Jeremy Drummond, senior vice president of Business Development at MedPharm, on the challenges and opportunities of topical delivery
Tell us about your background and the history of the company
Over the last 20 years MedPharm has focused on helping clients navigate the complex route to successful development of their pharmaceutical product. The company provides contract topical and transdermal formulation development and manufacturing services, specialising in dermatological, nail, eye, airway, mucosal membrane and transdermal product development. Our aim is to ensure that clients establish a data package regulators and investors can trust.
From its roots at King’s College London, MedPharm has grown into a thriving organisation with facilities in Guildford, UK, and Durham, North Carolina, USA, employing over 130 people. The company has supported clients across the globe, in the US, Europe, Australia, Japan, India, South Korea, the Middle East and China.
How do you work with pharma clients?
MedPharm’s service is customised to the needs of each client and their product. We work hard to understand the overall picture of what a client needs and then supply a detailed proposal outlining a recommended approach for the development of that specific product.
Typically, the business arrangement is ‘fee-for-service’. MedPharm also operates an FTE (Full Time Equivalent) business model for additional felxibility. The company has had direct involvement in the development of over 55 products currently on the US or European markets. MedPharm has also developed its own patented dermal drug delivery technology (MedSpray).
What are the advantages and disadvantages of using topical delivery for drugs? Why should companies consider this?
Topical delivery enables a therapeutic active to be delivered directly to the site of action, avoiding potential complications from systemic delivery. In the case of topical buccal or nasal delivery, it can also be used for rapid delivery to the bloodstream.
The key targets for topical delivery are diseases typically associated with skin, nail, eye, ear, airways (lung and nasal) and mucosal membranes. These diseases, many of which have unmet medical needs, often have pathways related to other established diseases (eg inflammation) and established oral drugs can be repurposed for topical use.
When developing a topical drug, it is essential that it is done in parallel with in vitro performance testing to demonstrate the release of the active pharmaceutical ingredient from the formulation and permeation and penetration of the drug into the relevant human tissue. Studies have shown that human skin is very different from that of animals used in classic models and so this approach provides the most realistic read-out of how a topical drug product is going to behave in the clinical environment.
One challenge, particularly for biologics, is that the skin and stratum corneum is designed to be an effective barrier. Most commercial dermatological pharmaceutical APIs have a molecular weight below 500 Daltons. There have been recent cases where we have been able to demonstrate the permeation and penetration, and importantly therapeutic activity, of a compound (in this case an aptamer) with a molecular weight of around 20,000 Daltons.
What are currently some of the challenges of working in topical medicine?
Clinical trials, not just for topical products, remain time-consuming, expensive and risky. MedPharm’s focus is to develop commercially viable topical formulations which are optimised in parallel with physical and chemical stability and aesthetics where the permeation and penetration of the drug into human skin central is to the process. More recently advances in the industry have seen the development of new in vitro models that also give a read-out of the activity of the drug on disease relevant pathways in the target human tissue. The data from these models, with the appropriate level of validation, is trusted by investors financing clinical trials and the regulators authorising them.
Regulators on both sides of the Atlantic have recognised that the necessity to demonstrate therapeutic bioequivalence in the clinic is often a major barrier to generic topical product introduction within all but the largest markets. The variability in skin adds inherent risks to any clinical trial on top of the expense. As the skin also responds to most excipients there is no true placebo, just vehicle components that are accepted to have some effect. This makes primary endpoints more difficult to meet, further increasing the risk of failure.
This creates a challenge for governments wanting to promote the introduction of topically applied generics as a way of reducing their healthcare bills, whilst at the same time being clearly obligated to register generic products without any additional risk to patients.
Regulatory authorities are now realising that the use of in vitro models can be used to cost-effectively demonstrate bioequivalence in human tissue. CROs are constantly developing and evolving with the aim to achieve a generic approval for a client without the inclusion of data from a bioequivalence clinical trial and supported by in vitro models to the appropriate level of validation.
What are the biggest opportunities?
The number of companies looking to develop products for topical delivery is definitely growing. It is a key target for repositioned drugs as new molecular biology discoveries demonstrate the crossover in key pathways associated with different diseases. The demand for solutions for orphan diseases associated with the skin and eyes is also driving demand for topical formulation development services.
A number of higher value dermatology products will come off patent in the years ahead including Taclonex (betamethasone and calcipotriene), Picato (ingenol mebutate) and Elidel (pimecrolimus). This, combined with regulators starting to accept bioequivalence on the basis of data from in vitro models using human tissue, has encouraged a number of high-profile generics companies to develop new products in the dermatology sector.
Pharmaceutical companies, of all sizes, recognise the inherent risks in topical formulation development and increasingly appreciate how topical delivery, coupled with in depth experience can de-risk their development plans and help them to attract investors when they seek funding.
Some in the industry are looking to differentiate established products to add new patient benefits, including the potential for the long-term control typically found with a transdermal patch without the associated inconvenience and potential sensitivity.
What are your hopes and plans for the future of the company?
The future remains very bright for MedPharm. There is a strong pipeline of new customers and projects, and the company is expanding its ability to provide larger scale clinical manufacturing services and, in the future, commercial supply.
A key growth driver is MedPharm’s ability to provide cost- effective solutions for the development of generic topical products, and many OTC pharmaceuticals companies are appreciating the development of custom models that help substantiate and promote new marketing claims for their products.