BOSTON (TheStreet) -- Thank you in advance for reading the latest Biotech Stock Mailbag. This week, I tackle questions about cancer drugs from Bristol-Myers Squibb (BMY - Get Report) , Exelixis (EXEL - Get Report) and Lion Biotechnologies (LBIO) . Also covered: GW Pharma (GWPH) , Rockwell Medical (RMTI - Get Report) and Genfit (GNFTF) .
Earlier this week, Bristol-Myers Squibb announced the U.S. Food and Drug Administration granted Breakthrough Therapy Designation to Opdivo for the treatment of advanced renal cell (kidney) cancer.
This is certainly good news for Bristol, but not much a surprise given that a phase III study in previously treated kidney cancer was stopped early in July following an interim analysis demonstrating a survival benefit for Opdivo over Afinitor (everolimus), the current standard of care for second-line kidney cancer patients.
Full results from this Bristol study, known as Checkmate-025, are being presented on Sept. 26 at the 2015 European Cancer Congress. Bristol has already announced plans to submit Opdivo for approval in second-line kidney cancer this year. If approved, Opdivo will be the first checkpoint inhibitor therapy for kidney cancer patients. Opdivo is already approved for melanoma and non-small cell lung cancer.
Novartis (NVS - Get Report) secured U.S. approval for Afinitor in second-line kidney cancer based on a study demonstrating a 67% reduction in the risk of disease progression or death compared to placebo. At the median, Afinitor progression-free survival (PFS) was 4.9 months compared to 1.9 months for placebo. Keep these data in mind for the Opdivo Checkmate-025 data presentation next week.
At next week's European Cancer Congress, investors will also compare the Opdivo kidney cancer data against a presentation of results from Exelixis' phase III "METEOR" study of Cometriq. In July, Exelixis announced that Cometriq reduced the risk of disease progression or death by 42% compared to Afinitor in second-line kidney cancer patients. Cometriq also demonstrated a non-significant 33% reduction in the risk of death compared to Afinitor (with survival data still maturing and subject to change.) Full details from the METEOR study are being presented on Sept. 26.
Exelixis plans to seek approval for Cometriq in second-line kidney cancer early next year, setting up a potential for doctors to have two new treatment options.
Investors don't often get the opportunity to compare two large studies of different cancer drugs in the same patient population, especially when the the same drug is used as the comparator in both studies. The Opdivo and Cometriq presentations next week should generate a good deal of attention.
My general view of "proof of concept" clinical trials is that the promoted results (usually via an optimistically penned press release) are like the people at Lake Wobegon -- strong, good looking and above average. Drug companies design proof-of-concept studies to find something positive about whatever drug is being investigated.
This is not to say all proof-of-concept studies are B.S. You just shouldn't get too excited about them.
Unsurprisingly, GW Pharma said this week that cannabidiol (CBD) demonstrated superiority over placebo across a series of "exploratory endpoints" used to measure efficacy in schizophrenia patients not responding to first-line antipsychotics.
"As a phase 2a proof of concept study, there was no single primary endpoint, but a series of exploratory endpoints," said GW Pharma in its press release announcing the cannabidiol results.
In other words, a can't-miss study design. Cannabidiol may benefit schizophrenia patients. I just wouldn't pencil in revenue yet.
The more relevant clinical catalyst for GW Pharma are the results from the phase III studies of Epidiolex (CBD) in childhood epilepsy, expected in the first quarter next year. I have not dug into the previous Epidiolex data so I'm not in a position to handicap the outcome phase III studies. I will say this: I have friends in California with a severely mentally handicapped son who has suffered from life-threatening seizures his entire life. They have tried just about everything to control their son's seizures. No treatment has been more effective than the CBD oil they make themselves from genetically altered marijuana plants grown in their backyard.
Anecdotal evidence? Absolutely, but it also bodes well for the outcome of GW Pharma's Epidiolex studies.
