Hacker News Reader

> I think this is one example of the free market working well.

How so? While I'm sure the Mayo Clinic will be attempting to patent and license this therapy, the research was apparently funded by the US government and various philanthropies.

[Quoting relevant sections of the paper since the full text is paywalled.]

"Grant Support: This work was supported by funds from the National Institutes of Health/National Cancer Institute (grants R01CA125614 and R01CA168719), Al and Mary Agnes McQuinn, the Harold W. Siebens Foundation, and the Richard M. Schulze Family Foundation. The National Cancer Institute RAID (Rapid Access to Intervention Development) Program supported MV-NIS manufacture and toxicology/pharmacology studies.

Potential Competing Interests: Drs Russell, Federspiel, and Peng and Mayo Clinic have a financial interest in the technology used in this research."

I don't really know any hard numbers, but you have to imagine, getting this OV to market would be extremely expensive. Public funds only cover a small portion of the costs of the early research. Large scale phase 3 trials will be funded by the drug company expecting to profit off it.

If public funds and private donations could actually cover the research costs getting all the way to FDA approval, I would think you would see more doctors and researchers creating nonprofit partnerships to attract the funds and do the research. Sounds like it would be a dream come true to be funded to do research you cared about and better the lives of millions without the corporate suits getting in your way. But I think the reality is the facilities alone cost hundreds of millions if not billions, so just for Mayo to give you the lab space to work for a couple years is a major investment.

Public funds will end up paying for a large portion of those phase 3 trials because the biggest customer of the those drug companies will be government programs. If the trial is not successful that the government will still pay a large portion via increased prices for other drugs. (Plus there's forgone income via the extensive tax subsidies for health care spending.)

I don't know why we go through this kabuki process of pretending there is a functioning market in places where the government is such a dominant player (see also defense contractors). Why not just cut out the middleman?

I don't believe public funds pay for any large-scale, randomized Phase 3 trials in oncology -- the cost can rise above $100 million per trial! The overhead in terms of patient registration and follow up require the staffing, technology and expertise of a large pharmaceutical industry. And once that step is mandatory (again, in most large Phase 3 trials, exceptions made for pointed therapies like Gleevec), "the market" is necessary, functional or otherwise.

At this point I risk conflating not just two but three arms of the government: the NIH (funding), FDA (approval), and Medicare (payment).

> Why not just cut out the middleman?

Medicare has hinted at doing this, using its purchasing power to drive down the cost of drugs and refusing to pay for treatments approved to work but who have a low cost-to-efficacy ratio. A recent example is the fight over Hepatitis C medication[0]

[0] http://www.npr.org/blogs/health/2014/05/12/307747798/boomers...

Sometimes Walmart goes to a manufacture and says "We want to buy all of your output for the next 3 years, here's exactly how we want you to modify the product, and here's the quality assurance tests you need to do. Here's what we are going to pay." Walmart pays them some percentage up front and then over time as product ships and sells.

Is Walmart paying for the QA testing?

If I understand your analogy correctly, Walmart is Medicare, and the manufacturer is a drug company? If so, then said QA testing is not a guarantee; you cannot design a drug that will extend the lives of patients with end-stage cancer like you design a grill. It'd be like there was a government agency that compared the manufacturer's new grill to all other grills on the market, and only let the manufacturer sell theirs if it had a clearly defined benefit over the others.

I guess I didn't make my point clearly enough either time.

The government pays for the early research, sets all the ground rules for the drug trials, and -- as the drug companies' biggest customer -- ends up ultimately shouldering much of the cost of those trials whether successful or not. The government certainly has the financial wherewithal to fund stage 3 trials, $100M a pop is a rounding error on federal spending or even on just federal medical spending. So why not just go ahead and do so? Why the farce with pretending there's a healthy drug market when the government is driving so much of the process? Let's just admit this is a market failure of the public good variety, like firefighting and roads, and have the government provision it.

