Ordinarily, a medicine cannot be prescribed in the UK unless it has been given the appropriate marketing approval by the Medicines and Healthcare Products Regulatory Authority (MHRA) or the European Medicines Agency (EMA).
However, to take an innovative medicine to marketing approval can take up to 15 years, and can require total investment of over £1 billion. This is a risky proposition for a global pharmaceutical brand, but the risks and upfront costs can be prohibitive for small to mid-sized biotech businesses.
Given that many of the more innovative and promising medicines (and particularly those seeking to address rarer conditions) are currently being developed by small to medium sized enterprises (SMEs), such as relatively poorly funded university spin outs, regulatory barriers are not good news for patients, clinicians or the UK life sciences economy.
The Early Access to Medicines (EAM) Scheme
The EAM Scheme was introduced in April 2014 to provide an accelerated route to market for promising, innovative treatments which address an unmet clinical need. The EAM Scheme is primarily intended to benefit patients by allowing them, in limited circumstances, to access potentially life-enhancing / extending medicines earlier than they otherwise could. However, the EAM Scheme also provides opportunities for drug developers.
There are three stages to the EAM Scheme:
firstly, a medicine must be awarded 'promising innovative medicine' (PIM) status by the MHRA. A medicine will only be awarded PIM status where it is 'likely to demonstrate significant benefit for patients in life-threatening or seriously debilitating conditions';
secondly, the MHRA must issue a positive 'scientific opinion', based on data on the medicine’s quality, safety and efficacy; and
finally, the medicine may be prescribed, before it is submitted for full regulatory review (hopefully leading to marketing approval) and commissioning.
The EAM Scheme is good news for patients. However, biotech SMEs will need to weigh the risks versus the benefits of participation in the EAM Scheme. For the right manufacturer, with the right product aimed at the right patient group, the rewards of the EAM Scheme could be enormous.
The first, and to date only, medicine to receive a positive scientific opinion under the EAM Scheme is Merck’s melanoma treatment, pembrolizumab (Keytruda). While it is not surprising that the EAM Scheme pioneer was a well-funded global pharmaceutical giant, a key measure of the scheme’s success will be whether it helps small and medium biotech companies, as well as global pharmaceutical brands, to get their most innovative products to market.
Early indication of regulatory treatment
A manufacturer is able to apply for PIM status relatively early in a medicine’s lifecycle, long before it would normally have an opportunity to get any form of regulatory feedback on that medicine.
A medicine that is awarded PIM status will not necessarily go on to receive marketing approval. However, an early positive indication by the MHRA (a relatively strict regulator of a 'big 5' EU market), in the form of an award of PIM status, may lend credibility to the business case behind a particular medicine. This credibility could be an invaluable tool in attracting investment and marketing the drug to potential prescribers and payers.
The risk is that an ill-conceived application for PIM status could kill off the chances of an otherwise promising medicine at a very early stage. Just as a medicine that is awarded PIM status will not necessarily go on to receive marketing approval, a medicine that fails to receive PIM status will not necessarily fail to receive marketing approval once that drug and its accompanying data package has been developed further. However, there is a risk that investors will read too much into a failed PIM application.
Manufacturers should not, therefore, treat an application for PIM status as a 'dry run' for an application for marketing approval, to be used in every case. However, for certain promising, innovative medicines that address an unmet need, it may be a valuable way to support an already strong business case.
Early access to real-world evidence
Investors are understandably concerned to assess a medicine’s popularity with prescribers, as well as its safety and efficacy. Likewise, payers are under increasing pressure to justify spending decisions with reference to patient outcomes.
Clinical trials are a vital step on a medicine’s journey to marketing approval. However, the data that they generate can be unrepresentative, owing to the tightly-controlled nature of trials, and is often targeted very specifically at securing marketing approval by demonstrating a medicine’s safety and efficacy in accordance with the regulator’s strict data requirements.
Thus, while undeniably necessary, clinical trial data can be insufficient for making a medicine’s business case to investors, or insufficient for justifying a medicine’s cost to payers. Real-world patient data may be much more persuasive in both of these contexts. The EAM Scheme, which enables manufacturers to get a medicine to patients much earlier than would otherwise be possible, is ideally placed to generate this real-world data, which, coupled with clinical trial data, will give those manufacturers that take the plunge a potentially significant advantage.
Of course, as well as participating in the EAM Scheme, a manufacturer will still need to conduct clinical trials, invariably at great cost. Any expenses incurred through the EAM Scheme will therefore be in addition to the usual costs of taking a medicine to marketing approval.
The fees for participation in the EAM Scheme (obtaining both PIM status and a scientific opinion) are £33,027. Relative to the very high costs of drug development and regulatory approval, this is a fairly low figure. For example, the EMA’s fee for a marketing authorisation application starts at €278,200 (around £195,000).
More significantly, however, the EAM Scheme receives no Government funding. Consequently, where a medicine has received a positive scientific opinion, the manufacturer will be obliged to supply that medicine under the confines of the EAM Scheme to patients through the NHS, without any reimbursement.
The EAM Scheme does not, therefore, present an opportunity to secure instant profits. However, as part of a strategic approach to marketing an innovative medicine, it could be an invaluable tool for drug developers.