to the patient’s body. Suddenly, there is greater urgency to identify the disease early.

Typically, rare diseases are not diagnosed quickly – the convoluted path to diagnosis with its multiple specialist visits is a well-documented fact. Genetic testing can take a long time and expertise lies in a few centers – often it can be a matter of pot luck whether the patient reaches a center of excellence or not. The chances are higher if you live in a metropolis than if you live in a rural setting.

When a rare disease is more easily passed through the generations, individuals may suspect they have the condition but not necessarily want to know for certain. Huntington’s disease is a case in point. The diagnosis has long been a death sentence as no DMTs have existed, and often future patients are current caregivers watching the ravages of the disease on their loved ones. No surprise then that they may hesitate to check out their personal fate by being tested. Individuals may take years to make such a life-shattering decision. However, once a medical advance promises some hope then the resistance to being tested is reduced, though not eliminated.

The appearance of a DMT or gene therapy that is effective may also mean that newborn screening is more important. In SMA, for example, speed of diagnosis is largely determined by whether there is newborn screening available or not. The availability of this continues to be patchy from country to country and region to region, but now there is a real incentive for it to be done more routinely, as recent treatments need to be given while the baby is low weight/young. Delay may mean the opportunity to save quality of life is lost.

3. Knowledge of a new treatment alone does not result in immediate and unquestioning uptake of it. Many factors are weighed up. Many influences are involved.

For example, a parent being faced with the possibility of gene replacement therapy will weigh up the pros and cons very carefully. What will the child’s quality of life like be in the short term? In the long-term? Will they be infertile? Will they live longer? Will they live better but for less time? Is it morally right for the child themselves to decide? If so, when?

Not easy decisions to make and ones that require pacing, support, balanced and detailed information on the pros and cons, as well as multiple viewpoints.

Of course, the cost of breakthrough treatments may make access to them prohibitive in certain markets. Even in systems such as the UK where treatment is ‘free’, getting approval for extremely costly medication means jumping through many, many hoops. This requires a lot of effort from healthcare professionals and the patient/parent. I spoke to the father of a boy with Duchenne muscular dystrophy some years back as he explained the process by which he managed to access a treatment for his son. It was tortuous and needed repeating every 6 months. It is usual for one parent to give up work to champion their child’s cause and fight for much-needed treatment. It is a full-time job. But what of patients who don’t have that special advocate – and can’t advocate for themselves because they are too ill or young?   

4. As in any therapy area, some patients/caregivers will be more proactive than others, although typically in rare diseases more are ‘expert’ than the average. They often need to become assertive to get listened to and diagnosed. However, not all will push for better/the best. Not all will be connected in to support groups who can inform and influence them. In one rare disease, we saw parents on a trial were posting, on a Facebook group, video evidence of the drug’s efficacy (films of their child’s walking and writing) and other parents were using this to give them confidence to demand that their own neurologist prescribe the drug too. This is an example of how important an online forum can be in providing a platform for the more proactive parents to influence the less proactive.

5. Understanding how willing patients will be to take up the offer of a new treatment is vital for any pharma company planning a launch. Even within a very small population, we see patients and caregivers do not act in the same way or at the same speed to the arrival of a treatment. It is crucial to understand how the target for the treatment will sub-divide, profile those sub-groups and then understand what each needs to activate them to be open to the new treatment. Some who will be more knowledgeable, confident and activated will be self-motivated to seek out information and to raise the new drug in discussion with their physician. Others will be passive and assume that their physician will tell them all they need to know.

By profiling these patient types clinically, emotionally and psychologically, and then applying behavioral science it is possible to tease out what will activate each type or hold them back from demanding better treatment. 

Without activating the different types of patients/caregivers that make up the DMT candidates, there is a risk that they will miss out on the opportunity to have a better life and the disease system will remain stagnant. What we have learnt through listening to rare patient and caregiver voices is that new treatment brings hope and optimism where there has been none: nevertheless, there will be many hurdles to overcome.