In a nearly flawless example of strategic innovation, Pfizer (www.pfizer.com) leveraged its in-house knowledge of GABAergic pathways to create Lyrica as a follow up to Neurontin. As early as a year after launch of Neurontin, small investigator-led clinical studies suggested that GABA agonists, Neurontin in particular, have a clinical benefit in chronic pain states.
Additionally, monitoring off-label prescriptions of Neurontin (estimated to be up to 86% of all Neurontin prescriptions) revealed extensive use in a variety of pain indications with anecdotal clinical pain relief. Using this data, Pfizer designed Lyrica’s clinical trials to test for epilepsy, the original indication of Neurontin, as well as neuropathic pain. The bet paid off when Pfizer received FDA approval for use of Lyrica in peripheral neuropathic pain in diabetic patients in 2004.
By leveraging use of a predecessor drug combined with a strategically planned Phase III trial, Pfizer differentiated Lyrica as the go-to therapy for neuropathic pain. The company exploited the move to evidence-based medicine for its new indication and insulated itself from payer pressures to use soon-to-market gabapentin generics because Neurontin was never indicated for pain. Generic manufacturers of gabapentin are unable to prove efficacy equivalence in the absence of bankrolling their own trials, and are unlikely to do so.
Moreover, Lyrica enjoys both FDA-granted NME exclusivity and new compound and medical-use patents, thus allowing Pfizer to recapture long-term revenue streams from essentially the same drug. Lyrica is projected to reach blockbuster status by this year with sales of $1.1 billion.
Initiative 2—Identify a franchise of similar compounds to target related conditions.
Accumulated R&D knowledge of chemistries and biological pathways must be leveraged to create a family of similar drugs. Traditional reformulations involve using the same active moiety and extending exclusivity for merely three years.
R&D teams should develop similar, yet enhanced drugs from the appropriate drug class to exploit both FDA exclusivity and new patents. This approach allows the extension of franchise revenue streams for the maximum term (e.g., 20 years including development time).
For example, AstraZeneca’s (www.astrazeneca.com) once-daily Nexium is a single isomer version of Prilosec. Compared to Prilosec, Nexium has decreased hepatic metabolism and slower plasma clearance, resulting in improved plasma concentration and better acid suppression. Improved kinetics alone would have led to a me-too proton pump inhibitor (PPI) that would have fallen to generic competition and payer restrictions, as did TAP Pharmaceutical’s(www.tap.com) Prevacid did.
On the other hand, AstraZeneca differentiated Nexium in a crowded PPI class by performing clinical trials showing a faster response benefit in GERD in addition to healing of esophageal ulcers. Furthermore, AstraZeneca performed trials showing that Nexium also helps to reduce the risk of NSAID-associated gastric ulcers, a benefit established in previous smaller clinical trials. The combination of a similar but new molecular entity and a suite of strategically chosen indications allowed AstraZeneca to distinguish Nexium from what was considered a class effect.
As a result, AstraZeneca placed Nexium as the first-line choice among mostly similar compounds. Pricing Nexium favorably to Prilosec allowed the compound to capture $5.1 billion of the $14 billion 2006 U.S. PPI market that includes inexpensive generics.
Initiative 3—Maintain tight communication between commercial and R&D teams.
A cross-functional team composed of R&D and brand and marketing teams should accompany a successful compound throughout its life cycle, and continuously evaluate both therapeutic and economic potential of emerging molecules and indications. An early team approach significantly mitigates development risks associated with the launch of next-generation products.
The R&D team’s significant know-how about drug classes accumulated over time should translate into a suite of related compounds with known efficacy and safety data.
The commercial team’s responsibility should be to identify lucrative markets and create effective communications that can be used to strategically position promising new drugs for novel, yet related indications. The teams must be managed to effectively share information and make joint decisions as to the best way a particular franchise should expand.