Dendreon CEO Jason O’Neill

From its founding in 1992, Dendreon’s fortunes have risen and fallen with the sales of its flagship product, its sole marketed drug Provenge® (sipuleucel-T), an autologous cellular immunotherapy for prostate cancer that won the FDA’s first approval for a cancer immunotherapy in 2010.

Identifying a second revenue stream and improving commercial operations were two key priorities for Dendreon CEO Jason O’Neill when he took the helm in June 2020. With production capacity exceeding demand for Provenge, Dendreon says it has identified that potential second growth pillar—contracting out its substantial manufacturing, process development and logistics expertise to offer end-to-end manufacturing of cell therapies as well as services such as patient logistics for other companies.

“It’s not always obvious to create a very different kind of business and build it into your existing business,” O’Neill told GEN Edge. “But as I came on board and took stock of what we have in our hands and looked more at the market dynamics, we said, ‘Wow, we’ve got an enormous number of compounds—really promising ones—that are approaching FDA approval and there’s a very small number of companies that have any experience managing late-stage manufacturing.”

Dendreon has tracked about 220 cancer immunotherapy compounds as being in Phase II or Phase III development, with about 60% of cell therapy developers outsourcing their manufacturing. But many of those companies lack the internal expertise of Dendreon: Half of its workforce has been with the company since 2015, and 40% since 2011. Dendreon says it is one of only four companies manufacturing cell therapies for commercial use in the U.S.

“It’s a huge investment for these companies to just build their own infrastructure. You’re talking about a couple hundred million dollars before you’ve actually got an FDA approval.  That’s just a gigantic risk,” O’Neill said. “So we realized, there was a huge demand for infrastructure, we’ve got really unique level of expertise and we just realized, it was a perfect combination of things coming together where we really have a role to play here.”

O’Neill would not disclose how much Dendreon has invested in its new division, though he did say about 150 of the company’s approximately 500 employees will carry out its work of contract manufacturing and services.

Logistics and Commercialization

Among those services will be patient logistics—ensuring that companies track the chain of identity (COI) on every patient to make sure their cells are delivered to them and not another patient. The company’s transportation and patient operations team reports a 99% success rate receiving and delivering shipments within an 18-hour window.

“We’ve built up systems over time that are really integrated software systems to track patients, track flights, make sure the hand-off is seamless and increasingly the agency’s requiring companies to have a plan for maintaining COI,” O’Neill said. “Not only do we have the manufacturing capability, but we’ve also got the logistical capability and a network of apheresis centers [about 150] that are helpful in launching larger scale and clinical studies.”

That focus on larger-scale trials has compelled many cancer drug developers to concentrate on drawing patients to a handful of larger tertiary care centers, forcing them in many instances to travel long distances to participate in clinical trials.

“Because of the infrastructure we have, we enable companies to move faster and implement trials more rapidly, and I think in a space like prostate cancer, where we operate currently, it’s really competitive. There are more studies out there trying to recruit patients, so I think having that network really is an accelerator for a lot of our partners.”

Another service Dendreon plans to offer is commercialization assistance to oncology drug developers.

“We do find some partners out there that are in the prostate cancer space, that are not only interested in a partner who can help them bring their product forward to approval, but also in some cases, maybe interested in partnering up and finding a commercial partner to launch those products,” O’Neill said. “So in a way, it’s a good opportunity for us to use our expertise today to really enable the future of immunotherapy, but also to participate, when we find the right combination of partner and therapeutic area, where we think we can bring some unique expertise.”

Interest and infrastructure

Dendreon says its contract manufacturing and service overtures have seen immediate, positive feedback from potential customers, which the company envisions as biopharmas developing CAR-Ts, autologous, or allogeneic cell therapies: “I think we’re very close to landing our first partner and announcing that,” O’Neill predicted.

Dendreon’s contract manufacturing and services infrastructure starts with an over 180,000-square-foot, cGMP-compliant and FDA-approved manufacturing site—one of Dendreon’s two immunotherapy manufacturing facilities—in the company’s headquarters city of Seal Beach, CA. [Dendreon]
While investment in the division began last year, O’Neill said, Dendreon had the advantage of already having substantial infrastructure in place, starting with an over 180,000-square-foot, cGMP-compliant and FDA-approved manufacturing site—one of Dendreon’s two immunotherapy manufacturing facilities—in the company’s headquarters city of Seal Beach, CA, about 30 miles south of Los Angeles.

