Kite: New National Cancer Inst. study just publi

Geez, am I the only one who picked up on the National Cancer Institute study just published, with great results for Kite?

http://seekingalpha.com/news/3251274-nci-led-study-treatment…

My notes below:

National Cancer Institute study in treatment-resistant non-Hodgkins lymphoma builds on successful ZUMA-1 study of axicabtagene ciloleucel by showing durability of response.

National Cancer Institute led study assessing a single dose of anti-CD19 CAR T-cell therapy in 22 patients with refractory or relapsed non-Hodgkin lymphoma (NHL). The data were just published in the Journal of Clinical Oncology.

Objective response (OR) rate was 73% (n=16/22)
Complete response (CR) rate was 55% (n=12/22).

Duration of responses ranged from more than seven months to more than 24 months, with 11 of 12 (92%) complete responders still ongoing.

Reversible grade 3 (severe) or grade 4 (life-threatening) neurotoxicity was observed in 55% (n=12/22) of treated patients.

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Saul,

I hate to break it to you, but this is not a terribly positive study for Kite.

55% grade 3/4 neurotoxic events??? … all of them went on to have a spinal tap, with a median number of 22 WBC’s (>5 and we in the ER call you meningitis and likely admit you to the ICU!). 3 of the 22 ended up with “a short course of vasopressors” - they act like that’s a benign thing! These patients require a central line and an ICU admission. There is not a provider in the world that can or is willing to differentiate the hypotensive, altered, febrile (aka SUPER-FREAKING-SICK) chemo patient from having severe critical illness to “just a chemo reaction.” Oh, and another two were put on a ventilator! Thats ~20% of their patients that had at least a 2 day ICU stay, if not more!

febrile neutropenia??? with a new chemo agent? I highly doubt there are many hospitals that are discharging those patients home from the ED.

There were also 2 patients with notable delayed events, one with myelodysplasic syndrome, and another with vision loss. both not attributed to their drug, but something to monitor.

I like that they have a test to gauge the efficiency of their drug (IL-15). That helps. But they changed their chemo doses midway through testing this drug -that’s a big no-no. This is a trial on a whole 19 patients with diffuse large B-cell lymphoma, two with follicular lymphoma, and one with mantle cell lymphoma.

This is a life saver for about 10% of patients, and a nightmare / torture device for the others. There are incredible safety issues with this drug which - in its current form- will limit it to those hoping for a miracle and willing to deal with a rocky post-treatment course. It will also be hard to expand indications to other illnesses with this sort of safety profile.

I’ll pass.

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22 patients is a very small study group. And high side effects.

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Completely concur guys - it doesn’t have the makings of decent trial outcome (in terms of size, design, control and result) and I can imagine Real World Evidence uncovering substantial negative backwash with more data (clinical and economic).
Ant

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The side effect profile fits more along the lines of a bone marrow transplant than standard chemotherapy. Marrow transplantation is an accepted treatment but its use is limited because of its risks.

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The people in this trial (and all the other NHL/AML CAR-T) have an average lifespan of 4-6 months from when they enter the trail and have failed multiple (usually 3to5 harsh chemo regimens). So if you have a 55% chance of complete remission at 7 months (prior studies show CR at 6 months has a high 90%+ correlation w/ long term survival) you might want this CAR-T. It is not a no risk option, but it is what most oncologist and patients would take when that’s the hand your dealt vs doing current treatment option #4,5 or 6. You may want to read watch how effective and side effect heavy 3rd, 4th, 5th line treatments are for relapsing NHL.

Also keep in mind that the 2nd generation CAR-T (almost every company I know about has this in the next 1-3 year studies) has a on/off switch to ameliorate the neurotoxicity and cytokines release syndrome. When this happens, CART treatments will be done 1st and 2nd line (at least in trials) to see if they will replace standard of care. That probably is 3-5 years away.

This is the early stages of the immunooncology, ‘the 1st inning’. So if you are happy with the quick gains great. It will be volatile. So if the FDA delays KITE Cd19 cart, then it will probably get cut 50%. If they approve it will likely go significantly higher. Either way it is likely to be volatile.

Lastly from a long term prospective, the company that gets treatment for solid tumor right and maybe cheapest will win. So if you want to follow this space, follow ADAP/BLCM, CLLS, ZIOP, NK, JUNO to name a few. Genetic testing is now very cheap. So the IP that will be developed in the next 3-5 years will put some of the biotechs is a great position. But if you want to stay in the sidelines, you are in good company Gilead’s CEO recently said they are staying on the sides for now b/c cost concerns.

