VentureBeat

(UPDATED: See below.)

Erythropoietin, or EPO, and its close relatives didn’t become the world’s most popular biotech drugs — at least through last year, when they pulled in sales of almost $12 billion — for nothing. On the plus side of the ledger, the anemia treatment owed its early success to the near miraculous improvement it wrought in the health of kidney-dialysis patients, who previously required numerous blood transfusions and frequently died relatively quickly anyway. On the other side, though, EPO makers, primarily Amgen and Johnson & Johnson, have long pushed hard to boost dosage and use of the drugs in a variety of situations, even when the evidence of patient benefit was weak and sometimes in the face of worrisome early signs that the drugs might actually be hurting instead of helping. (See our previous coverage here and here.)

In light of evidence this year that high doses of EPO increase the risk of blood clots, heart attacks and death, and that the drug might also encourage tumor growth, it was encouraging to see J&J announce yesterday — to the WSJ, at least — that it’s dropping efforts to expand EPO use in surgical and trauma patients. The main reason: Negative findings in a large J&J-funded study published yesterday in the New England Journal of Medicine, which reported that use of J&J’s EPO, brand-named Procrit, failed to reduce the number of transfusions or even the quantity of transfused red-blood cells among patients in intensive care.

That trial did produce equivocal evidence that EPO might contribute to the survival of these critically ill or injured patients, as there were fewer deaths among those who received Procrit at both day 29 and day 140 following their first injection. The result at day 140, however, wasn’t statistically significant. More worrisome was the fact that EPO use was associated with a 45 percent rise in blood-clot related events, including lung clots, deep-vein clots and heart attacks. Not that long ago, J&J would have most likely pointed to the mortality data as evidence of benefit and planned another study. Not this time, particularly when the same issue of the NEJM also carried an editorial warning against routine use of EPO in the ICU.

On the other hand, the EPO lobby isn’t close to folding its tent. Over at GoozNews, Merrill Goozner recently noted a sly provision slipped into a children’s health-insurance bill that would likely boost EPO use in dialysis patients, quite possibly to dangerous levels — and at a cost to taxpayers of $100 million a year. The details are too complex to get into here, but Merrill does a great job of laying it all out, so head over and take a look, and marvel at the tenacity of drugmakers who are down but nowhere near out.

UPDATE: The In Vivo blog offers this weighty analysis — and I mean that in a good way — of what to expect as yet another FDA committee looks into EPO usage and side effects next week.

Is the bell tolling for EPO? – The news keeps going from bad to worse for the wonder drugs of biotech — the anemia treatments known as ESAs or EPO, shorthand for “erythropoiesis stimulating agents” and “erythropoietin,” respectively. Earlier today, an FDA advisory panel recommended new warnings for the drugs, which stimulate the production of oxygen-carrying red blood cells, as well as fresh clinical studies on their safety. Recent studies in kidney-dialysis patients linked higher doses of ESAs to heart problems and strokes, while studies in cancer patients treated for chemotherapy-related anemia have suggested that the treatments don’t improve patient survival, and may even cut lives short — possibly by encouraging tumor growth.

New restrictions, which the panel didn’t spell out, could put a serious crimp in ESA sales, which currently amount to billions of dollars for Amgen and Johnson & Johnson. The two companies have also been taking a public-relations battering in terms of how they promote the drugs. Yesterday, the NYT ran a front-page piece that detailed how rebates offered by Amgen and J&J encourage doctors to overuse the drugs, and today the WSJ followed with a look at whistleblower allegations that J&J boosted EPO sales by pushing higher-than-approved doses.

It’s worth remembering that while the storm is currently walloping industry giants like Amgen and J&J, plenty of smaller biotechs that have staked their hopes on getting into the anemia-treatment game could eventually be affected as well. These companies include Affymax, FibroGen and Neose. Only Affymax is public; another potential ESA competitor, GlycoFi, was acquired by Merck last year.

