Glybera is safe for now. With the unequivocal failure of Vical’s Allovectin, UniQure Pharma’s lipoprotein lipase deficiency treatment will remain the only gene therapy to have gained regulatory approval in the western world for some time to come.
To its credit Vical made no attempt to raise hopes of a positive future subgroup analysis, and stated clearly that Allovectin – its lead project – would be terminated as it switched focus to anti-infective vaccines. Far more surprising was the group’s insistence that it had run a well-designed phase III study.
In fact, the trial, adding Allovectin on top of dacarbazine and temozolomide in 375 stage 3 and 4 melanoma patients, suffered from several flaws, including that it excluded the most advanced patients, such as those with brain or liver metastases, or those with tumours above 10cm x 10cm in size.
Moreover, Allovectin had become largely irrelevant in melanoma. Recent newcomers Bristol-Myers Squibb’s Yervoy, Roche’s Zelboraf and GlaxoSmithKline’s Tafinlar and Mekinist have squeezed the market opportunity, and excitement in the space was being generated by PD-1 antibodies and not risky gene therapies.
The phase III trial was an extremely long shot, previous data having come only from single-arm studies, and given Vical’s sub-$300m market capitalisation and failure to sign a major licensee for Allovectin failure seemed assured (Event – Vical trial another test of cancer gene therapy, May 7, 2013).
Moreover, there were earlier hints that all was not well: study readout had been delayed because patients were not dying as quickly as had been expected – an indication that an insufficiently advanced population had been recruited. The warning signs notwithstanding, Vical’s stock still plummeted 57% yesterday, and the California-based biotech is now valued at a mere $132m.
Vical said that Allovectin, a lipid-plasmid complex encoding the HLA-B7 and beta-2 microglobulin genes, had failed to show a benefit in either objective response or the more important secondary measure of overall survival, without providing numerical data. It called the result “very deeply disappointing”, and said the data were clear and conclusive, with no margin for another interpretation and no feasible path forward.
The company can at least take some relief in the fact that the failed study had been funded by its Asia partner AnGes. It will now turn its attention to a portfolio of infectious disease vaccines, the most advanced of which is ASP0113, a phase III cytomegalovirus project licensed to Astellas Pharma.
Nothing to do with tech?
Vical is now heavily touting some of the early data it has seen with this pipeline, and says Allovectin’s failure had nothing to do with its DNA technology.
One fact sticks out like a sore thumb, however: this technology is 24 years in the making without scoring a commercial success. Nevertheless Vical has ruled out winding up and handing its $64m of second-quarter cash back to investors, insisting that vaccines based on its Vaxfectin adjuvant, for instance, were “very partnerable”.
Licensing talks on Allovectin had apparently taken place with big pharma companies, but no deal was ever struck. Astute observers of the abysmal track record of unpartnered phase III oncology projects held by companies with a market cap of $300m or less will have already taken note of Vical’s inability to do a deal (Ten oncology companies to avoid, February 14, 2013).
Willing investors now have to take a punt on Vical’s anti-infective vaccine strategy and believe that the relative inactivity of this pipeline is merely a reflection of it having taken a back seat to Allovectin.
A significant deal needs to materialise soon.
|Indication||Study design||Trial ID|
|Melanoma||375 patients given Allovectin + DTIC + TMZ, versus DTIC + TMZ alone||NCT00395070|