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So why isn’t KITE stock price being hit on this negative news

This seems to be the kind of news that could bring the price back down to earth.

I still say that for anyone that has enjoyed this runup you need to at least take part of your winnings off the table, otherwise you are just a gambler.

Chris

* Kite Pharma Inc : Jefferies raises target price to $101 from $82; rating buy

You may want to read up on what happened with Dendreon & Provenge before continuing to invest in the Kite fairytale. Kite is in an eerily similar situation to DNDN with a similar drug.

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I hate to break it to you, but this is not a terribly positive study for Kite.

Hey Fuma, I hope you are not short the stock as it’s up again today, but I think you are missing the point. These were 22 patients with a death sentence, for whom nothing had worked, refractory to treatment, and all the rest. “No Hope” patients!

Out of the 22 No Hope patients, 12, or
55% of them had a TOTAL REMISSION !!!
55% of hopeless patients had a FULL REMISSION !!!
Which is still ongoing for 92% of those 12 full responders (11 of them) !!!
Up to 24 months later !!!
And you think that’s not a good result?

I’d guess that if some of them had to spend 3-5 days in a hospital being sick as a dog, they’d figure that was a very, very, very, VERY, small price to pay. They were going to die before this treatment came along, for goodness sake!

Just the way I see it.

Saul

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Thanks for the update Saul.
Obviously from the reaction today more people agree with your analysis then not.

Chris

People will go through almost anything to stay alive. Even treatments and procedures with a relatively high risk of morbidity. Given that some (or all?) of these patients had had a bone marrow transplant before, they’ve been through a similar type of procedure.

Of course 45% of these patients’ deaths may have been hastened by the treatment, or their final days made significantly worse than they could have been.

Assuming FDA approval, with no caveats, success will still require good marketing, teaching oncologists/hospitals, and lobbying for reimbursement.

Fuma has a good point in pointing out Provenge. I think Tinker followed DNDN pretty closely back in the day on the NPI board.

In KITE’s favor, it’s typically bad PR to deny treatment to cancer patients, especially ones that are often fairly young and look ill.

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I have no dog in this race, merely trying to look out for fellow Fools. I’ve watched biotechs like this come and go for just over 15 years and hoping to prevent you from making some of my mistakes.

-this treatment has not been compared to anything, so how do we know its any better than snake oil? The clinical trial arena is littered with instances where the placebo arm fared much better than historical controls and hamstrung the treatment arm.
-they changed the dosage of the chemo regimen between the first and second trial (as well as during the second trial) which significantly reduces likelihood of FDA approval.
-because of this, even if approved, its anyone’s guess what a treatment dosage would look like - no one knows what optimal dosing is yet.
-novel mechanisms fail FDA approval 70% of the time & twice as often.

-even if approved (likely <10%), safety profile will significantly hinder expansion of its label in an already very narrow market.

-somewhere between 30-70% of these patients will be ICU admits based on KITE’s previously documented ADR rates.
-1 year survival after ICU admission for those >85 years of age is 3%
-1 year survival rates after ICU admission rates for all comers is about 30%

There are stumbling blocks at every corner for KITE to be successful. In addition to the FDA, will KITE be able to produce the drug in a timely manner? This will be insanely expensive to produce - likely in the realm of 200k+ / treatment. Insurance companies will also more than likely have an ICU bill. Stop being a humanitarian for just one minute and ask yourself- why do we think insurance companies would pay for this? If your answer is because “life is invaluable” then you likely have not had much interaction with insurance companies before. Do we think they’ll pay for a treatment with questionable efficacy and tons of ADRs that will generate additional big bills?

I’d love to see this drug work, unfortunately it doesnt look like it works well. If you invest now, there is a real chance you lose 60%+ overnight. Even if they get FDA approval, they are going to need additional funds, and they will have manufacturing & sales / insurance company reimbursement issues to overcome. You can wait and see how this plays out, and if the smoke clears abit, you can still make a good bit of money with much less attached risk.

IMHO, invest in KITE only if you are willing to part with your investment almost overnight.

