Targeting rare, or underserved conditions, where the potential exists for disruptive innovation has long been a successful inside track strategy for the biopharma sector. A person doesn’t have to look any further than the niche market for a drug like Sabril® (vigabatrin), approved for human use by the FDA in 2009, as well as during the late 1980’s in the EU for treating infantile spasms and refractory complex partial seizures. Sanofi’s (NYSE: SNY) Sabril, the North American rights to which have been out-licensed to Lundbeck (OTC: HLUYY), raked in $120 million last year, and saw a 35 percent appreciation in revenues when compared with 2013.
And yet Sabril’s NCE (New Chemical Entity) exclusivity has expired and its orphan drug exclusivity expires in August of next year, opening the door wide to innovators like Catalyst Pharmaceuticals (NASDAQ: CPRX). Catalyst has a vast amount of experience with its own version of vigabatrin (gamma-vinyl-GABA), CPP-109, and is rapidly developing an improved antiepileptic indication known as CPP-115. CPP-115 acts to inhibit GABA-aminotransferase (GABA-AT), much like vigabatrin, but has also shown itself to be some 200 times more potent when tested via both in-vitro and animal model, where its use resulted in much higher levels of the primary inhibitory neurotransmitter, gamma-aminobutyric acid (GABA). Given that some 30 percent of the 3 million Americans who either experience an unprovoked seizure each year, or who are diagnosed with epilepsy, find themselves wracked with seizures despite the best modern medicines and surgical techniques, a powerful antiepileptic like CPP-115 could be a real godsend.
Catalyst’s decision to strike while the iron is hot and develop a generic version of Sabril, given that that there are no listed patents and the company believes its processes do not infringe on any unexpired patents, is a shrewd move that sets up CPP-115 for more widespread adoption across its potential indication spectrum. Already granted orphan drug designation by the FDA for infantile spasms, as well as orphan medicinal product designation in the EU for a severe form of epilepsy involving infantile spasms known as West Syndrome, CPP-115 is also being developed for other neurological conditions associated with reduced levels of neuronal excitability regulator GABA, such as PTSD, and Tourette’s syndrome (TS). CDC estimates put the number of TS patients each year in the U.S. alone at somewhere north of 138,000 and PTSD, once understood as only a battlefield-induced ailment, is now thought to impair as much as 7.8 percent of all Americans at some point in their lives. What all of this really means is that the upside for an effective broad-spectrum antiepileptic treatment, without the side effects typical of the current standards of care, could be considerable.
In fact, CPRX reported top-line results just this June for an open-label, proof-of-concept trial of CPP-109 in treatment-refractory TS patients, where one quarter of those taking CPP-109 exhibited a clinically significant reduction in tics. The company’s massive, established body of clinical trial vision safety data from previous work with vigabatrin, including a 2007 bioequivalence study of its formulation against the European equivalent of Sabril, places CPRX out in a leadership position here to develop a generic, and should help the company nail the FDA and institutional review board bioequivalence study. CPP-115 may address one of the primary concerns with chronic use of vigabatrin, visual field defects, and the significantly enhanced potency also means CPP-115 could be administered using methods and dosages that could potentially make a world of difference for patients. Moreover, the development of CPP-115, for which the less-potent, riskier vigabatrin analog CPP-109 is currently acting as a kind of temporary research surrogate (to demonstrate the efficacy of GABA-AT blockade), aligns nicely with CPRX’s overall vision of developing novel treatments for a variety of rare neurological and neuromuscular conditions.
After all, Catalyst’s main focus is on its flagship candidate, a neuronal potassium channel blocker known as Firdapse®, for which the company recently initiated a rolling NDA submission to the FDA. Firdapse has already been granted orphan drug designation and breakthrough therapy designation for treating the rare muscle weakening autoimmune disorder commonly associated with SCLC (small-cell lung cancer), known as LEMS (Lambert-Eaton myasthenic syndrome), as well as a group of muscle weakness conditions known as CMS (congenital myasthenic syndromes), and the most common form of central vestibular nystagmus (involuntary eye movement), downbeat nystagmus. Firdapse has been marketed in the EU since 2010 for LEMS and has been put forth by the European Academy of Neurology as well, as a frontline symptomatic treatment for this potentially severely disabling disease.
Originally in-licensed for North America via a strategic collaboration with BioMarin Pharmaceuticals, which has CPRX spearheading the clinical development, Firdapse’s main target is treating the roughly 3,000 patients each year who are stricken with LEMS, half of whom have cancer – most predominantly SCLC, of which there are around 33,180 cases each year according to the American Cancer Society’s 2015 estimates. Firdapse has shown statistically significant improvements for a whole host of independent neurological functions in LEMS patients across numerous randomized, double-blind, placebo-controlled studies, as well as in one double-blind study with an active comparator. Recently having completed pivotal Phase 3 safety and efficacy clinical trialing via a multicenter, double-blind, placebo-controlled, randomized discontinuation trial that yielded positive top-line results (followed by an open-label extension period), Firdapse has also been made available by CPRX on a compassionate use basis under an Expanded Access Program in the interim preceding FDA approval, where it provides treatment to seriously ill patients for whom no other treatments are available.
Moving forward, CPRX remains squarely focused on the Firdapse NDA, while also pursuing CPP-115 as a candidate for future treatment refractory TS trials, and the company looks to be on track for approval of Firdapse sometime next year. Firdapse represents a distinct alternative to other attempts at managing the symptoms of LEMS, including monthly immunoglobulin IV infusions and medications like amifampridine capsules or corticosteroids, which are only marginally effective.
Substantial experience developing antiepileptic drugs and a rapidly advancing pipeline where its lead candidate is in Phase 3 are great signs of health for CPRX, which could be winding down the capital burn rate-intensive phase typical of development-stage biopharma companies within the very near future as Firdapse commercialization looms large on the horizon. Investors will want to keep a close eye on the company for news about its generic Sabril development and FDA approval of Firdapse.
Or, take a closer look right now by visiting www.catalystpharma.com