Xbiotech Responds to ESMO, Other Critics of Phase 3 Cancer Data

Xconomy Texas — 

Austin—It’s been a wild couple of weeks for Austin, TX, drug developer Xbiotech.

On July 2, the maker of a monoclonal antibody that aims to treat colorectal cancer released additional details from a Phase 3 study. Its CEO calls the results beyond doubt “a breakthrough.” But investors, peers, and the medical society whose conference was the backdrop to the announcement aren’t responding that way.

The European Society of Medical Oncology (ESMO) hosted the meeting in Spain where Xbiotech (NASDAQ: XBIT) touted its data, and an executive board member of the group said in a statement released Thursday that the results are not reliable and criticized the way the company reported its data.

“The jury is still out on whether the study made sense but as the results do not bear close inspection, they also cannot be relied upon,” said Dirk Arnold, the board member and a professor at Instituto CUF de Oncologia in Lisbon. “It’s not yet clear whether there is any benefit in translating this trial into practice.”

The trial in question aimed to measure whether a higher percentage of 207 late-stage cancer patients who received the drug Xilonix showed a “response,” compared with 102 who took a placebo. The response the company was looking for is an increase in lean body mass, as well as improvements (based on a survey) in the patients’ fatigue levels, pain, or appetite. Xbiotech said that 33 percent of people who took Xilonix responded, while 19 percent who took a placebo responded.

The company also combined the responders from among both placebo and drug takers when it presented overall survival data. Because of that combination, which was the new information, it’s not possible to discern the direct connection the treatment may have had on overall survival, say critics.

The company reported that people who responded to both Xilonix and placebo lived 11.5 months after the trial, compared with the “non-responders” to the drug and placebo, who lived 4.2 months.

A former editor of the Journal of Clinical Oncology had even harsher words for the company.

“Just saying responders do better than non-responders is bogus,” University of California, San Francisco professor of medical oncology Alan Venook told Xconomy. “If you wanted to get an immediate rejection [from the journal], that was for sure the easiest thing to do.”

The data may be meaningful, Venook says, but it’s hard to tell from Xbiotech’s limited report. Without more information, Xbiotech’s statement is akin to saying “people who respond do better than people who don’t respond because they do better. It’s self-evident,” Venook says.

Xbiotech stock was down 15.5 percent to $15.39 at the close of trading Thursday.

The Xbiotech report sparked strong reaction when it was first released. On July 5, TheStreet.com’s biotech reporter Adam Feuerstein called the results “confused” and “absurd.”

“XBiotech is confident in the Xilonix Phase III data presented at ESMO,” a company spokeswoman said today. “We fundamentally disagree with Dr. Arnold’s interpretation of the data and look forward to further discussion in an appropriate scientific forum.”

In an interview with Xconomy last week before the ESMO statement was released, Xbiotech CEO John Simard said that the company accomplished what it set out to do: Xbiotech was looking to see if there would be a response in people who took Xilonix, and when it saw one from the drug compared with placebo, it could say the response was related to the treatment, Simard said.

“You will respond in this primary way, and when you’re a responder, you’re going to live three times longer than the rest of the folks that aren’t achieving that response,” Simard said. “We have an endpoint where you can tell whether patients will live three times longer or not.”

When asked to comment about Venook’s criticism, Simard reacted with sarcasm: “OK, thanks guy, then I’m glad you’re on board.”

Xbiotech has not yet published the full data from the trial. The data under fire were an overview, but Simard said that critics like Venook shouldn’t need additional data to understand Xbiotech’s positive view of the study.

“We had to formally show they’re living longer, but what we show is that the response is related to the drug,” Simard said. “That’s a pretty simple concept. How can you malign that?”

Simard attributed criticism of the data to stock manipulators. In the first two trading days after the company’s July 2 statement, the stock price fell 42 percent.

Simard also addressed criticism that moving patients from placebo to the drug—a practice called “crossover”—made it difficult to interpret side effects and other elements of the trial. Simard said providing patients a placebo is a “cruel thing to do” and crossovers should in fact happen more frequently in trials. Xbiotech moved placebo patients to the drug arm after eight weeks. Simard remained steadfast that the overall survival data holds value.

“They’re living three times as long,” he said. “Clearly we got the disease under control somehow.”

When asked when the full Phase 3 data will be published, Simard said that it is currently under review at a “top” scientific journal. In addition to colorectal cancer, Xbiotech is studying its treatment for multiple other conditions, including other cancers.

Xbiotech currently leases two buildings near the Austin-Bergstrom International Airport to produce its drugs. It is building a new facility, which it expects to move in to later this year. The company raised $76 million in an initial public offering in April 2015.