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Fuma,
I’m attrmeptng to learn about KITE, not yet invested in it. I’m always skeptical, but that’s my business sense. Admittedly I know very little about science and medicine so it usually keeps me out of these types of investments. In fact if I had bought say at 40, I’d be selling at least half my shares at these levels.

That said here is where I see your post stumbling for me.

I was very hooked by your knowledge, your points are all well taken and you seem to have a good deal of knowledge about this space. Reading your post, I feel like I’ve really learned something.

The problem I have is that you state that an investor needs to sell now or risk losing most of their money overnight. I’m not sure why you needed to make that statement.

For me, your post went from a great argument for being very careful and understanding in detail about the risks of being a shareholder in KITE, to a short seller trying to get the stock to go down tomorrow.

Again great points, I’m just wondering it you are also motivated in seeing the stock price tank.

Chris

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-1 year survival after ICU admission for those >85 years of age is 3%
-1 year survival rates after ICU admission rates for all comers is about 30%

Not sure where those stats come from, but they seemed to be low and hopefully not just “alternative facts” offered for dramatic effect.

A quick pubmed search revealed:

1 year MORTALITY after ICU admit in a Dutch study of 91,000 patients was 12.5%. Suggesting SURVIVAL was 87.5%.
https://www.ncbi.nlm.nih.gov/pubmed/23591209

Other studies quote around 30% MORTALITY. Still 70% survive.

1 year SURVIVAL for those over age 80 in another study was 41%. Still not great, but better than the 3% mentioned.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4456598/

I’m not here to take any sides in this debate, but wanted to offer some alternative numbers. If anything, I’d probably gravitate toward Fuma102’s message of caution. I don’t personally invest in biotech/pharma because of the often binary outcomes. Though perhaps a small position that won’t hurt if goes to zero and may help move the needle if goes to the moon may be a way to responsibly play in this arena.

Good luck to all,

Jeff

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Thanks Fuma, for your take on KITE.

I was starting to consider an investment, but after reading your cautionary posts, I think I’ll sit this one out (especially at current price point after large gain).

Chris, I didn’t take his point about it dropping 60% overnight as him saying that was going to happen tomorrow, I took it to mean that at some time in the future, there’s a pretty good chance that a large drop could happen. And I realized, that I agree with this, and don’t want to take that gamble on getting in/out at the right time to avoid it.

I have many other less risky alternatives I will put my money in for now, and admittedly, probably not as potentially rewarding as this one, either.

I also did not take Fuma’s caution of losing 60% overnight as a scare tactic. I have no position in KITE, but also offered the same experience. I haven’t been watching biotech for 15 years like Fuma, but just in the last 18 months I’ve seen MANY that do drop significantly overnight from a single phase 1 or 2 or 3 test result. It’s just the nature of the sector.

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A 60% drop on a negative trial result or FDA knock back is a very real possibility and there are tons of data on this. (Just as there are tons of data on the 100+% uplift on approvals which penny share newsletters keep touting.)

I view this as a total gamble.

It’s not as though they have a profitable portfolio to fall back on.

This is binary options trading.

Once I would have been seduced by the story but not now. (Getting old and perhaps 20 years in life science has something to do with it).

Ant

Well both of you nay not have taken it that way, but possibly because both of you are not invested? How would you take a statement “the stock will drop 60% overnight” if you had say 10k or more at stake.

I’m not invested, but I see how that could send a bit of a chill down an investors neck.

I like the way both of you worded it better and I agree.

Much better to say “I think there is the risk of the stock price being cut in half if my thesis is correct going forward”.

Ok, then from there looking at this posters data, how much of that data is actually correct.
Seems like a couple of points have already been challenged.

So yes I agree, caution is needed when investing on hot stocks like these. All I can see is a flip of a coin going forward, which means we could also go up 60% overnight, but I don’t see that as a reality either.

On the sidelines.

Chris

Chris, while there is a lot of that sort of thing going around … i.e., shorts spreading bad news, real or not to tank a stock … Fuma is hardly that sort of person. On the contrary, it is his field of expertise and he is sharing a perspective. Anyone who has been around biotech for any time has the experience of seeing some incredibly promising treatment turn out to not work in larger groups or to have nasty side-effects which make usage questionable or which turn out not to be approved … often for good reason. Biotech is like that … very high risk and occasional high reward. This could be one that makes it … and it is certainly interesting … but there are a lot of warning signs that one should be paying attention to before diving head first into that pool.

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