March 17, 2014

" of...biotech's top prospects."

Note: I've edited and completely taken out of context a sentence from FierceBiotech's John Carroll's March 15 article Amgen's viral cancer vaccine T-Vec tackles melanoma tumors in PhIII. The full uncorrupted sentence is "While cancer vaccines have had a poor track record in the clinic in recent years, Amgen has tapped T-Vec as one of the big biotech's top prospects."

  • Dr. Roger M. Perlmutter, M.D., Ph.D., formerly of Amgen, now Merck's Executive Vice President and President of Merck Research Laboratories, convinces Amgen to buy BioVex in 2011 for $1 billion to gain access to T-Vec or talimogene laherparepvec, formerly OncoVEX, and
  • T-Vec is one of B's top prospects in 2014, according to FierceBiotech, considering Amgen's acquisition of Onyx Pharmaceuticals in 2013 for $10 billion to gain access to Nexavar or sorafenib and Krypolis, and
  • Perlmutter convinces Merck to combine anti-PD-1 agent MK-3475 or lambrolizumab with T-Vec for previously untreated advanced (metastatic) melanoma as well as drugs from Pfizer and Incyte, and
  • Dr. Robert H.I. Andtbacka, M.D.,  who is a lead principal investigator on T-Vec's Phase 3 trial, routinely presents a table showing PV-10 very likely is significantly better than T-Vec for injected, non-injected and non-injected systemic lesions/tumors, and
Comparison of respective per-subject Phase 2 single-arm trials
  • PV-10 should be a top biotech prospect too, and
  • PV-10 (value) > T-Vec (value).
Interestingly, 5-6 years after presumably final metastatic melanoma ("MM") Phase 2 trial results for T-Vec, Amgen/BioVex publishes a tumor analysis of this study. BioVex management designed their Phase 3 trial with survival-based endpoints, meeting them for the trial's interim analysis (Vical's Allovectin-7 failed to meet its overall survival endpoints). Provectus pursued survival-based endpoints and a special protocol assessment for a pivotal MM Phase 3 trial until they convinced the FDA tumor-based were more appropriate for locally advanced melanoma. It would strike me Provectus was ahead of the curve in focusing the Agency on the applicability of tumor-based endpoints for intralesional agents like PV-10 and their applicability to locally advanced melanoma. It would strike me Amgen (Dr. Andtbacka) is catching on through the completion of this variation of the Big Biotech's study analysis.

In Amgen's "tumor study," "Of the 295 patients treated with talimogene laherparepvec, almost 4,000 tumor lesions were tracked for this analysis. Half of these lesions were injected with talimogene laherparepvec at least once, while the rest were not injected, including visceral tumor lesions (tumors involving solid organs such as the lungs and liver). The results showed a 50 percent or greater reduction in tumor size in 64 percent of injected tumors. In addition, one-third of uninjected non-visceral tumors, and 15 percent of visceral tumors were also reduced by at least 50 percent. There were 35 melanoma-related surgeries performed during this trial of which 30 percent successfully removed all residual disease."

I cannot do a general comparison of the two because there is not sufficient publicly available PV-10 data, but I tried to construct what I could from the readily available information.
Click to enlarge the table
A couple of things jump out:
  • While Amgen's poster may elucidate this, there is no mention (or breakdown) in the press release or SSO 2014 abstract about complete response.
  • T-Vec's results are from a Phase 3 trial whose treatment protocol presumably is what would be used in the clinic, while PV-10's results are from a Phase 2 trial using a limited treatment protocol.
Notably, however, there is durability of response data for T-Vec: "This new analysis is built on a study that recently demonstrated a durable tumor response of at least 6 months in Phase III. And interim results from another study concluded that T-Vec patients had a median overall survival rate of 23.3 months compared to the 19-month average posted by patients treated only with GM-CSF" (Source: previously linked FierceBiotech article on Amgen and T-Vec). The other T-Vec study referred to above is BioVex's MM Phase 2 trial. Provectus management has not yet released durability data from its MM Phase 2 trial for PV-10, although previously released progression free survival data does provide somewhat of a facsimile.

Additionally, the Reuters article on the T-Vec work was revealing, given the Amgen's executive careful verbiage: "...its potential ability to  stimulate a systemic anti-tumor immune response." {Emphasis is mine}

No comments:

Post a Comment