In 2016, Aprecia Pharmaceuticals brought to market the first prescription drug approved by the U.S. Food and Drug Administration that is manufactured using three-dimensional (3D) printing technology: SPRITAM®, an epilepsy medication that rapidly dissolves in the mouth. Levetiracetam, the active ingredient, is not a new drug; it has been marketed as antiepileptic since 2000, originally patented by UCB Pharma (U.S. 6,107,492 A). So what makes SPRITAM different, and why is this difference important?
Previously, high doses of levetiracetam combined with inactive ingredients needed for storage and handling made the medication, a pill, large and difficult to swallow, resulting in poor patient adherence. In contrast, SPRITAM disintegrates in the patient’s mouth in a matter of seconds, making it easy to swallow and improving patient adherence. SPRITAM is formulated with Aprecia’s ZipDose® Technology, which uses a proprietary 3D printing process to produce a solid yet highly porous, water-soluble matrix that rapidly disintegrates with a small amount of liquid. Such porosity cannot be achieved using conventional compression methods, but comes from printing the drug layer by layer. According to Aprecia, the ZipDose Technology is the only formulation platform to date that can achieve high doses in a rapidly dispersible form. In other words, SPRITAM is revolutionary (and patentable) not because of the active ingredient, but because of the dosage form.
In addition to SPRITAM (U.S. 9,339,489 B2 and U.S. 9,669,009 B2), Aprecia holds patents for rapidly dispersible dosage forms of topiramate (U.S. 9,492,380 B2) and oxcarbazepine (U.S. 9,314,429 B2 and U.S. 9,616,018 B2), both also antiepileptics, showing what new 3D printed pharmaceuticals could be coming down the pipeline. Conceivably, Aprecia could continue to patent “old” drugs turned into “new” drugs using the ZipDose Technology. While this might seem like cheating, teaching old drugs new tricks is a hallmark of patents in the pharmaceutical industry, whether it’s for an extended release formula, a new method of use, or combining known drugs in a new way. Aprecia’s ability to use the ZipDose platform to update the dosage form of known compounds has several potential implications. First, the amount of time and money spent on research and development may be reduced compared with bringing a novel compound to market, while Aprecia may still obtain intellectual property protection for the updated dosage form of the compound. This may give Aprecia more resources to devote to developing their technology platform or other drugs, including non-3D printed drugs. Second, by making drugs more patient-friendly, patient outcomes may be improved. For example, evidence shows that patient adherence to taking medication as directed increases treatment success. Therefore, improving dosage formulations may be as important for advancing disease treatment as developing novel compounds.
So can other pharmaceutical companies start to bring 3D-printed drugs to market? According to Aprecia, the company has the rights to more than 50 patents related to pharmaceutical applications of 3D printing (many exclusively licensed from the Massachusetts Institute of Technology) and has filed patent applications to protect their manufacturing system through 2033. However, by continuing to develop and change their manufacturing system, Aprecia may continue to file new patents to protect their technology well beyond 2033. Therefore, unless able to license the technology, competitors will need to develop different manufacturing systems and methods to create different dosage formulations in order to bring their own 3D-printed pharmaceuticals to market. Often, competition inspires innovation. Just what will the future hold for 3D-printed pharmaceuticals?