Interview – Aprecia sees the future in three dimensions

The first drug produced using 3D printing, a formulation of the epilepsy therapy levetiracetam, was approved in the US in 2015. But its maker, Aprecia Pharmaceuticals, will no longer bring drugs to market singlehandedly. Instead it is licensing its drug-printing tech to other groups, and this offer has just been taken up by Cycle Pharmaceuticals for its orphan drugs.

“The company has transitioned its business approach and now we’re very much focusing on partnerships,” says Don Wetherhold, Aprecia’s chief executive. “We can refine or repurpose existing APIs for customers or perhaps maximise the innovation value of new therapeutics.”

The change in Aprecia’s strategy came as the group was bought by an affiliate of the generics maker Prasco Laboratories in September, though the licensing deal with Cycle had been gestating much longer than that. Prasco sees Aprecia as a way to expand its lifecycle management offering to the pharmaceutical industry, Mr Wetherhold says, though he claims that the two groups operate independently. 

Melt in the mouth

The levetiracetam formulation now called Spritam was hailed as a revolutionary therapy when it was launched in 2016. Produced using Aprecia’s ZipDose technology, the drug takes the form of a porous pill that rapidly dissolves when taken with with a sip of water. The tablets are produced at two US facilities that can print tens of thousands of units per hour.

The pills are then transported to pharmacies and dispensed as normal. For future orphan drugs it is possible that the patient would go to a speciality pharmacy that would order the pills to be printed on demand and delivered to the patient’s home, though the feasibility of this model has not yet been evaluated for regulatory approval.

The ability to print on demand is useful for drugs used by small numbers of patients, but it was not the principal attraction for Cycle. Instead it was two other aspects of ZipDose-formulated pills that hooked the UK group.

“This technology allows two things,” says Antonio Benedetti, chief executive of Cycle. “One is a fast-melting technology and the other is it allows loads of active ingredient.” Aprecia’s pills can deliver around 1,000mg of API apiece.

This ought to allow the two companies to develop new formulations of existing orphan drugs that ease the pill burden and address dysphagia. Mr Benedetti says fast-melting tablets work very well for people who have problems swallowing.

Development of the first formulation has begun, but Mr Benedetti declines to state what the molecule concerned is or what disease it will treat, beyond stating that it is an orphan condition.

The responsibilities of the two partners are clear, at least. Mr Wetherhold says Aprecia will do all the formulation work for the new product and Cycle will handle clinical development as well as regulatory filings globally. Then, if approved, the drug will be manufactured by Aprecia, with Cycle having commercialisation rights in select markets.

Clinical development and regulation of the new product, and those that will follow it, will be similar to the standard process for generic drugs, Mr Benedetti says, with some additional testing for bioavailability and dissolution profile. The requirements will depend to a large extent on the regulatory route – it is not yet clear whether Cycle’s drug will be submitted as an ANDA or 505(b)(2) application.

The project is expected to reach the market in two or three years.

Open for business

The agreement with Cycle is to be the first of many for Aprecia. It was a few years in the making, and started in a fairly ad-hoc manner when business development staff at both companies happened to meet at a conference and got chatting. In future Aprecia will be far more proactive in signing up new licensees.

“We recently had a big exhibit at the AAPS meeting in San Diego and that was really our first ‘coming out’, if you will, to the pharmaceutical community to let them know that were open to partnerships,” says Mr Wetherhold.

Before that Aprecia had been developing its own products with the idea that it would have a fairly standard speciality pharma model and market its own products, “but we feel like now is the time to evolve the technology, to advance it as quickly as possible, and the best way to do that is through partnerships”, he says.

This is perhaps connected to the fact that Spritam sales have been rather disappointing, despite the positive view taken by the FDA and payers. Regulation was reasonably easy, with Aprecia mainly having to prove that the production of Spritam could be done consistently at scale.

Spritam’s reimbursement was straightforward too, perhaps surprisingly so in a world where payers are often sceptical of new technologies, particularly for drugs with cheap generic equivalents like levetiracetam.

“Right now it’s only marketed in the US, and a pretty high percentage of the commercial plans cover Spritam,” Mr Wetherhold says. In some cases it requires prior authorisation from the doctor before an insurer will cover it, and Aprecia runs subsidy programmes to make sure the patient does not have to pay more than $10 out of pocket for a month’s prescription.

It is also covered under Medicare and Medicaid, though Mr Wetherhold says some states are stricter about prior authorisation than others. “But all in all coverage for what I would call a lifecycle management type of product giving the drug some enhanced convenience, I would say our coverage is very good.” It is priced in the mid-range for branded epilepsy drugs.

Still, “We didn’t have the take-off of the drug that we anticipated,” Mr Wetherhold says. The company is now relaunching Spritam in the US with the help of Prasco, whose affiliate bought a controlling interest in Aprecia in September.

The deal with Prasco will give Aprecia financial support as it seeks new licensing agreements. Once the new business model takes hold, and if Spritam’s relaunch is successful, Aprecia should be able to support itself.

To contact the writer of this story email Elizabeth Cairns in London at elizabethc@epvantage.com or follow @LizVantage on Twitter

Share This Article