Last August, Pennsylvania-based Aprecia Pharmaceuticals made history when it won the first U.S. approval of a 3-D printed drug for its seizure medication Spritam.
Although Spritam’s active ingredient, levetiracetam, has been generic since 2008, Aprecia uses 3-D printing to create a highly porous pill which disintegrates on the tongue when taken with water.
Spritam was approved to treat partial onset, myoclonic, and generalized tonic-clonic seizures in people with epilepsy. As many as three million Americans have been diagnosed with epilepsy and some of the more elderly patients also suffer from dysphagia, or difficulty swallowing.
Aprecia hopes its improved formulation will boost adherence to the drug – a hurdle which has limited uptake of levetiracetam to some degree, despite its efficacy. In some clinical studies, levetiracetam has been shown to decrease the rate of seizures in epileptic patients by 50%.
And after opening the door for 3-D printed drugs, other drugmakers could look to follow Aprecia’s example and use the manufacturing technique for formulation improvements. For now, however, Aprecia’s CEO Ron Wetherhold believes the company is the only firm in the world that can manufacture a 3-D drug at commercial scale.
Dysphagia and formulation-design challenges
In essence, Aprecia combined their new formulation approach with 3D processing capabilities to create the orally disintegrating pill. As a result, Spritam can carry a higher dose-load of up to 1,000 mg. Their technology is protected by a wide array of patents, with patents on the manufacturing platform that extend out to 2033.
Despite leveciracetam’s efficacy, some patients with epilepsy have not been able to benefit from it. In general, patient noncompliance is a problem which stretches across many therapeutic categories.
For patients with epilepsy, the consequences of noncompliance can be severe. One survey found that 45% of epileptic patients who had missed a single dose of medication had experienced a seizure as a result.
The FDA has hosted hundreds of meetings in the past seeking to address noncompliance from a variety of angles. One recurring problem is the challenge presented by dysphagia, which affects an estimated 16.5 million people in the US (and possibly up to 40% of Americans according to the FDA). Dysphagia can make swallowing a pill particularly difficult.
In June 2015, the FDA issued a statement expressing concern about how formulation design decisions can make therapeutic pharmacologic treatment more difficult for patients with dysphagia: “We are concerned that differences in physical characteristics (e.g., size and shape of the tablet or capsule) may affect patient compliance and acceptability of medication regimens or could lead to medication errors.”
Added to more typical compliance hurdles, such as age, treatment side-effects, and co-morbidities, it becomes clear why patients find it challenging to maintain compliance.
This problem extends well beyond the central nervous system (CNS) therapeutic category, where Aprecia is currently focused. But Wetherhold explained the company’s thinking led them to focus on CNS: “As we explored potential applications for our 3D printing technology in prescription drug products, it was important that we identified disease areas with a real need for patient-friendly forms of medication.”
This decision was driven by analysis which found dissolving medications typically had success in CNS indications.
“Historically, 40% of the sales revenues achieved by fast-melt solid oral dosage formulation in the US were from products with CNS indications, which convinced us that physician-specialists in this therapeutic category saw potential value of such dosage forms from a medication-adherence improvement perspective,” Wetherhold said.
In January, Aprecia completed a $35 million preferred stock financing, led by Deerfield Management Company. The company plans to use the money to commercialize Aprecia, which became available at US pharmacies in March, and to further develop its pipeline, which includes three other CNS drugs. All three of the drugs remain in the early stages of development, however.
Aprecia aims to formulate the drugs using its 3-D printed dosing technology, targeting larger compounds with high-drug loads. Spirtam appears to leverage 3-D printing to improve dosing for these types of drugs, something which could prove useful in other settings. But it remains to be seen whether 3-D printed drugs will be adopted by larger pharmaceutical companies or the industry as a whole.