Approvable letter no distraction for Shire's ADHD drug

The UK firm has been issued the letter by the US Food and Drug Administration (FDA) for SPD465 (triple-bead mixed amphetamine salts), a formulation of mixed amphetamine salts designed to provide extended release treatment of up to 16 hours for ADHD in adults with a single daily dose. The active ingredient in the new oral stimulant is the same as in the company's market leading ADHD drug Adderall XR (mixed salts of a single-entity amphetamine product), which only lasts six to eight hours. An FDA approvable letter usually signifies a glitch in the filed drug's application or that the product isn't up scratch - but Shire was quick to dispel this assumption: "This is very typical in the history of all stimulants,"​ Cléa Rosenfeld of the Shire told in-PharmaTechnologist.com. "No stimulant-based ADHD drug has ever got straight approval from the FDA, so it's pretty routine." ​ The new product is formulated using patented Microtrol technology, based on the use of coated or uncoated 'multiparticulates' or beadlets that can be filled into capsules or compressed into tablets. These beads then release the therapeutic drug into the body at certain points, depending on pH. The same technology is used in the existing Adderall XR ADHD drug. Although unable to disclose any details regarding any specific gripes the FDA had with the extended-release formulation, Rosenfeld did say that in two to six months when the FDA finalises its verdict on the drug, it would benefit from the Hatch-Waxman Act (formally known as the Drug Price Competition and Patent Term Restoration Act) which confers three years' exclusivity on the US market. However, Rosenfeld also stressed the fact that SPD465 isn't really a main priority for the company right now, as its next generation ADHD drug Vyvanse (lisdexamfetamine dimesylate) has taken centre stage in its product line up. "As far as SPD465 is concerned, the market is quite relaxed regarding timing,"​ said Rosenfeld. "What we're really doing now is assessing how to position it in the market - SPD465 was developed far before Vyvanse, but it's still a very good product." ​ The perhaps slightly hazy plans for the product come as a result of the company's high hopes for the new candidate, Vyvanse, the first prodrug stimulant i.e. a drug that remains therapeutically inactive until metabolised in the body. Seen as a next generation drug with significant advantages over the existing Adderall product (and therefore a potential competitor for the new SPD465 extended release formulation), Vyvanse is presented as more consistent with a better efficacy and safety profile, and doesn't rely on the pH of each individual patient as Adderall does. Shire acquired full control of Vyvanse following the company's $2.6bn acquisition of New River Pharmaceuticals in February this year, in a bid to strengthen its position in the ADHD market and gain access to new potential products. "Right now our focus is on Vyvanse,"​ said Rosenfeld, "we already have paediatric approval and will be filing for use in adults imminently." ​ Whether this new kid on the block could mean the end of plans for SPD465 is yet to be seen, with Rosenfeld claiming it is "too soon to say, but it's a good drug"​. However, considering the company originally stated that its ultimate plans for Vyvanse include transitioning "the majority of patients from its current market leading product (Adderall XR) to the next generation prodrug ADHD product (Vyvanse)"​ the future for Adderall products could be seen as somewhat unsteady. Adderall XR is currently Shire's lead product, currently contributing 48 per cent of the company's revenues ($863.6m (€640.2m) in 2006). The formulation patent covering the product extends until 2018, however generic companies are already chomping at the bit, and Shire was locked in litigation with Barr Pharmaceuticals until a settlement last year which prevented Barr from marketing a generic version of the drug in the US until April 2009. Once generic products start entering the market, Shire's earnings could clearly be seriously affected. Understandably, the company is therefore investigating other potential products that will help protect it when the storm hits. The strategy for the company now focuses on drugs with long-term patent protection in its core therapeutic areas. As part of this re-focus, the company sold off its immediate-release formulation of Adderall, which had been open to generic competition since 2002, to Duramed for $63m in August last year. This strategy was also responsible for the company's acquisition of New River back in February, providing the company with its new flagship product.