BMS, Bavarian Nordic Forge Immunotherapy Collaboration

James Breitmeyer, MD, PhD

A nearly $1 billion windfall licensing agreement involving the immunotherapy PROSTVAC has the company Bavarian Nordic looking toward a long-term manufacturing and distribution arrangement with Bristol-Myers Squibb (BMS).

The deal affords Bavarian Nordic an initial payment of $60 million and the potential for up to $975 million in milestone and upfront payments in exchange for allowing BMS exclusive rights to license and commercialize PROSTVAC, which is in phase III development for the treatment of asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer (mCRPC).

Under terms of the deal, Bavarian Nordic will undertake the manufacturing of PROSTVAC, a pox viral vaccine expressing prostate-specific antigen (PSA). The immunotherapy has shown efficacy as both a monotherapy and in combination with other therapies.

“As monotherapy we have already demonstrated in a randomized phase II study a prolongation of overall survival (OS) of 8.5 months in men with advanced prostate cancer,” James Breitmeyer, MD, PhD, president of the Cancer Immunotherapy Division at Bavarian Nordic’s Mountain View, California campus, said in an interview with OncLive. “That phase II result compares favorably with any other agent that’s available today for prostate cancer.”

PROSTVAC has shown promise as a T-cell priming agent, which enables its combination with other immunotherapies to unleash a more targeted assault on prostate cancer. In combination with BMS’ ipilimumab (Yervoy), as shown in phase I/II studies presented late last month at the 2015 Genitourinary Cancers Symposium in Orlando, Florida, the results are more impressive.

“We think that targeting the immune system specifically and then unleashing it is going to be the wave of the future,” Breitmeyer suggested.

In a phase I NIH study, the combination of PROSTVAC with various doses of ipilimumab resulted in a median OS of 31.3 months for patients with mCRPC. With the 10 mg/kg dose of ipilimumab, the median OS was 37.2 months. Approximately 20% of patients treated with the 10-mg/kg dose were alive at 80 months.

“PROSTVAC is an intelligently designed immune stimulator, developed in conjunction with the National Cancer Institute, that triggers an immune response using PSA that causes a cascading effect so that the immune system is activated to be prepared to kill prostate cancer cells,” Breitmeyer said. “Once our active immunotherapy gets an immune response started, then if you combine it with a checkpoint inhibitor you can get an even stronger response.”

Breitmeyer said PROSTVAC is well tolerated with a typical side effect of “some redness at the injection site, maybe a little bit of fever and achiness. In fact, that’s a sign that the immune system is waking up and doing its job.”

In prior statements, company officials have said the combination with ipilimumab also is well tolerated.

Bavarian Nordic has yet to issue guidance on sales potential for PROSTVAC, said Robert Ang, MD, senior vice president for business development; however the size of the financial deal with BMS suggests that PROSTVAC may have blockbuster potential.

“These trials will support a filing toward the monotherapy indication in prostate cancer, but also BMS is interested in combining this with their immune-oncology portfolio,” Ang said.

PROSTVAC is an “off the shelf” vaccine administered by injection that does not require individual patient blood cell collection, according to Bavarian Nordic statements.

Bavarian Nordic has an ongoing phase III randomized, double-blind, placebo-controlled study to determine whether PROSTVAC alone or in combination with GM-CSF can prolong OS in chemotherapy-naïve asymptomatic or minimally symptomatic men with mCRPC.

“This trial is randomizing patients to receive either vaccine with GM-CSF, which is thought to be immune-stimulating and to enhance the effects of the vaccine; the vaccine plus placebo; or GM-CSF plus an empty vector,” said Harpreet Singh, MD, a clinical research fellow, at the 2015 Genitourinary Cancers Symposium last month.

“That will be the key study for getting PROSTVAC registered as monotherapy for metastatic prostate cancer, and we expect that study to read out sometime in the next two years,” Breitmeyer said.

In addition, Bavarian Nordic is doing studies with the NCI with PROSTVAC and enzalutamide (Xtandi) as androgen therapy, “and those studies are likely to trigger further clinical studies combining PROSTVAC with androgen deprivation therapies, which are of course the standard of care today for metastatic prostate cancer,” Breitmeyer said.

In a statement, BMS said a phase II study is in the planning stages to investigate the combination of ipilimumab and PROSTVAC. The companies have also entered into an agreement by which they may conduct one or more exploratory combination studies of PROSTVAC and agents from BMS’ immuno-oncology portfolio.

“While additional treatment options have become available, mCRPC remains largely incurable,” said Michael Giordano, head of development, Oncology, Bristol-Myers. “Our agreement with Bavarian Nordic reflects our commitment to following the emerging science in immuno-oncology and supports our strategy to transform the treatment of cancer across multiple tumor types, lines of therapy and stages of disease.”