Almost only counts with horseshoes and hand grenades, as the saying goes. Certainly when it comes to oncology clinical trials coming close to hitting an overall survival endpoint is just not good enough.
By missing, albeit narrowly, the chance to show a survival benefit in metastatic melanoma Amgen’s talimogene laherparepvec, also called T-Vec, now faces limited sales and an almost certain future as a combination product – if it gets approved.
Last week, the biotech giant reported phase III trial results for T-Vec that pitched it against white blood cell growth factor GM-CSF, and showed a p value of 0.051 for overall survival (OS).
Few had been expecting spectacular results for the project, but in an era where survival benefit is king the regulatory risk has increased. And in an already competitive field T-Vec’s potential to make significant sales will be greatly reduced (Upcoming events: Phase III confirmation for Amgen's T-Vec and Otsuka's brexpiprazole, February 21, 2014).
Add this to a mode of administration that relies on injecting the oncolytic virus directly into tumours and EvaluatePharma's modest sales forecasts of $92m in 2018 are unlikely to climb much higher. All of this will be a disappointment for Amgen, which back in 2011 bought BioVex for $425m essentially to acquire T-Vec, with the promise of future milestones of up to $575m.
But back then the project was dazzling with phase II results that showed impressive tumour shrinkage rates and complete remissions, giving hope that oncolytic viruses might be the way forward. However, T-Vec still remains the most advanced project in the class, and according to EvaluatePharma there are only seven others in phase II, none of which has managed to secure a big pharma partner.
Not only has T-Vec failed to live up to its promise in melanoma in larger trials, it is rapidly being eclipsed by the PD-1 inhibitor class and various combinations. Such are the hopes for these projects that in 2018 Merck & Co’s MK-3475 is expected to bank $2.79bn, while Bristol-Myers Squibb's nivolumab is forecast to pull in $4.15bn, according to EvaluatePharma.
Luckily for Amgen, T-Vec was one project that Merck chose to twin with MK-3475 in the combination studies it announced earlier this year (Merck tries to climb back into PD-1 combo race, February 6, 2014). But the first results from this phase II trial are not expected to read out until 2016.
Slightly nearer-term excitement might be provided by the results of the T-Vec/Yervoy combination, which could have results by December 2015.
Going it alone
Amgen might also plough on with T-Vec monotherapy and, as ever with disappointing results, hope has already been found in subgroup analyses. An interim look at the data in November revealed possible efficacy not only as first-line therapy, but also in patients with stage III or IV/M1a disease.
While there was no update on the subgroups this time around, Amgen did say that the interim median OS benefit of 4.3 months had remained broadly similar. The big reveal of the full data is expected at Asco and should give greater clarity on whether T-Vec will have a decent future on its own.
But T-Vec's less-than-stunning form and the fact that oncolytic viruses have yet to prove themselves convincingly, the project's potential might be limited to a supporting act for some of the bigger oncology superstars in the market.
|T-Vec compared with GM-CSF||NCT00769704|