Therapeutic cancer vaccines harness the patient's own immune system to fight tumours. Credit: Rolf Ritter/Cultura Science/Getty

The first therapeutic cancer vaccine to be approved in the United States will stay on the market despite the financial collapse of the trailblazing biotechnology company that developed it. The vaccine, Provenge (sipuleucel-T), was purchased on 23 February by Valeant Pharmaceuticals of Laval, Canada, which paid US$415 million for the prostate-cancer treatment and other assets of the bankrupt Dendreon Corporation.

The now-defunct Dendreon, of Seattle, Washington, made history in 2010 by showing that complex treatments made fresh for each patient could win regulatory approval, and could be expanded beyond the realm of specialized academic hospitals. Industry took note: today, experimental cancer therapies that spur patients' immune cells to attack tumours are among the hottest properties in biotechnology.

“Dendreon had vision and foresight,” says Usman Azam, head of cell and gene therapies at Novartis, a Swiss pharmaceutical company that has purchased one of Dendreon’s manufacturing plants to fuel its own cell-therapy efforts. “Don’t view Dendreon as a failure: it paved the way.”

But although Dendreon created the market for cell therapies, it ultimately could not survive in it.

Primed for attack

Provenge is made by harvesting a patient’s dendritic cells — a type of immune cell — and then mixing them with a protein that is particularly abundant in prostate tumours. This primes them to recognize and attack the tumour; the cells are then infused back into the patient.

The technique was pioneered in the early 1990s by Edgar Engleman, an immunologist at Stanford University in California, who had seen promising results in animal studies of a different cancer, lymphoma. Engleman teamed up with fellow Stanford immunologist Samuel Strober to work out ways to make the process more efficient.

When the two pitched their idea for a company to investors, they had little clinical data and were too optimistic about how fast the treatment could reach patients, says Strober. The company was an enormous gamble: harnessing the immune system to fight cancer was still a controversial idea, and no other company had marketed a therapy so personalized and labour-intensive. “But at that time it was a little different from now,” says Strober. “Companies were getting funded on the basis of promise, rather than actually looking at their capacity for early commercial success.”

Engleman and Strober founded Dendreon in 1992; the US Food and Drug Administration approved Provenge in 2010.

Short-lived victory

The approval was celebrated as an important proof of concept by researchers working to develop cancer vaccines and other treatments that stimulate immune responses to the disease. But Dendreon, already strained by the long wait for approval, soon ran into financial difficulty.

The United States’ publicly funded Medicare system decided in 2011 to pay for Provenge treatment. But confusion over how the cost of the vaccine would be reimbursed by private insurance companies left many US doctors hesitant to use it, says Corey Davis, an analyst at Canaccord Genuity, an investment bank based in Toronto, Canada. When revenues came in far below the company’s initial estimates, Dendreon failed to adjust its operations accordingly, Valeant chief Michael Pearson told investors on 23 February.

Provenge is, at first glance, an odd purchase for Valeant, a company known for acquiring relatively simple, established products — for example, it controls 10% of the US contact-lens market. But Valeant saw an opportunity to cut costs and improve how the vaccine is marketed to doctors, and thinks it can make back its investment in less than two years, says Davis.

The vaccine’s rescue is a relief to Engleman, who had feared that Provenge might disappear along with Dendreon. As the company struggled financially, the scientists who founded it watched helplessly from the sidelines. “This was our baby,” says Engleman. “It was extraordinarily frustrating. There was nothing we could do.”

Early choices

In retrospect, Engleman says, some early scientific choices may have exacerbated Dendreon’s struggle. The company decided not to develop ways to freeze the stimulated immune cells, he notes, which could have simplified the procedure and lowered its cost.

Both scientists lament the choice of prostate cancer as the inaugural disease target of the technology. Although the early lymphoma data had been very promising, recalls Engleman, the company decided to switch to a more common cancer with a bigger potential market. And prostate cancer had another advantage: people can live without a prostate, which helped to calm fears (since proved unfounded) about what would happen if the primed immune cells attacked healthy tissue.

But the results in prostate cancer were not as dazzling as Engleman had hoped on the basis of his animal results in lymphoma. Dendreon did extend survival in some people with advanced prostate cancer, but by a median of only four months1. This week, the UK National Institute for Health and Care Excellence advised that at more than £47,000 (US$73,000) per course of treatment, Provenge is too expensive to justify its use by the National Health Service.

The Dendreon experience has not dampened Engleman’s enthusiasm for entrepreneurship. He and Strober, along with other collaborators, have teamed up on a company that aims to develop a technique to reduce the likelihood that recipients of transplanted organs will develop an immune response to the new tissue.

They are again on the hunt for funding, but this time the team is backed by more than a decade of clinical-trial data that supports the method. “We’re thinking that this one will progress a lot faster than the Dendreon thing,” says Strober.