With a successful phase II trial behind it, BioCryst Pharmaceutical is now hoping to partner its gout treatment BCX-4208 to push the drug through pivotal trials and filing. The Alabama group is positioning the therapy, that inhibits the development of uric acid, as an add-on to standard first-line treatment allopurinol.
The company is targeting patients who do not achieve target uric acid levels on allopurinol alone, representing at least half of the 18 million gout sufferers in the US, Europe and Japan, BioCryst chief executive Jon Stonehouse says, speaking to EP Vantage at the American College of Rheumatology scientific sessions. With growing prevalence of gout and a standard treatment that has been showing waning effectiveness, Mr Stonehouse believes BCX-4208 will fill an important niche in the market (Therapeutic focus - Gout pipeline looks thin but holds promise, May 26, 2011). “Take this evidence of a growing population and really crummy choices in terms of what your treatment options are - for nearly half a century there was nothing - it creates a great opportunity,” Mr Stonehouse says.
New options explored
The past three years have seen an uptick of activity in new therapeutic options for gout. In 2009 the FDA approved Takeda’s Uloric, which as a xanthine oxidase inhibitor like allopurinol works on a similar mechanism of action. This was followed in 2010 by Savient Pharmaceuticals’ Krystexxa, a treatment for patients refractory to allopurinol or Uloric (Savient needs to deliver partner sooner rather than later. September 15, 2010).
Novartis’ Ilaris, a treatment for the orphan indication cryopyrin-associated periodic syndrome (CAPS), fell at the last hurdle as a treatment for gout flares (Ilaris sucumbs to its fate with FDA gout rejection, August 30, 2011).
There are two candidates in development ahead of BCX-4208, including Regeneron’s Arcalyst, a CAPS treatment that was recently filed in the US for approval in gout flares, and FYX-051 from Fuji Yakuhin and Suzuken Group, another xanthine oxidase inhibitor. BioCryst appears to be neck and neck with Ardea Biosciences’ RDEA594, which also presented phase II data at the ACR meeting but has yet to enter phase III.
With a growing population and many patients not reaching the recommended serum uric acid target of 6mg per decilitre, Mr Stonehouse believes there is plenty of unmet need that can be addressed by multiple agents.
“We don’t believe it’s a winner takes all market,” he says. “We think there’s plenty of room and doctors need choices."
A benign side effect profile and relatively low doses may help BCX-4208 in the marketplace, however. Ardea’s RDEA594 is a uricosuric agent, a class of drugs that has well-known drug interactions, including analgesics and sulfonylureas, and which are contraindicated in patients with kidney stones. Given that many gout patients have multiple health problems, Mr Stonehouse believes that BCX-4208 may be used in a wider population because it will have fewer side effects.
“You can go to higher doses with allopurinol but nobody does because they’re afraid of the side effects,” he says. “This is where this idea of combining our drug and allopurinol at a lower dose makes complete sense. You get better efficacy than the two separately, so it’s a synergistic effect, not an additive effect. And by using low doses of each drug you don’t see the side effects that you’d see at higher doses which for a chronic disease is critically important.
“That to me is the low-hanging fruit,” he says.
Positive early data
As a late-breaker at ACR, BioCryst presented 12-week data from its phase IIb trial in 278 gout patients failing to achieve the 6mg/dL goal. Patients taking 5mg, 20mg and 40mg a day of BCX-4208 in addition to 300mg a day of allopurinol achieved the goal in 45%, 39% and 49% of cases, significantly more than the 18% of patients taking a placebo in addition to allopurinol. A third group taking 10mg a day achieved goal in 33% of cases, which did not achieve significance compared to placebo.
Six month data will be available early next year, Mr Stonehouse says, which will provide a longer view of BCX-4208’s promise for potential partners. The goal is to bring on a partner by the second half of 2012 when phase III trials would ideally start.
That would be a propitious time for a partner to come in. BioCryst had a cash pile of $61m at September 30, with a forecast net cash use of $35m in 2011. Whilst R&D costs for BCX-4208 will be winding down, a partner will help fill the company’s coffers to fund clinical work for other pipeline candidates, including hereditary angioedema (HAE) drug BCX4161 and a hepatitis C antiviral, BCX5191.
Of those potential partners, Mr Stonehouse says the company is hoping for a straight outlicensing deal as it does not see the opportunity to add value by engaging in co-promotion.
For now, analysts are forecasting sales of $30m in 2016 following a 2015 launch, according to EvaluatePharma’s consensus.
The company's shares have been largely unmoved by the prospect of key clinical data, losing 45% of their value so far this year to give the company a market value of $131m. Release of the late-breaking data Tuesday resulted in a one-day 5% boost to $3.08, suggesting a very strong read out is required of the six month data to generate excitement.