BioCryst nods goalward to pharma partner, but M&A gets red card
This article was originally published in Scrip
BioCryst Pharmaceuticals believes it has a shot at the competitive gout market, based on positive Phase IIb data from the extension study for its novel oral drug ulodesine (BCX4208), but it needs a pharmaceutical partner to finish off the move.
BioCryst senior vice president and chief medical officer William Sheridan said a Phase III program for the purine nucleoside phosphorylase (PNP) inhibitor in combination with the standard gout treatment allopurinol will be too large and costly for the relatively small company, which is headquartered in Research Triangle Park, North Carolina.
But with longer-term Phase IIb data that confirms response rates (the primary endpoint) twice as high as placebo, BioCryst is preparing a Phase III development package so that ulodesine looks like a clear shot on goal for mid- to large-cap pharma players despite higher gout flare rates (a secondary endpoint) among ulodesine-treated patients.
BioCryst's stock price closed up only $0.06 at $4.42 per share on 24 July when it reported data from the extension study confirming earlier results, but the company's stock jumped by $0.58 to $5 per share in after-hours trading.
Some BioCryst competitors with drugs that reduce uric acid levels have been acquired by Big Pharma.
AstraZeneca paid $1.26 billion to acquire San Diego-based Ardea Biosciences, which has two selective inhibitors of URAT1 – the Phase III asset lesinurad and RDEA3170 in Phase I (scripintelligence.com, 23 April 2012).
Takeda completed its $800 million acquisition of URL Pharma in June and expects the company to add $564.1 million in net sales to its balance sheet (scripintelligence.com, 5 June 2012). URL Pharma's biggest asset is the gout drug Colcrys (colchicine).
But Dr Sheridan said BioCryst isn't interested in being acquire. The company wants to negotiate a partnership by the end of 2012, so that it can raise cash from upfront and milestone payments to advance its preclinical assets into clinical development.
"Our preference is to find a partner who is an excellent company, who knows how to do a high-quality job in Phase III and commercialize [ulodesine] in the rheumatology space," he said.
BioCryst is capable of running a Phase III clinical trial if a partner wants the company to stay involved and run the trial, but it doesn't have the resources to conduct a Phase III study on its own, Dr Sheridan said.
Biocryst's ulodesine acts upstream of xanthine oxidase (XO) in the purine metabolism pathway to reduce new formation of uric acid in patients with gout. The oral drug's mechanism of action complements XO inhibitors, such as allopurinol.
"Physicians are looking for new mechanisms of action in their arsenal, because other uric acid-lowering therapies are inefficient," Dr Sheridan said.
Because allopurinol is inexpensive, generic and trusted by doctors, patients and payors, BioCryst's strategy revolves around making ulodesine an add-on therapy to improve allopurinol response rates without a drug-drug interaction.
The company's Phase IIb trial was a 12-week, blinded, randomized study to evaluate the safety and efficacy of ulodesine plus allopurinol in patients with gout who failed to reach the sUA therapeutic goal of <6 mg/dl="" on="" allopurinol="" alone.="" the="" primary="" endpoint="" was="" the="" sua="" response="">
The 52-week extension study provided longer-term safety and sustained efficacy data for 119 patients from the original 279 patients randomized for treatment with 300mg of allopurinol plus placebo or a once-daily 5 mg, 10 mg or 20 mg dose of ulodesine.
The sUA response rates for patients treated with ulodesine were more than twice the response rates for patients on placebo at 12 weeks and the effect was sustained throughout the 52-week extension study. Ulodesine doses of 5 mg, 10 mg and 20 mg/day showed response rates of 45%, 47% and 64% respectively, compared to 19% for placebo.
While there was a low incidence of gout flares, flares were observed in 9-21% of patients treated with ulodesine and just 7% of placebo-treated patients.
In a separate 12-week, Phase II clinical trial, 20 patients with moderate renal impairment were randomized to once-daily treatments with placebo (n=4), or 5 mg (n=8) or 10 mg (n=8) of ulodesine, in combination with 200 mg of allopurinol.
Including that study, a total of 118 patients with mild to moderate renal impairment have been treated with ulodesine across the Phase II program, which confirms that the drug candidate is safe for patients with mild to moderate renal impairment, a common co-morbidity in gout patients, according to BioCryst.
More than 500 patients have been treated with ulodesine in clinical trials.
The drug was generally safe and well-tolerated in BioCryst's year-long Phase IIb extension study in which many patients had multiple co-morbidities, such as hypertension, diabetes and high cholesterol. Clinicians observed no clinical adverse event signals that distinguished ulodesine from placebo, no opportunistic or unusual infections, no signal for other organ toxicities and no fatal or life-threatening adverse events.
"We're very excited about the data we have. We think it's a great opportunity for a mid-cap or large-size pharma company who've got all of the machinery and all of the skill sets to develop and launch and manufacture a drug," Dr Sheridan said.
Discussions with European Medicines Agency (EMA) officials regarding EU requirements for Phase III clinical trials for gout therapies are ongoing, but Dr Sheridan estimated that a Phase III study to satisfy US FDA safety and efficacy requirements will need to enroll 1,700 to 1,800 patients.
Such a trial would cost $100 million, which is not so shocking for a mid- to large-sized pharma company, but it is nearly impossible for a smaller company with $57 million in cash at the end of the first quarter of 2012, which would have to raise capital in the public markets that would be dilutive to existing shareholders, he said.
Instead, the company would rather focus its cash on preclinical assets.
BioCryst wants to file investigational new drug (IND) applications for BCX5191, a nucleoside analog inhibitor of HCV RNA polymerase (NS5B) for hepatitis C, and BCX4161, an oral inhibitor of plasma kallikrein for hereditary angioedema.