Lion Biotechnologies is developing cancer immunotherapies based on tumor-infiltrating lymphocytes (TILs.) TILs are a type of immune cell which target and try to kill young cancer cells. Unfortunately, the TIL attack is usually blunted because growing cancer cells have devised ways to hide from or suppress the immune system.
Based on the work of government researchers, Lion is trying to develop personalized, super-charged TILs capable of defeating the immunosuppressive capabilities of cancer cells. Here's how it works: First, a patient's tumor is removed surgically, from which TILs are isolated. The TILs are then taken to a lab where they're grown into the billions without being exposed to any immune-suppressing signals from the tumor. The more powerful TILs are then re-injected back into the patient to seek out and kill cancer cells.
(In case you're wondering, TILs and CAR-T are both considered cellular cancer immunotherapies. The difference is that TILs are immune cells grown in a lab but otherwise unmodified where the immune cells used in CAR-T are reconstructed to add a receptor on their surface to better identify cancer cells.)
On Wednesday, Lion announced an update from a National Cancer Institute-run phase II study of TIL therapy in metastatic melanoma patients. The results were not all that different from previous disclosures but were still very encouraging. Patients enrolled into this study have melanoma no longer responding to multiple prior therapies, including checkpoint inhibitors like Bristol's Opdivo or Merck's Keytruda. Treatment with a personalized TIL therapy plus the immune-system boosting drug IL-2 resulted in a 54% overall response rate. Twenty-four percent of patients achieved a complete response which was durable. Overall survival was approximately 80% at 12 months.
Lion shares dipped when the updated TIL data were announced Wednesday afternoon. The stock eventually rebounded and closed higher but is down again Thursday as I write this column.
The muted investor reaction is probably due to the fact that Wednesday's TIL data were not all that different from what was previously presented. There's also significant uncertainty about where TIL therapy might fit into the rapidly evolving treatment of cancer. Like CAR-Ts, the manufacturing process required to produce a TIL therapy is complicated and expensive.
If eventually approved, TIL therapy might be restricted initially to patients who no longer respond to any other therapies, including checkpoint inhibitors. Given all the negative attention on the high cost of cancer drugs, it's not clear if TIL therapy, again like CAR-T, can justify high costs enough to be commercially viable products.
One more wrinkle to think about: The TIL therapy data look great, so far, but there's looming competition from combinations of cancer immunotherapy drugs and new technologies, including bi-specific antibodies. At this point, it's almost impossible to pick a winner.
Oh, and one last thing, promise: Lion's management team operates from deep inside Wall Street's credibility penalty box. These are not the most trusted guys, to put it mildly.
@adamfeuerstein: Is Triferic going to launch worse than Auryxia? Market just crushes slow launches.— Donny (@41NAS) September 16, 2015
Yes, Rockwell Medical's commercial launch of Triferic will disappoint. Worse than Keryx Pharma's (KERX) Auryxia? I'm not sure. It's hard to launch worse than Auryxia but I'm confident Triferic will run into similar problems -- limited access to dialysis clinics and reimbursement hurdles.
Genfit's delinquent elafibranor (GFT505) deadlines are more significant than this week's announcement from the company about the development of blood test to possibly diagnose non-alcoholic steatohepatitis (NASH.) I say "possibly" because Genfit's press release was scant on details about its new NASH diagnostic. Without outside validation and regulatory approval, Genfit will still need to rely on liver biopsies to confirm NASH diagnoses and measure the endpoints of its planned phase III study. (Genfit did say the blood test will also be used in the phase III study.)
About that elafibranor phase III study in NASH, investors are still waiting to hear from Genfit about the outcome of planned meetings with U.S. and European regulators. Those meetings, needed to finalize the NASH phase III study design, were supposed to take place this summer. Genfit also told investors to expect a publication of the elafibranor NASH phase II study results this summer. So far, nothing.
A Genfit spokesman told me the company is still on track to start the phase III study before the end of the year. A phase III study from NASH competitor Intercept Pharmaceuticals (ICPT - Get Report) is already underway.