The benefits of drug reformulation

Stuart Madden, PHD, is Chief Scientific Officer at Neurelis, a neuroscience-based company that licenses, develops and commercializes product candidates for epilepsy and psychiatry, such as a diazepam nasal spray for epileptic seizures. Here Madden talks to us about the benefits of reformulating drugs to serve unmet medical needs.

Pharma IQ: Given how expensive and time-consuming drug development is, why aren’t more pharmaceutical companies focusing on drug reformulation?

Stuart Madden: It is usually health economics that relegate reformulation programs’ attractiveness. That can vary significantly dependent on the geographical region and what the public sector and private health insurance companies will pay for drugs that provide, at times, only a modest improvement over the current standard of care.

Conversely, new chemical entities (NCEs) serving an unmet clinical need or providing a significant improvement in treatment will always be priced at a premium to healthcare providers and offer an attractive financial return for companies willing to invest the time and money for their development.

The associated risk of NCE development failure due to poor safety and/or efficacy after investing significant costs over a lengthy development timeline are significant, compared to the reformulation of an existing drug that has a proven track record of therapeutic performance. However, the upside outweighs this risk financially.

Pharma IQ: What are some examples of drug reformulations that can improve patient outcomes? 

SM: There are numerous examples, a simple one would be switching from an immediate release tablet to an extended-release tablet. This would improve patient compliance, for example if the dosing regimen switches from twice daily to once daily. It would also improve therapeutic performance by smoothing the drug-plasma profile, avoiding drug concentration peaks that may be a safety concern, and minimizing drug concentration troughs (that may be below the minimum drug level needed for efficacy).

There are many examples of these types of reformulations and there are well established technologies for a whole range of specialized oral delivery systems that offer advantages, such as delayed release to avoid gastric absorption and oral disintegrating tablets that don’t require water.

Other examples are switches from parenteral (injection) that typically require administration by a healthcare provider to non-parenteral, such as transdermal, nasal and buccal. These can be self-administered and offer improved patient compliance and convenience. A specific example would be the recent introduction of diazepam nasal spray for acute repetitive seizures as an alternative to diazepam rectal gel.

Pharma IQ: From a business perspective, how does drug reformulation benefit pharma companies in terms of revenue? 

SM: If the innovator is doing the reformulation, it delivers the benefit of an improved product to the patient that provides a refresh for the brand and repositions it in the market as an improved product. There is also the potential for further exclusivity, either from a regulatory standpoint or from a patent perspective dependent on how innovative the reformulation is.

Relatively speaking, this is a cost-effective approach to extending the life of the product and delaying generic competition. For the non-innovator it is an opportunity to introduce a product into that marketplace that has an established safety and efficacy profile, avoiding the significant development outlay associated with the extensive preclinical and clinical testing that would be required for an NCE. It may also be seen as an improvement on the current standard of care, further enhancing its commercial attractiveness.

Pharma IQ: Do you think research into psychedelic drugs for instance, could encourage more pharma companies to reformulate products?

SM: I do not believe the current research into psychedelic drugs will have a significant impact on pharma in terms of reformulation. I believe this approach is already well embedded in the industry.

However, psychedelic drugs as a relatively new field in mainstream pharma will certainly benefit from the array of novel formulation approaches that are now available and have come about because of pharma looking at reformulation in general to improve drug delivery. The space is relatively new so it will be interesting to see how they approach treating specific indications in terms of dosage form design.

Pharma IQ: How do you see reformulation evolving in the next three to five years? 

SM: I see the development in specialized dosage forms and delivery systems continuing and these innovations leading to improved treatments. For example, improved bioavailability, better patient compliance through ease of use and more targeted drug delivery to the site of action. such as direct to a solid tumor, improving efficacy and safety.

These developments will benefit both existing drugs and newer drugs that will be coming off patent over this period.

Quick links

• Pharma IQ Live: Pharma Manufacturing Automation 2022
• How to drive efficiencies in manufacturing, with Procter & Gamble
• The challenges of handling and delivering highly potent oncology drugs

Get exclusive access to member-only articles, reports, videos, interviews, webinars and other premium content from industry experts and thought leaders by signing up to Pharma IQ here.