A solid point -- though the therapy is interesting on a novelty scale, the funding is decidedly vanilla. Grants fund the early research, patents are filed for novel findings, and if the therapy holds up eventually a large pharmaceutical firm will be necessary to perform the large scale trials.

Slightly tangential, but I wonder where the IP in this discovery is? If there is nothing to sell but injecting cancer patients with standard lab-grade measles, I think it is particularly open to being copied. Granted the measles used is genetically tweaked, but nothing I believe to enhance the therapeutic effectiveness.

My dad has been a MM patient for close to 6 years now and you are spot-on about the disease's general behaviour..

We started with Lenalidomide and was on it until end of last year with breaks of up to 6-8 months where there was no specific meds.. He's now on a Bortezomib cycle which will end in a couple of months and we hope to have some months free of meds again..

We never did the bone marrow transplant considering his age and stress/recovery he would have to go through.. MM is sympathetic in the sense that people who respond to meds can have a high quality of life even while undergoing treatment (my dad is still a practising medical Doctor). Lenalidomide is a tablet that you take at home while you go in once every week or two for Bortezomib shots.. The treatment is also considerably cheaper in India (still not inexpensive by any measure)..

The overarching fear for MM patients is the fact that its indeed incurable and how far/long we can go on before running out of treatment options.. Personally, seeing such trials and success gives us hope and comfort.. OV looks a promising approach and I hope my dad and others will be able to benefit from it..

Sorry to hear about your dad's illness. MM is a bitch.

If coming to the US is an option, there is a treatment center (Myeloma Institute for Research and Therapy MIRT) that is part of the University of Arkansas and is probably one of the best places in the world to get myeloma treatment. I know quite a number of people that have gone there and gotten good results.

It is based in Little Rock (of all unlikely places) I think because it was founded by a grant from Sam Walton, founder of WalMart. He died from MM in 1992.

> But did Washington Post forget to mention the 2nd patient they released data on, who didn't have any kind of prolonged response?

They mentioned the second patient in the article:

The trial included two patients. Russell said the treatment worked in Erholtz, whose tumors were mostly in her bone marrow. However, it was unsuccessful in the other patient, whose tumors were mainly in her leg muscles, the Star-Tribune reported. He said more research is needed to know how the nature of the tumor affects the virus.

wait, what? I'm not an oncologist but I read that muscles are the one tissue or place in our body which does not get cancer - this has to do with the way muscles are so 'greedy' for blood vessels that they do not allow angiogenesis to cancer cells.

Sadly not: http://en.wikipedia.org/wiki/Sarcoma

In the video at the mayo clinic site they talk a bit more about patient 2. While not all tumors were destroyed, they were fully mapped due to compounds from the thyroid being attached to the virus, implying that localized treatment would then be possible.

http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...

Editorial Article: http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...

Here's the full text I found: http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...

All haematological cancers are everywhere. The bizarre thing is, despite their outrageously disseminated nature, many haematological cancers now have amongst the best prognoses (at least in certain age groups).

> But these OVs are one-time deals. So a single dose treatment is a very interesting alternative. The only problem is, MM is extremely resilient, and the cells are everywhere. It's so hard to eradicate, unless the OV is a cure, it's just another tool in the box to manage MM and extend lives.

Yes, the key point to watch next is to see if the MM does not come back after a couple of years.

The virus is gone from her system. The MM is not at undetectable levels. So unfortunately, this OV is not a cure. This particular patient, her MM cells aren't surging just yet.

I think the curative approach will ultimately come from immunotherapy, training the body to attack the cells. OV could certainly have it's place, for example as an alternative to ASCT.

>I think the curative approach will ultimately come from immunotherapy, training the body to attack the cells.

