For years it seems the pharma industry has been an easy target in the court of public opinion for the high price of drugs. Few acknowledge the industry’s development costs and the financial risks it takes to study new drugs. According to the most recent Tufts report, the estimated cost of bringing a new drug to market is now up to $2.5 Billion, with a capital B.
One major reason for the high cost is the high rate of failure. The FDA conservatively estimates 90% of drugs that the industry invests in are never even submitted for approval, usually because they fail to reach their target endpoints in clinical trials. So the few drugs that do make it through the pipeline have to make up for those loses in order to encourage continued innovation.
And of course it all trickles down to the consumers (i.e., patients), who stand to lose the most when fewer drugs at higher costs are brought to market to treat their conditions.
Why do all these drugs fail in clinical trials? It’s not a shortage of drug candidates. New actives are being discovered every day. It often comes down to one word: Bioavailability.
Bioavailability issues limit the potential of many active ingredients, causing high failure rates and inability to find that “sweet spot” to achieve an approvable safety/efficacy profile. At the risk of oversimplifying, when there’s insufficient bioavailability, high doses of active ingredient need to be given to achieve the target efficacy. As a result, there can be toxicity in the form of side effects, limiting the drug’s tolerability. When a drug’s bioavailability is optimized, its therapeutic dose can be reduced, reducing associated side effects.
The Biopharmaceutics Classification System (BCS) classifies drugs into four separate classes on the basis of solubility, permeability, and dissolution. BCS II drugs are drugs with high permeability, but low solubility; the bioavailability of these drugs is limited by their solvation rate. Currently, 70% of pipeline drugs, and even 30% of marketed drugs, fall into this category.
CURE’s technology is changing all of this.
We don’t develop new active ingredients. We unlock their full potential by improving their bioavailability. And we can do this for both existing and investigational drugs.
Our platform has the unique ability to design formulations that improve bioavailability and match a desired pharmacokinetic (PK) profile via a number of different delivery options: oral film, buccal, or sublingual. Each of these options offers advantages.
Oral drugs get metabolized through the GI; buccal drugs directly enter the bloodstream through the oral mucosa; sublingually, drugs get absorbed by tiny blood vessels under the tongue. All these routes of delivery translate to different PK profiles.
Example: aspirin was formulated using CUREfilm Oral to increase the speed of onset (Tmax – the time after administration of a drug when the maximum blood concentration is reached) and improve efficacy (Cmax – peak concentration of a drug achieved after dosing; and AUC – total drug exposure over time). Higher blood levels were achieved more rapidly and sustained for longer [see graph @ https://www.curepharmaceutical.com/technology/#data].
The implications are significant. In an ischemic event, every minute counts, so a short Tmax is the goal. And the ability to achieve sufficient plasma levels to prevent new clots from forming, is critical. Moreover in the event of a stroke or heart attack, a patient may be unresponsive and unable to swallow a pill. CUREfilm can address each of these challenges.
What’s more, CUREfilm can be adapted to address multiple PK objectives. For some drugs, we may not want to increase Cmax to avoid safety concerns, but we do want a greater AUC.
Other times the goal may be able to get the same AUC as an approved drug, but use a lower dose. The aspirin data demonstrate the feasibility of CUREfilm to achieve some of these objectives.
Finally, the use of buccal or sublingual CUREfilm bypasses the GI tract, which has two big advantages. First, if the drug isn’t metabolized in the GI and absorbed in the liver and gut wall, the drug activity isn’t reduced before it reaches the circulatory system. Second, it reduces GI side effects such as diarrhea, constipation and dyspepsia, which can change the safety/efficacy ratio so critical to staying within an acceptable therapeutic window.
The next generation of innovation in drug development is here. And it’s not all about novel ingredients. It’s about the best way for those ingredients to get delivered into the bloodstream. CURE is leading the way in that innovation. For more information, contact [email protected].