[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investment ideas. His ideas, thoughts and words are his own, and you can see all his past pieces here.]
A projected winner hits a snag
No sooner had the Doc Gumshoe dossier about the 2017 FDA approvals posted than a bit of bad news surfaced about one of those winners. AstraZeneca’s Imfinzi (durvalumab) was approved for the treatment of urothelial carcinoma (an advanced form of bladder cancer), and was projected to bring in about $2.8 billion. Imfinzi was being evaluated in a Phase 1 / 2 study as part of combination therapy in HPV-associated cancers with a new agent from Advaxis, axalimogene filolisbac. The short take version (and I did promise short takes, didn’t I?) is that after five doses of the combined therapy, which went just fine, a patient with advanced refractory metastatic cervical cancer developed respiratory failure while receiving the sixth dose. Despite efforts to reverse her worsening condition, the patient died.
Based on previous data in studies with Imfinzi, it seems somewhat likely that the cause of the patient’s respiratory failure and death was Imfinzi and not the Advaxis agent. One patient in AstraZeneca’s Phase 3 trial of Imfinzi in lung cancer had died of respiratory failure. That, by itself, should not be definitive proof that Imfinzi was the cause of death; the patient, after all, did have lung cancer.
In any case, the FDA stopped the Advaxis combo trial, and at this point they’re trying to figure out what to do next. The Advaxis agent, axalimogene filolisbac, is a proposed cancer vaccine based on Listeria monocytogenes, a bacterium that can cause meningitis in susceptible individuals, mostly immunocompromised children and the elderly. (Needless to say, the bacterium is modified so as to be relatively harmless.) The Listeria bacterium is taken up by cells that are active in the human immune system such as phagocytes, and can induce both CD4 and CD8 antigen-specific immune response. Thus, it is a promising candidate as a cancer-vaccine vector.
Whether this incident has any major implications for Imfinzi remains to be seen. However, this is an illustration of the perils that pharmaceutical outfits run even after FDA approval. It is usual that a pharmaceutical company would look for other indications after a drug had been initially approved in a fairly narrow slot. This is particularly the case with cancer drugs, which typically – these days, anyhow – get approval with very narrow indications such as relapsed or refractory cancers with a specific genetic footprint. But the hunt for broader indications has its risks.
(As we’ve discussed in previous installments, the only way a prospective cancer drug could gain approval for a broad indication such as solid tumors would be to go up against an established drug in a head-to-head trial and be shown to be superior. That would be hugely risky for the prospective candidate, and the FDA would be highly unlikely to approve a trial where half the patients got an untried drug when an established drug is available.)
More about oncolytic viruses
The term “oncolytic viruses” is, all by itself, an expression of optimism. The “onco” part refers to tumors, and the “lytic” to lysis, or dissolution. An oncolytic virus is thus, by this optimistic definition, a virus that dissolves tumors. Are there any such?
The answer is an unequivocal “Yes!” The first FDA-approved oncolytic virus was Imlygic (talimogene laherparepvec), from Amgen, which got its seal of approval on October 27, 2015, with, as is usually the case, a fairly narrow indication: “Indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.”
It has been known for some time that some viruses preferentially attack cancer cells rather than normal tissue, but this by itself does not make even those viruses into ready-for-action cancer fighters. Even those viruses are likely also to infect normal tissue. As a rule, viruses need to be genetically modified such that they attack tumors while leaving the human host unharmed. Imlygic is such a virus. It is a ge