Sunesis Waits Out Suspenseful Final Year of Pivotal Leukemia Trial

7/2/13Follow @tanseyverse

The next 12 months will be a transformational period for South San Francisco-based Sunesis Pharmaceuticals (NASDAQ: SNSS), no matter what the outcome of the ongoing late stage trial of its lead drug candidate, vosaroxin.

Sunesis, which now has 30 employees, could be reborn as an expanding commercial oncology company if vosaroxin proves to lengthen the lives of patients with acute myeloid leukemia (AML), a fast-moving blood cancer that has thwarted other attempts at significant treatment improvements for decades. If vosaroxin becomes Sunesis’ first product, it would also be the first cancer drug that belongs to a family of chemicals now used primarily to make antibiotics. Sunesis hopes to establish a wider franchise for vosaroxin in other blood cancers and possibly in solid tumors, becoming “the next great hematology business,” says CEO Daniel Swisher.

“We’re kind of on this tipping point,” says Swisher. “We have the opportunity to be a 200-person organization.” But a disappointing release of the trial data expected next year would immediately roll back the timeline for Swisher’s vision of Sunesis as a growing commercial company that would follow in the footsteps of its neighbor Onyx Pharmaceuticals (NASDAQ: ONXX) of South San Francisco, and Summit, NJ-based Celgene (NASDAQ: CELG), which have each pioneered drugs for another blood cancer, multiple myeloma.

While the vosaroxin trial could make Sunesis’ fortune, there’s a chance it could tip the other way, as far as the company can predict from the limited hints that have emerged from a series of reviews by an independent data and safety monitoring board. Such outside boards keep the results from blinded trials under wraps, but they can stop a trial if no benefit can be expected or if side effects are unacceptable. The board has given the thumbs-up for the vosaroxin trial five times since the study began three years ago. The most recent go-ahead came this month. But in September, the board also concluded that Sunesis should expand the trial’s size from 450 to 675 participants to make it more likely to yield statistically significant results.

Sunesis CEO Daniel Swisher

Sunesis CEO Daniel Swisher

This suggests that vosaroxin may not deliver the largest survival increase hoped for by the company. That would have increased the median overall survival from five months to seven months—an improvement of 40 percent. But the trial still holds out the possibility of showing a significant survival benefit in patients who have run out of treatment options, Swisher says.

AML strikes most often in people over 60, and patients can die within a year after diagnosis. The standard first treatment for newly diagnosed AML patients is the drug cytarabine plus a form of anthracycline. Some people don’t respond at all, while those whose disease goes into remission usually relapse within a year.

This is the patient population in Sunesis’ late-stage VALOR trial. If vosaroxin increased the median survival time the range of individual responses might be broad, with some patients possibly gaining more than a year. In the trial, vosaroxin is paired with cytarabine in the treatment arm, while other trial participants receive cytarabine and a placebo.

Vosaroxin is a chemical cousin of quinolone antibiotics such as ciprofloxacin, which fight the spread of bacterial infections by preventing replication of the DNA in microbes. Vosaroxin works via a similar mechanism in fast-growing cancer cells, such as the immature blast cells in the bone marrow that proliferate uncontrollably in AML. The experimental drug prevents DNA repair enzymes from fixing breaks in the DNA, triggering the death of cancerous cells.

The goal is a complete remission, or the absence of detectable leukemia cells in the blood and bone marrow. A remission can clear the way for a bone marrow transplant among patients who might benefit from that further treatment.

For Sunesis, the ultimate aim would be to advance vosaroxin as a frontline treatment for AML, replacing anthracyclines as an element of the two-drug chemotherapy regimen. Aside from any survival advantage, vosaroxin doesn’t appear to cause the heart toxicity associated with anthracyclines, Swisher says. And as far as researchers know, two common mechanisms that cancer cells use to become resistant to the effects of drugs won’t work against vosaroxin.

That said, a similar drug called amonafide that also showed promise in early clinical trials failed in a Phase III trial in 2011, sinking the prospects of UK-based drug developer Antisoma. Wall Street oddsmakers have been making bets that the Sunesis trial will also fail. They read the September decision to expand the trial population as a negative signal, according to TheStreet.com.

Swisher says the critics missed the hopeful signs in that pre-planned, interim review of the data so far.

“That bearish argument is not very informed in terms of really understanding the trial design,” Swisher says.

VALOR has an adaptive trial design that contemplated a one-time increase in enrollment to maintain the statistical power of the study, he says. The data and safety monitoring board’s evaluation, which placed the results in a pre-specified category defined as “promising,” triggered a $25 million payment to Sunesis by the life sciences investment firm Royalty Pharma, which gained royalty rights of 6.75 percent on future vosaroxin sales.

Sunesis has other avenues to pursue if its leading drug candidate falls short of the results needed for regulatory approval. The company could explore the use of vosaroxin in solid tumors such as ovarian cancer, as a frontline treatment for elderly AML patients who can’t withstand standard therapies, and as a therapy for myelodysplastic syndrome, a precursor of AML. Sunesis also has early stage clinical collaborations with Millennium/Takeda and Biogen Idec, which each include the possibility of milestone payments up to $60 million as well as product royalties. The company says its $61 million in cash will carry it past the announcement of the VALOR trial results in 2014, when it hopes to file for US and European regulatory approval for vosaroxin. If approved, the drug could be on the market in 2015.

Sunesis, which retains ownership of vosaroxin, estimates peak revenues at $700 million to $1.26 billion by 2020, assuming that the drug is used to treat about a quarter of the 49,000 relapsed and refractory AML patients in the United States and Europe. The US price for a treatment cycle would be $80,000 to $100,000.

“AML alone is a billion dollar revenue opportunity for Sunesis,” Swisher says.

Bernadette Tansey is a freelance journalist based in Berkeley, CA. Follow @tanseyverse

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