That facility, according to Dendreon, contains more than 50,000 square feet of modular clean rooms, and enjoys a manufacturing success rate of 99.6%. In May 2019, Dendreon inked a long-term lease agreement extending its presence at the facility through 2030.

Also within Dendreon’s manufacturing infrastructure:

  • A second immunotherapy manufacturing facility, a 155,000-square-foot site in Union City, GA, located just outside the Atlanta Metro area near Hartsfield-Jackson Atlanta International Airport. Dendron also inked a 10-year lease for that site in 2019
  • A nearly 80,000-square-foot office and laboratory site in Seattle’s South Lake Union section, which will serve as the company’s process development and manufacturing sciences center. Seattle is home to Dendreon’s operations and medical organization.

“It really will play a very big role for us, and I think, very quickly,” O’Neill said of the new division. “We’ve had some success with Provenge. We occupy a really clear niche in the marketplace and I think we can expand that. But I think over time, the contract manufacturing and services division could match or potentially eclipse the total sales of the Provenge business that we have today.”

Sub-$500M Brand

Privately-held Dendreon does not disclose sales of Provenge beyond O’Neill saying that they are now “a sub-$500 [million] brand.” By contrast, the world’s top-selling cancer immunotherapy, Merck & Co.’s blockbuster Keytruda® (pembrolizumab), generated $14.38 billion in 2020 worldwide sales, up about 30% from 2019—with first-quarter sales rising 19% from Q1 2020, to $3.899 billion.

The world’s top selling prostate cancer drug, Pfizer/Astellas Pharma’s Xtandi® (enzalutamide), racked up $5.048 billion in 2020 revenues, combining ¥444.8 billion ($4.024 billion) in sales recorded by Astellas with the $1.024 billion Pfizer collected in revenues from its alliance with the Japanese pharma. Xtandi revenues jumped nearly 19% from the $4.254 billion collected by both companies in 2019.

During the first quarter, Xtandi generated a total $1.314 billion in revenues—consisting of ¥115.7 billion ($1.047 billion) in Astellas sales, and $267 million in alliance revenues recorded by Pfizer.

Provenge sales were set back last year by the COVID-19 pandemic, O’Neill acknowledged, as healthcare providers held off on cancer procedures and diverted efforts to treating patients with SARS-CoV-2.

That decline “may have accelerated a little bit” Dendreon’s move into contract manufacturing and services, O’Neill said—an option the company’s board had considered for years.

“When we really looked into it, it seemed that the market was telling us it was time now to get involved. The idea had been there, prior to my arrival and I think, as we looked at the future there’s just a lot of urgency for us to make progress on two of our key objectives we had,

Provenge is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

Speaking with GEN Edge last year, Dendreon founder and former CEO Mitchell Gold—who oversaw Provenge’s advance from clinic to patients more than a decade ago—said the company’s prostate cancer drug faced two initial challenges upon approval.

One was its list price, which at an initial $31,000 per infusion was considered eye-poppingly high; that list price has since risen to $45,000 per infusion. The other challenge was lingering skepticism about the effectiveness of weaponizing the immune system against cancer.

“I know this is hard to believe now, but you have to go back—no one believed the immune system could actually be used to fight cancer. That concept of immuno-oncology was just not believed in. And I think because we were first, we had all the headwinds. We had to prove that,” recalled Gold, who went on to become co-founder and managing partner of life sciences investment firm Alpine BioVentures, and Executive Chairman and CEO of drug developer Alpine Immune Sciences.

Paradigm Shifts

O’Neill said Provenge was also challenged by several paradigm shifts in medicine that included the rise of dose-dense therapies with less time between treatments.

Provenge is administered intravenously in a schedule consisting of three intravenous dose infusions at approximately two-week intervals. Each dose is preceded by leukapheresis approximately three days before the scheduled treatment, and is administered only to the patient from whom the cells were obtained. Dendreon has established agreements with about 150 apheresis partners across the United States.

