The high-risk world of cancer-fighting vaccines and oncolytic viruses received a new endorsement with Amgen’s chunky purchase of privately held developer BioVex. For $425m upfront, the California biotech snaps up a late-stage candidate that aims to selectively infect malignant cells and simultaneously invoke a tumour-destroying immune response, a therapeutic approach that so far has struggled to deliver clinical success.
With phase III data on the horizon, Amgen’s acquisition provides an unexpectedly-timed exit for BioVex’s venture capital backers. After almost unheard of series F and G funding rounds to finance two pivotal trials of OncoVex, investors in the UK group received an offer too good to refuse – counting milestones, the total deal value comes to $1bn.
OncoVex the lever
OncoVex is the jewel in BioVex’s crown. It is being tested in combination with cisplatin in squamous cell head and neck cancers and as a monotherapy for malignant melanomas. Both pivotal trials are being conducted under special protocol assessments agreed with the FDA, reducing the chances that trials, if successful, would be challenged because of clinically questionable endpoints.
To fund the trials, BioVex raised $80m in 2009 in two rounds which, combined with a more recent financing, provided a cash runway through 2012, says Sander Slootweg, a BioVex board member and managing director of Netherlands-based venture backer Forbion.
Amgen’s entry on the scene was unexpected, giving investors an early exit option; BioVex's strategy had been to wait for phase III results and then seek an exit for investors, with options ranging from licensing to a trade sale to an initial public offering.
“I think we were not looking to sell at this moment,” Mr Slootweg says. “It came a bit early, but when a party like Amgen approaches you, you have to consider (its offer) very carefully."
BioVex’s approach is not dissimilar to that of therapeutic vaccines being trialled in cancer. OncoVex is a genetically altered strain of herpes simplex virus engineered to enter only tumour cells. It is injected directly into the tumour, causing cell death and priming a patient's immune system to attack other cancerous cells.
The phase II results were clearly promising enough to green-light the pivotal trials. In metastatic melanoma, investigators found no evidence of disease in 13 of 50 patients after 18 months, and in head and neck cancer, the virus achieved a 76.4% overall response rate.
The phase III trials are measuring the OncoVex/cisplatin combination against radiotherapy, in the case of head and neck cancer, and against an immunostimulant in the case of melanoma.
Speaking to EP Vantage prior to the Amgen deal, BioVex’s founder and chief technology officer, Robert Coffin, likened the developmental history of oncolytic viruses to that of monoclonal antibodies and cancer vaccines.
The phenomenal success of antibodies today belies a long and chequered developmental history. According to Mr Coffin: “Antibodies went through a major crisis, from which it nearly didn’t recover and if it wasn’t for Rituxan it probably wouldn’t have done”.
The approval of Rituxan in 1997 for non-Hodgkin's lymphoma really did open the floodgates for antibody technology and Mr Coffin is naturally hopeful that regulatory approval for OncoVex could have a similarly positive effect in the oncolytic virus space.
Dendreon the trailblazer
More recently, FDA approval of Dendreon’s cancer vaccine breakthrough Provenge followed a similarly tough journey for the product itself and cancer vaccines in general. As such, the ‘Provenge effect’ continues to boost the sector and may have encouraged Amgen – it is interesting to note that BioVex has recently been positioning OncoVex more as a cancer vaccine than an oncolytic virus.
Assuming efficacy can be established, coupled with a relatively benign safety profile by most cancer drug standards, oncolytic viruses certainly have potential commercial and therapeutic value on a par with antibodies.
Mr Coffin believes oncolytic viruses have potential to be used across the spectrum of cancer treatment, from early to late stages of disease, as a monotherapy or in combination with chemotherapy, or in an adjuvant setting.
“Oncolytic viruses can be layered on to anything due to their mild safety, just flu-like symptoms, whereas other cancer combinations tend to add toxicity”, says Mr Coffin.
Still, despite the promise, and Amgen’s gamble, they remain unproven; OncoVex could be the next Provenge or another headstone in the R&D graveyard. But there is no doubt that BioVex’s investors were offered a deal that was simply too good to pass up.
|NCT IDs||Malignant melanoma||NCT00769704|
|Head and neck cancer||NCT01161498|