Welcome to your weekly digest of approaching regulatory and clinical readouts. The FDA is soon to make approval decisions on two potential cancer treatments: Amgen’s oncolytic virus immunotherapy T-Vec in melanoma and Merrimack’s pancreatic cancer contender MM-398.
Both projects look likely to get the go-ahead, but would face hurdles in the market. A big challenge for Amgen will be carving out a niche for T-Vec, which has been eclipsed by the likes of Opdivo and Keytruda.
Time for T-Vec
T-Vec (talimogene laherparepvec), which has a PDUFA decision date of October 27, has already received a 22-1 endorsement from an advisory panel, making its approval all but assured (Adcom puts T-Vec on track to underwhelm, April 30, 2015).
But it will probably be of more importance as a landmark in the field – as the first approval of an oncolytic virus in the western world – than in the treatment of melanoma, where new therapies, notably checkpoint inhibitors, have made a major impact.
This is reflected in analyst forecasts, with T-Vec’s 2020 sales expected to hit just $149m according to EvaluatePharma’s consensus.
One potential snag is that approval might come in a narrower indication than Amgen would like. The FDA requested a three-month delay to consider additional data and the correct population for the drug will surely have been one of the things under discussion.
The results supporting T-Vec’s application are somewhat controversial: although the Optim phase III study met its primary endpoint, by showing an extension of the durable response rate, subsequent data showed an arguable miss on overall survival, and asymnmetric dropouts were a key concern. Furthermore, the control arm was GM-CSF, which is an immuno-stimulant and not approved for melanoma.
There are also practical issues that could hinder uptake, not least that T-Vec needs to be directly injected into tumours.
The way forward for T-Vec looks likely to be as part of a combination therapy. It is already being tested along with Merck & Co’s Keytruda in phase III in melanoma and in phase I in head and neck cancer, and with Bristol-Myers Squibb’s Yervoy in phase I/II in melanoma.
Amgen is also collaborating with Roche on a combo of T-Vec plus atezolizumab in triple-negative breast cancer and in colorectal cancer with liver metastases. But even if the results with these combos are positive it looks like T-Vec will still end up playing second fiddle to the PD-1/PD-L1 inhibitors.
Merrimack on fast track
A decision on Merrimack’s lead asset, MM-398, meanwhile, is expected by 24 October. The project, which has orphan, fast-track and priority review statuses, is being considered as a second-line treatment in patients with metastatic pancreatic cancer.
Again, approval is expected: the phase III Napoli-1 trial met its primary endpoint, showing a statistically significant improvement in overall survival – however, the increase was just 1.9 months over the control group, raising questions over clinical importance.
Even so, the data were enough to snare Baxter, albeit in a heavily back-loaded deal (Improbable Merrimack deal has a familiar sting, September 24, 2014). Baxter's subsequent spin-out Baxalta has rights outside the US; MM-398 is also awaiting approval in Europe.
On Merrimack’s side is the fact that there are limited options for second-line pancreatic cancer patients, which should help it get the thumbs-up from the FDA. Getting payers onside could be another story, especially amid current grumblings about drug pricing.
Merrimack is also trying to expand into first-line pancreatic cancer and should soon start enrolment in a phase II trial in untreated patients. In addition MM-398 is in phase I in breast cancer, paediatric sarcoma and high-grade glioma.
Targeting a broader patient population is likely Merrimack’s ultimate aim. Approval in the second-line pancreatic cancer setting could be the foot in the door that it needs.
|T-Vec||Keytruda with or without T-Vec in unresected melanoma||NCT02263508|
|T-Vec||Yervoy with or without T-Vec in unresected melanoma||NCT01740297|
|MM-398||MM-398 in 1st-line metastatic pancreatic adenocarcinoma||NCT02551991|