Washington Editor

BioCryst Pharmaceuticals Inc. appears to backing off its development plans for intravenous Fodosine (forodesine) in T-cell acute lymphoblastic leukemia/lymphoma (T-cell ALL) for a couple of reasons, though that's not definitively decided, as a potentially quicker path to approval gets ramped up.

Among apparent deficiencies associated with the intravenous formulation, which has been tested exclusively in T-cell ALL, its beneficial effects don't appear as strong as previously believed in that setting, according to updated Phase IIa data. In addition, a stability problem has prompted the Birmingham, Ala.-based company to suspend a Phase IIb study in the same indication.

Those disclosures on Tuesday led to a decline in its stock value, with the shares (NASDAQ:BCRX) down 16.5 percent, or $1.58, to $8.

"We need to continue the investigation and wrap that up," CEO Jon Stonehouse told BioWorld Today, "and in parallel we need to discuss the future of T-cell ALL with our partner."

The drug, which blocks an enzyme called purine nucleoside phosphorylase, or PNP, is the subject of an oncology agreement with Mundipharma International Holdings Ltd. That firm, of Cambridge, UK, is responsible for Fodosine's overseas development and reimburses an undisclosed portion of BioCryst's domestic development efforts. And Stonehouse doesn't expect this bump in the road to impact their relationship, noting that "at this point" nothing indicates that Mundipharma is "not fully engaged in Fodosine and supportive of moving forward" with it.

So going forward, BioCryst believes an oral formulation for cutaneous T-cell lymphoma (CTCL) could get Fodosine to market faster.

The capsules being used in other Fodosine studies, including a pending CTCL trial, are not affected and will continue as planned. In the past year the company has generated clinical data that point to the drug's activity and safety in this setting, so given the delays associated with the formulation issues impacting the T-cell ALL trial, as well as the limited number of patients with T-cell ALL who are eligible to be treated under that protocol, BioCryst will focus its resources on CTCL.

As a result, the company has requested a special protocol assessment with the FDA to secure an appropriate clinical trial design. While a decision on that proposal is up to the FDA at this point, James Alexander, BioCryst's chief medical officer, said the company has planned to start the Phase IIb study later this year.

"We've got a very dedicated group of investigators that have been working with us for years on the previous trial, and they still have patients being treated," he told BioWorld Today. "They're ready to move to the next trial, and we are too."

It's expected to provide efficacy and safety data to support a regulatory submission, Alexander added, though he declined to provide any design particulars until the FDA agrees to them.

The drug also has been tested to a smaller degree in chronic lymphoid leukemia and B-cell ALL.

The flaws with intravenous Fodosine include more complete data from a Phase IIa trial in T-cell ALL that indicate that the response rate appears to have decreased from the 18 percent reported in December at the American Society of Hematology meeting. Since that initial report, patients continued to enroll and the study has progressed toward the target number of 80 subjects treated.

"Frankly, many of the case books are still out in the field, and we're looking at them as they come in," Alexander said. "We've noticed that the response rate was not as high as we had last reported."

But he added that "we don't really have anything" to pinpoint a cause for the decreased efficacy. "We know that therapies have changed, patients have been more heavily treated and more refractory to treatment," Alexander said. "So until we look at the data in detail, we really can't speculate."

In addition, recent stability results detected particulate matter in clinical batches of intravenous Fodosine that seems to stem from the vial stoppers used in clinical packaging, which may result from an interaction between a component of the stopper and a component of the drug solution. Assay data do not suggest any decrease in the potency of Fodosine's active product, but the partners will work together to identify the best path forward for this formulation.

Further drug development milestones on the short-term horizon for BioCryst, which ended the year with $46.2 million in cash reserves, include plans to start Phase II studies of another PNP inhibitor called BCX-4208 for an autoimmune indication, furthering a Phase II trial of an intramuscular injection of peramavir for seasonal flu and advancing a series of preclinical candidates. BCX-4208 is partnered with F. Hoffmann-La Roche Ltd., of Basel, Switzerland.

"We're much more than a one-product company," Stonehouse said. "There's a lot of value in BioCryst."