Exploiting improvements in bioavailability, the Canadian company has developed unique oral film technology to help drugmakers secure exclusivity and financial returns
Photo as seen on IntelGenx website
Today’s pharmaceutical industry is becoming a crowded, patent-centric marketplace, and in this landscape drugmakers are looking for new technology to help them extend the life of their brand. For Horst Zerbe, CEO of Canadian company InteGenx, oral films can be a trick up their sleeve: the novel drug delivery technology not only improves bioavailability but also secures exclusivity alongside financial benefits.
The intent of oral films is to make a drug available for oral absorption via buccal or sublingual absorption. Zerbe explains that this method avoids “first-pass metabolisation” in the liver, increasing bioavailability of the drug and potentially reducing adverse effects.
Films not only offer advantages over conventional tablets because they can improve bioavailability, they are also easier to administer. This provides particular advantages to patients with special needs, like elderly patients, small children, or patients who have difficulties swallowing tablets.
Based in Quebec, IntelGenx develops and manufactures oral film products for treating a range of medical conditions using the VersaFilm platform to integrate drugs into the films. In its pipeline, there are drugs for pain, neurodegenerative brain diseases, migraines, erectile dysfunction, opioid dependence, hypertension, and schizophrenia.
“All VersaFilm products are typically manufactured using so-called coating equipment, meaning the drug is being dissolved together with film-forming agents and other ingredients,” Zerbe explains. “The solution is then spread (coated) onto a carrier substrate, dried, and cut into pieces of suitable size.”
Though there is huge flexibility in the type of active that can be used with this technology, the main limiting factor is the amount to be incorporated into a single film. A typical upper limit is about 50 mg/film.
Avoiding “first-pass metabolism” in the liver increases bioavailability and potentially reduces adverse effects
Currently, IntelGenx is working on or producing 11 different films. Most of these are in partnership with other companies, but Montelukast is the exception. In tablet form, this drug is used to prevent and treat symptoms of asthma and seasonal or year-round allergies.
Certain psychiatric side-effects derived from the drug have led people to seriously consider the neuroprotective aspects. Research then showed that Montelukast could rejuvenate aged brains in animals, suggesting that the leukotriene receptor antagonist may have a similar effect in humans.
A huge barrier to the effectiveness of Montelukast for human use is entering the bloodstream, then crossing the blood-brain barrier. Montelukast does the latter very poorly as a tablet, however, it has been shown to do this easily and in significant quantities when administered as an oral film.
Of the 11 drugs known to be in development by IntelGenx, four specifically target issues connected to the brain. The increase in bioavailability in this area of the body is particularly striking and may be the reason such a high proportion of drugs for the brain are utilising this delivery form.
Photo as seen on IntelGenx website
IntelGenx is in the clinical stage of integrating Montelukast into an oral film with encouraging results showing the ability to restore learning and memory in vivo.
Alzheimer's disease currently has very few treatment options, with none treating the underlying pathophysiology. Therefore, any advancements in this field are important, and the fact that Montelukast is disease-modifying would be of huge significance.
If oral films as a method to increase bioavailability was used for other drugs, there may be more accounts like this, saving drug development from failure or existing drugs that gain a new use.
The original intent of oral films was to increase bioavailability. However, the pharmaceutical industry quickly discovered another benefit to the technology.
Once a drug substance patent expires, generic versions of the original brand product will enter the market and kill the sales of the brand. By reformulating the molecule into a film product and obtaining patent protection for that newly formulated film product, the brand company can extend the life of the franchise. This commonly applied technique is often called “lifecycle management”.
By reformulating into a film and obtaining patent protection, brand owners can legitimately extend the life of the franchise
Using a contract manufacturer for these specialist delivery forms is an increasingly popular strategy. Zerbe says that commercial deals are usually structured such that partners are granted exclusive rights to market and sell products in exchange for potential upfront and milestone payments, together with a share of partner’s net profits or a royalty on net sales.
Milestones would typically consist of FDA submission and approval, commercial launch, and sales targets. “Profit shares would typically be between 25–40% of net profits,” he says. Specifically for IntelGenx, the company also retains manufacturing rights for its film products.
There are not many sectors more crowded these days than cannabis. IntelGenx has two deals ongoing for these type of products. One is with Tilray for a medical cannabinoid that has completed manufacturing scale-up and will launch in 2020. The other is with Tetra BioPharma for a pain-focused dronabinol drug that is already available outside the US and Canada.
In this market, regulatory issues can be a major barrier with this controversial compound. Zerbe explains: “It has been very difficult to keep up with the rapidly evolving and changing legal landscape surrounding edible cannabis products. In order to be able to keep up, we have involved an Ottawa-based consulting firm that specialises in cannabis legislation and the various application procedures.”
In spite of these regulatory complications, oral films are a smart way to differentiate and improve a product in an oversaturated market.
Whether for crowded markets or drugs with low bioavailability, oral films are an exciting innovation showing potential to provide a win-win for patients and businesses alike.