Returning to the roots of biotech and orphan drugs
Synageva is a public company committed to invading unexplored therapeutic areas — aka, orphan diseases — while returning to biotech roots with its rDNA (ribosomal deoxyribonucleic acid)-based proteins for replacement therapy. It aspires to the kind of mission and model other orphan-drug companies like Alexion have championed successfully, yet it brings an exceptional amount of industry experience and practicality to the task. Underlying its development of lead product SBC-102 (rhLAL), an enzyme replacement therapy for Lysosomal acid lipase (LAL) deficiency, and others in the pipeline is a diverse team of industry veterans equipped for commercialization. The company’s protein expression and production platform, as well as royalties from Roche for an acquired HIV product, Fuzeon (enfuvirtide), bring in cash for Synageva. It has completed a Phase 1/2 extension study of SBC-102 in late onset LAL D and plans to follow with a double-blind placebo controlled trial next year.
WHAT’S AT STAKE
Companies have concentrated on developing therapeutics for a relatively few rare diseases where further development of the compound has big-market potential, as Tim Cote, longtime rare disease advocate and chief medical officer of NORD (National Organization for Rare Disorders), observed at an AAPS (American Association of Pharmaceutical Scientists) conference last May. Unfortunately, he noted, that leaves most rare diseases with no treatment options, now or in the foreseeable future. If companies lived up to the spirit more than the letter of the Orphan Drug Act, a different model would emerge — one based on orphan drugs for orphan diseases and rare conditions where the need remains unmet — because most companies developing orphan drugs have generally targeted only a relatively few rare conditions or indications, flocking around ones that have become popular for their potential to lead to large-market indications for the same drug. Actually, such a true or “ultra” orphan drug model has emerged, however imperfect in form, with successful companies such as Alexion (Soliris/PNH), and Genzyme (e.g. Cerezyme/Gaucher Disease), as well as with new orphan drug developers, exemplified by Synageva BioPharma.
Let’s pause for a disclaimer: Pricing is the “fly in the ointment” for the “ultraorphan” model . All the company successes so far depend on the orphan blockbuster strategy; Gaucher prevalence is only about 1 in 75,000, but Cerezyme delivers around $800 million in sales per year with its price of $200,000 per patient. Synageva has not signaled a price for SBC-102 if approved, but the company’s presentation to analysts cites Cerezyme and other high-ticket orphans to indicate potential revenue. The same presentation, however, dramatically illustrates the human stakes as well — describing an infant with LAL Deficiency (LAL D ) surviving and growing well beyond the usual, dismal bounds of the disease after SBC-102 treatment. According to Synageva’s CEO, Sanj K. Patel, both the late and early onset forms of the disease are greatly under- or misdiagnosed, and the chief challenge in its drug development is finding the right patients for its clinical trials. Anticipating a similar challenge once on the market, the company built its clinical and commercial teams in tandem, beginning early on. Finding patients requires extensive outreach to specialists, academic centers, and opinion leaders, along with medical publications, conferencing, and encouragement of investigator-sponsored studies, especially as it gears up for a doubleblind placebo controlled trial in late onset LAL D. It is exceptional for a start-up to start out with the full complement of functions needed to reach those objectives. To whatever degree the company relies on high pricing to sustain its success, there is honor in its commitment to filling a truly unmet need. Synageva is not just developing drugs for rare conditions, but solitary hopes for patients with genuine orphan diseases.