As i know, just killing the cancer cells is not enough. The real curative treatment is to kill cancer stem cells using drugs.

http://www.survivingmesothelioma.com/news/view.asp?ID=001532

One thing I don't understand is this attitude of "well we can't detect it, so job is done". I don't know the specifics of detectability, but presumably it means that n<N for some N. So there could still be some cells left. Why not throw every weapon in the arsenal at them, to ensure the cancer is completely gone?

EDIT, addendum: If you have a few treatments that each can kill 9999/10000 cancer cells. It seems the current approach is apply treatment a. Not detectable yay! They grow back to original numbers. Apply treatment b! etc. If you did them all at once, they wouldn't have time to grow back in-between treatments giving a larger chance you get them all.

Because some weapons in the arsenal will be killing the patient as well as killing any possible cancer cells.

At some point the risks of the treatments outweigh the risks of leaving some cells.

This is correct. As a matter of fact, even dosing one chemotherapy may be a challenge for a patient if the side effects are too server (lowered immune resistance, can't keep food down, etc). We're talking about drugs with such small therapeutic windows that given too often can easily kill a healthy human.

Great question. I've wondered the same thing for bacterial infections. Wouldn't it lower the risk of resistant bacteria developing to always use two different types of anti-biotics, so in case a few bacteria develop a resistance to one, they're still killed by the other.

This is much easier for bacterial infections vs cancer -- chemotherapy is (excuse the non-medical phrase) very close to actual poison. Antibiotics are very well-tolerated, so taking two at once is something that could be done and is indeed deployed in serious infections or when there is high risk of one.

This - nearly all antibiotics target parts of the bacterial cell that humans don't have. Antifungals have the problem that many of their targets are shared between eukaryotic fungal cells and our own. Chemotherapy agents have a huge problem in that they are targeting cells that used to be our own. It's a race between toxic to cancer cells and toxic to the rest of you.

For some bacterial infections where resistance is a concern, such as TB, this is already the routine standard. See also anti-HIV medication cocktails.

That isn't the current approach. For instance:

http://www.cancer.org/cancer/breastcancer/detailedguide/brea...

That's general audience information that discusses treatments before and after surgery that are intended to work along with the surgery. If you click through to the various therapies, there is lots of discussion of combining them.

That is very interesting, sorry for spreading misinformation.

Patient 1 did have a recurrence of a single tumor that was resolved with site specific treatment, though her marrow remained clear. I didn't see/hear anything about recurrence in patient 2.

Source: video/source article at http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...

Edit: Accompanying editorial to go along with the paper and video: http://www.mayoclinicproceedings.org/article/S0025-6196(14)0...

Could you explain how this is an example of the free market working well? Clearly this is leading edge medicine but the free market thing escapes me.

If you take a look at the list of new MM therapies hitting the market in just the last 5 years, and the number that are in the pipeline, you can see there has been a surge of investment in MM treatments, when for years the only options were dex and ASCT.

I think all this investment has been bolstered by the market success that Revlimid and Velcade are seeing. These drugs are cheap to produce, sell for about $5k per weekly or biweekly dose, and that a large and growing number of people are very happy to pay for, because they are well tolerated for as long as they work. Revlimid is just a pill you take, Velcade is a shot in the arm, so both are very cheap to administer.

There is huge incentive to keep producing more of these MM treatments, because the MM becomes refractory to each successive therapy over time. If you can make a good first-line treatment which is effective for 3 years on average, that's more than $100k per patient, at what, 90% gross margin?

I don't mean "free market" in the libertarian sense. I mean it in the sense that investment capital follows investment opportunity, and we are definitely seeing that here.

I can't get past the fact that people almost certainly aren't paying for it. Insurance companies must be as very few could afford those costs. As many can't afford insurance, it's more like the free(ish) market. Thanks for your reply, I see what you mean now.

>I think this is one example of the free market working well.

Well Fleming (who discovered antibiotics) was working for the (British) government, so if the above is in any way an indication of "the free market working well", then his extremely more important results were an example of public sponsored research working great.