A treatment course of Provenge typically takes one month, compared with oral prostate cancer therapies like Xtandi and Janssen Biotech (Johnson & Johnson)’s Zytiga®, where clinical trials showed median treatment durations of 13.8 months and 11 months, respectively.

However, Xtandi and Zytiga has significantly lower list prices according to Drugs.com— $12,825 for 120 40-mg capsules of Xtandi; $11,376 for a supply of 120 250-mg tablets of Zytiga. (Xtandi is dosed at 160 mg daily; Zytiga, at 1000 mg daily taken in combination with prednisone.)

“Insurers like to pay for things as patients receive them, so that if a patient changes insurance providers in a given year, then they’re not paying the entire therapy for that patient for a lifetime,” O’Neill said. “Products in this category are high value products and they’re priced in that range. When we take a look at actual cost comparisons, Provenge is actually less costly than many of those therapies because it’s not the kind of a drug that gets prescribed over a long time period. That was one of the challenges we faced.”

Xtandi and Zytiga may figure in Provenge’s future in another way—as potential future combination indications. Dendreon opened the door to those last October, when it published an analysis of Medicare claims data from more than 6,000 fee-for-service beneficiaries. The analysis, published in Advances in Therapy, showed that adding Provenge to either Zytiga or Xtandi at any point in a patient’s metastatic castration-resistant prostate cancer treatment regimen reduced the risk of death by 41% and prolonged median overall survival by 14.5 months.

“The category of prostate cancer hasn’t really gravitated towards combination treatments as much as lung cancer and other areas where it’s much more common. We’re seeing some really terrific results when this drug is layered on top of leading orals like Zytiga and Xtandi,” O’Neill said.

Ongoing Phase III Trial

Dendreon is also assessing Provenge monotherapy in the ongoing Phase III ProVent trial (NCT03686683), a randomized open-label study designed to assess the efficacy of Provenge in reducing the progression of newly-diagnosed non-metastatic prostate cancer compared to patients followed on active surveillance as standard of care. ProVent continues to enroll patients with an estimated enrollment of 450, and data expected in late 2022.

“If that study meets its primary endpoint, I think it will be a really exciting day for patients in general, because we just don’t have any great options early in treatment. And it’s where immunotherapies are really at their best,” O’Neill remarked.

Whether it was Provenge’s list price or other factors, Dendreon struggled in its early years with underperforming sales and increased competition from other developers of cancer treatments, filing for Chapter 11 bankruptcy protection in 2014. Dendreon’s assets were sold the following year to Valeant Pharmaceuticals (now Bausch Health), which in 2017 sold Dendreon to Chinese-owned Sanpower Group for $820 million. Sanpower sold Dendreon a year later to Chinese department store chain Nanjing Cenbest for CNY 5.97 billion ($924 million).

Dendreon’s numerous changes in ownership led to a parade of CEOs and others running the company. Gold was replaced as Dendreon’s CEO in 2012 by John H. Johnson, who stepped down two years later for another Johnson & Johnson veteran executive, W. Thomas Amick. That year, Amick oversaw the layoff of 600 staffers, nearly half the company’s workforce at the time.

Amick himself was among 77 Dendreon staffers laid off in 2015 after Valeant bought the company, leaving oversight to a CFO/Treasurer and a President/General Counsel. Valeant’s president, James Caggiano, took Dendreon’s helm in 2017, to be succeeded by O’Neill last year. O’Neill’s previous experience included a stint as CEO of Iridium Therapeutics and leadership of Sanofi’s oncology portfolio during six of his nine years with the big pharma company. That portfolio included Taxotere® (docetaxel), the leading chemotherapy in the metastatic prostate cancer setting.

“I’m definitely drawn to opportunities to build new things and turn things around,” O’Neill said. Dendreon has had “a fairly up and down history—Immense progress when Provenge first came out, and it found a nice little niche that’s growing. But it has not been what we see with immunotherapies in other categories today for a variety of reasons.”

O’Neill saw “an opportunity to repolish an old gem. We’re on our way to doing that. I think now there’s an opportunity for the company to really find a second path and really make a big contribution, so we’re really excited about it.”