DUBLIN – Bavarian Nordic A/S picked up a second bulk supply order for its Imvamune smallpox vaccine from the U.S. government, a $100 million deal that comes on top of the $133 million contract it secured last year. It's further evidence that the transition from liquid-frozen formulation to longer-lasting freeze-dried vaccine is under way.
Imvamune, based on the modified Vaccinia ankara (MVA) vector, is replication-deficient and a safer option for people with inflammatory skin conditions or compromised immune systems than traditional smallpox vaccines based on replication-competent vaccinia virus. The latter is contraindicated in about one-quarter of the population – those with a history of eczema or atopic dermatitis and their household contacts – as the live vaccine can give rise to life-threatening complications.
Production of the new material will be completed in 2017 – Bavarian is currently fulfilling the order from last year. A few steps have to happen before the material arising from each production run can be converted into freeze-dried vaccine doses, however. First, Kvistgaard, Denmark-based Bavarian has to complete the development of a commercial-scale manufacturing process for freeze-dried vaccines.
"It's essentially done," CEO Paul Chaplin told BioWorld Today. The company is finalizing the documentation for submission to the FDA. The U.S. Department of Health and Human Services then has to issue a formal request for proposals (RFP) that would lead to a contract for a specified number of doses.
The company's current expectation is that an RFP will be issued this year, and a contract award will follow in 2017. It's only at that point will the price per dose become fixed – and the full value of the supply contract will become apparent. "This is just bulk and will be a portion of the final dose price," Chaplin said. Under its last contract – for 8 million doses of liquid-frozen Imvamune – it secured $29 per dose. "We believe we'll be able to negotiate an increase in the freeze-dried dose price, but time will tell," he said.
The last contract completed the delivery of 28 million doses to a national strategic stockpile containing 20 million doses (the surplus allows for the phased expiry of lots manufactured at different times). It was inked back in 2013. Since then, cost of goods increases and inflation would push the per-dose price up to $34 or $35, Chaplin said. But the company hopes to gain a premium for the new formulation. "It's a superior product. It will have a longer shelf-life," he said. That will drastically cut the need for replenishment – the liquid-frozen version had a shelf-life of three years. "We don't have a final shelf-life [for the freeze-dried product]. We anticipate it will be at least 10 years," he said.
The company maintains a dual focus on developing therapeutic cancer vaccines as well as prophylactic vaccines for infectious disease. A phase III trial of its prostate cancer vaccine, Prostvac (rilimogene galvacirepvec/rilimogene glafolivec), is ongoing, with a full data readout expected in the next 12 to 18 months. Two interim readouts are due before then. In the coming weeks, it will also kick off two phase II combination trials in prostate cancer with its partner, New York-based Bristol-Myers Squibb Co. In one three-arm study, patients will receive either Prostvac, BMS's CTLA-4 inhibitor Yervoy (ipilimumab) or a combination of the two. "It's a real mechanism-of-action study," Chaplin said. In the second, patients will receive either Prostvac plus Yervoy or Prostvac plus Yervoy plus Opdivo (nivolumab), BMS's PD-1 inhibitor.
The company is also gearing up for a phase II trial of its vaccine against respiratory syncytial virus (RSV), MVA-BN RSV, which is undergoing a phase I study. The phase II study, which will get under way in advance of the RSV season, will recruit 400 elderly volunteers. All going well, a phase IIb trial will follow next year.
It also plans to further explore the combinatorial potential of its therapeutic cancer vaccine CV-301 (formerly Panvac), which is undergoing a phase II trial in bladder cancer. "We want to show proof of concept in three different cancer indications," Chaplin said. It plans to pair the vaccine with Opdivo in a phase II trial in lung cancer later this year. Next year, it is considering combination trials in bladder cancer and colorectal cancer.
The approval in bladder cancer this week of Genentech Inc.'s PD-L1 inhibitor, Tecentriq (atezolizumab), gives Bavarian an option to do a combination trial in that indication without having to enter a formal clinical collaboration, of which there are now several dozen in immuno-oncology. "There are a lot of clinical collaborations, but our experience of talking to companies is there are a lot of strings attached," Chaplin said. Discussions with various potential partners are ongoing as well.
The firm has plenty of cash to conduct exploratory trials, having raised DKK665 million (US$100 million) in a private placing in April. It reported DKK972 million in cash at the end of the first quarter.