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wo top executives and dozens of other employees of Juno Therapeutics, the company that on Thursday was forced to halt a clinical trial after three leukemia patients died, are alumni of another biotech company that declared bankruptcy two years ago after disappointing sales of its one product.

And the roots of both Seattle companies’ troubles appear similar to some close observers: a failure to adequately heed the scientific challenges of bringing complicated cancer immunotherapies to market. 

“There are echoes here of [the previous company,] Dendreon,” said a health care industry analyst who declined to be named because of concerns it would hurt client relationships. “Both companies were willing to move ahead with something when they had only a superficial, almost cartoonish, understanding of how [the experimental therapy] works at the cellular level. And now three people are dead. … It’s beyond tragic.”

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Dendreon won plaudits for developing a prostate cancer “vaccine” called Provenge in which T cells removed from patients were manipulated so they would attack tumor cells, a forerunner of the CAR-T therapy Juno and other companies are developing for several forms of cancer. But Dendreon, as well as the product, soon ran into trouble.

Shareholders alleged that Dendreon executives, including Chief Operations Officer Hans Bishop, who had nonpublic information about Provenge, sold millions of dollars worth of stock in advance of disappointing news and resulting steep price drops, and that they made false and misleading statements that led investors to think Provenge was more successful than it was. Bishop is now the CEO and president of Juno.

In 2013, Dendreon, Bishop, and two codefendants settled the lawsuit for $40 million without admitting wrongdoing, to eliminate what a company spokesperson at the time called a “potential distraction.”

Dendreon filed for bankruptcy in 2014 and was acquired by Valeant Pharmaceuticals in 2015 for $495 million.

At least 63 Dendreon alumni — including the director of operations, the vice president of regulatory affairs, senior scientists, engineers overseeing quality control, and patient schedulers — joined Juno, according to their LinkedIn profiles. They were led by Bishop and Dr. Mark Frohlich, Dendreon’s chief medical officer and now Juno’s executive vice president of portfolio strategy.

In a Securities and Exchange Commission filing dated June 30 and first reported by the biotechnology news site Endpoints, Bishop said he sold about $4.5 million worth of Juno shares at around $39 a share and exercised stock options for about $280,000 in shares at just over $6.

Juno spokesman Chris Williams told STAT the sales occurred “as part of an asset diversification program,” which is “established only when the seller has no material inside information, and typically involve[s] preplanned sales of a small percentage” of the seller’s holdings.

Juno shares closed down 32 percent on Friday, to $27.81.

But it is the echoes of Dendreon in Juno’s scientific decisions that most worry some experts.

Provenge is a complicated product that involves removing some 25 billion white blood cells from the patient, manipulating them so they target prostate cancer, and infusing them back into the patient. It cost $93,000 for a course of treatment and, in the clinical trial that led the Food and Drug Administration to approve it in 2010, extended the survival of men with advanced prostate cancer by a median of four months.

A 2012 paper in the Journal of the National Cancer Institute questioned the analysis of the key clinical trial that led the FDA to approve Provenge. The authors of that trial, including Frolich and two other Dendreon employees, analyzed some data differently from how they told the FDA they planned to, the JNCI paper concluded.

As a result, the apparent benefit of Provenge was inflated, charged the paper’s authors. In particular, they said, older men in the trial’s placebo group were more likely to die than is typical for men their age with prostate cancer, making Provenge look better by comparison — something that was hidden by the change in data analysis. Dendreon denied any impropriety.

Like Provenge, Juno’s CAR-T therapy is complicated, with numerous moving parts — how many cells to remove from patients, how many to return, what companion drugs should be given.

Part of the way through its clinical trial, Juno said, it decided to give patients fludarabine, a potent drug that destroys T cells, to “make more room” for the genetically-engineered T cells. One investor said it’s risky to change an experimental protocol like that and questioned whether the move, intended to improve the efficacy of the manipulated T cells, was too aggressive.

“They are learning as they go, and I think should have been a little more focused on what can go wrong,” he said.

At Juno’s annual shareholder’s meeting last month, company executives said the worry that kept them up at night was manufacturing, said Brad Loncar, who runs an index of the top 30 publicly-traded cancer immunotherapy companies, not the safety or efficacy of their experimental therapies.

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