Dr Joy Duffen has been representing The Cure Parkinson’s Trust (CPT) on a number of important panels looking at improving the means by which we may bring new Parkinson's(PD) treatments forward. Having a clear regulatory and commissioning pathway is critical to enable potential new treatments for PD to be easily accessible to people living with the disease. Two significant bills we have been involved in are the The Off Patent Drugs Bill 2014-15 - now withdrawn and the Access to Medical Treatments (Innovation) Bill 2015-16 (previously the Medical Innovation Bill proposed by Lord Saatchi) – ongoing. Although in general support for these bills from AMRC members has been minimal the process of debate has been a very encouraging example of cross party co-operation and constructive thinking including a positive commitment from the Department of Health to not only consider legislation but also to pursue and facilitate non-legislative strategies making best use of current policies and organisations to try to ensure better access by patients to innovative treatments.

How do we get better drugs to patients?

Whilst the old and established medications that are favoured in the treatment of Parkinson’s might be expected to be amongst the armoury of any good consultant and probably familiar to and widely prescribed to patients, what about the more unusual, new or completely unheard of options?

CPT supports much innovative research notably focussing on projects that are very close to clinical translation i.e. could yield new treatments for patients within five years or even sooner. Often drug candidates have been used in other conditions and have a marketing authorisation (licence) issued by the regulatory authority for controlling the use of drugs in the UK - the MHRA (Medicines & Healthcare products Regulatory Agency). This means that they have been thoroughly evaluated in terms of the balance of risk and benefit to patients and they have a wealth of preclinical and clinical (human) data to back them up. In the UK most commonly prescribed drugs for PD are now off patent (i.e. are no longer the solely owned commercial product of the originating pharma company) and their cost is not a controversial issue.

As we drive the search for new and better treatments, however, notably those that have the potential to modify the disease course, the means of getting these treatments to patients becomes a more complex issue. CPT continues to try to keep in touch with and contribute to developments in the multiple potential routes for taking an exciting new drug candidate to patients in a safe yet expeditious route. With drugs that already have a licence for one indication but are found to have potential benefit in another (what we term 'repurposing'), there is the option for registered prescribers to give the drug “off label”, indeed prescribers have the legal power to prescribe any drug or treatment to patients whether it has a licence of not.

The most common use of “off label” prescribing is in paediatric medicines where approximately half of the commonly used drugs have never obtained a licence for specific use in the very young (or the very old!). This is largely related to the difficulty of conducting sufficient clinical trials in the specific age group. Nevertheless most of these drugs will have been thoroughly evaluated and have a long safety record of their use in their primary indication and gradually establish an acceptable track record in those of a different age group. Prescribers in these fields are generally comfortable with this level of off label use of such drugs but where the practice is less established more caution is applied. The guidance from the General Medical Council is very supportive of off label use but is clear that where there is a licensed alternative that drug should be the first to be considered.

So a licence is the most reassuring status for patients and prescribers but the development of a new drug from the stage of interesting chemicals in the lab to a product can take over 15 years and costs in excess of £1 billion. 

In the last few years there have been a number of schemes that try to address the frustrating barriers to innovation. In terms of new drugs the regulators have developed several routes that can streamline or make less onerous the process of obtaining a licence especially in the case of a drug that can claim to offer a breakthrough in treating a condition which is poorly served; a truly disease modifying treatment for PD could well fall into this category. There has been the establishment of strategic funding for clinical research notably through the National Institute for Health Research (NIHR ) which is due to receive £1billion of funding in 2016 according to George Freeman MP, (The Parliamentary Under-Secretary of State for Health). Orphan Drug Status can facilitate a quicker or smaller trial where a very low number of responders are investigated, generally because the disease is rare but certain subgroups of patients may also qualify i.e. those with a clear genetic predisposition the effects of which the drug is targeting. There is also an Early Access to Medicines scheme which can provide an early indication of potential success of a drug and can help to secure the funding for further development.

In the last couple of years at least two relevant private members bills have been of interest to CPT, notably the Medical Innovations Bill and The Off Patent Drugs Bill. There have been numerous consultative meetings including those instigated by the Department of Health’s Medicines Pharmacy & Industry Division -

to gather the key stakeholders together to talk this through and identify what further steps might be taken to support prescribers and patients.

A campaign of support especially for the off patent bill but more importantly for the requirement to find non-legislative solutions to the unequal access of patients to valuable off label drugs has been led by Breast Cancer Campaign and supported by CPT and notably AMRC members generally.

Currently the only remaining bill is the Access to Medical Treatments (Innovation) Bill which has just been through its reporting stage on January 29th 2016. The bill that proceeds concentrates on establishing a data base of relevant innovative practices that could help to inform those that need to access currently disparate information. For more information see: accesstomedicaltreatmentsinnovation.html

So…. how can we improve the consistency and adoption of new treatments that are yet to fulfil the gold standard of a new licence? All stakeholders agree that there are many things that can be done within the existing frameworks of legislation and commissioning. 

In the case of a licence the main problem is the lack of commercial incentive where the drug is off patent. Various potential solutions may emerge: the regulators are willing and able to offer more and better guidance to not for profit groups willing to undertake the complex and expensive process of obtaining a licence. Charities such as CPT or academic institutions may be able to support the conduct of definitive studies and possibly even pursue a licence directly, ideally supported by a group with the resources and experience to manage the manufacture, distribution, marketing and post marketing surveillance (following up on safe use in practice), interestingly the British Generic Manufacturers Association announced that they are keen to pilot a licensing programme for repurposed off-patent drugs by partnering with charities. They think they can do this without resulting in a huge increase in the price for the drugs concerned.

To support use through other routes proposals focussed around the better utilisation of current groups e.g. recommendation of research results from the NIHR, an MHRA review of safety and efficacy and/or a NICE update to its guidance or use of other review mechanisms. Emphasis is on providing sufficient information to prescribers for them to make a decision with their patients and a need for the drugs concerned to be subject to some sort of uniform financial support i.e. to avoid the need for an individual business case to be made to commissioning bodies each time the instance of use arises.

NICE and the BNF have already committed to greater collaboration and improved review procedures for off licence drugs and the GMC has raised off label prescribing as a “hot topic” - see more here: gmc-uk.org/guidance. The GMC's general prescribing guidance can be accessed here

A more general review of Innovation in the UK has been published by George Freeman MP led by Sir Hugh Taylor - “The Accelerated Access Review” - for the Department of Health on accelerated access to transformative drugs, devices and diagnostics for NHS patients. 

As an observer and contributor to many of the activities described above I must report that there is a huge sense of willingness of all concerned to facilitate the best outcome for patients and to involve them in everything that is relevant.

My greatest delight this year would be to see CPT in a positon to have to consider further how best to get some of its successful Linked Clinical Trial drug candidates to patients – what a great challenge to have for 2016!

Dr Joy Duffen - 2016