First embryonic stem-cell trial edges forward – By early next year, Geron plans to be injecting recent spinal-injury patients with nerve cells grown from embryonic stem cells, in hopes of regenerating damaged nerve pathways. This trial was supposed to be underway already, but last year the FDA requested more animal data for safety purposes. Geron CEO Thomas Okarma says the treatment will have been tested in 2,000 animals before it ever reaches humans. The FT’s Clive Cookson has the story.

Aggressive treatment leads to worse “quality of death” in cancer patients – File this one under things you already knew but didn’t want to think about. A study of 243 advanced cancer patients revealed that a greater number of aggressive treatments — including the use of ventilators and non-palliative chemotherapy — in the last week of life was associated with greater physical and psychological distress and a lower chance of dying in a preferred location (often home). Money quotes:

[Said study lead author Gabriel Silverman:] “These results suggest that when patients are actively dying, the use of aggressive treatments should be considered with caution and only pursued with the full understanding of patients or their surrogate decision makers.

[...]

“As a doctor, if I had a patient or family who wanted aggressive, life-sustaining care toward the end of their life, I would view it as a red flag warning of patient or caregiver distress,” Dr. [Robert] Arnold [of the University of Pittsburgh] concluded. “Often patients and their families are suffering, sad, or distressed at the end of life, and when dying occurs in medical settings they may hope that aggressive treatment will help the suffering, but often it doesn’t.”

Tau gets a little respect – For the past decade or so, Alzheimer’s researchers have concentrated their attention on beta amyloid, the protein that clumps around neurons in “tangles” visible in the autopsied brains of many — though not all — Alzheimer’s patients. Now comes evidence that a dark-horse protein called tau may also bear some responsibility for the disease. Researchers reported last week in Science that they reversed memory loss in mice by tinkering with their genes to produce lower levels of the tau protein. It’s heartening to see competing theories getting some attention in the Alzheimer’s community, which has had an unfortunate tendency to shun researchers who strayed from the majority opinion, but don’t expect beta-amyloid supporters to give much ground until they have to. That might be soon, as a new batch of drugs designed to block formation of beta-amyloid tangles should begin reporting data from human trials later this year.

New genetic heart-disease link – Another whole-genome association study has identified a new genetic variation that appears to increase heart-attack risk by 60 percent in European populations. The catch is that the variation doesn’t appear to be associated with any known gene, and instead exists in the long stretches of non-coding, or “junk,” DNA, meaning that no one has any idea why it should have any effect on heart-attack rates. The NYT has more.

Stem-cell researchers make like Willie Sutton – Near the end of this otherwise unremarkable account of a talk by James Thomson, the Wisconsin researcher who first isolated and grew human embryonic stem cells, comes this interesting nugget: Thomson will open a “satellite laboratory” on the UC Santa Barbara campus for stem-cell collaborations with UCSB researchers. Coincidentally enough, having a presence in the state might also qualify Thomson for funding by California’s $3 billion stem-cell program. Willie Sutton, you’ll recall, is the outlaw who once proclaimed that he robbed banks “because that’s where the money is.” Some sentiments, it seems, are universal.

Hypocrisy in the generic-biologics fight? – The prospect of legislation that clears a path for “generic” versions of expensive biotech drugs appears to have dimmed significantly. But biotech consultant and blogger David Williams — no fan himself of the push for “biogenerics” — notes that biotech companies and their lobbyists may be shooting themselves in the foot when they argue that biogenerics could never be “identical” to branded products now on the market. It’s worth reading his entire post — it’s not long — but the gist is that changing the manufacturing process for name-brand biotech drugs, which happens all the time, opens up the same “equivalence” issues that BIO and its allies find insurmountable where biogenerics are concerned. The main difference is that name-brand manufacturers can handle the issue with short, inexpensive “bioequivalence” trials — but they insist that biogenerics must undergo expensive, full-blown clinical testing to assure their efficacy and safety. If the biogenerics issue heats up again, don’t be surprised to see this argument make a comeback.

Surgical robots in space, stem cells in rodent eyes – These are just two interesting stories from the San Jose Mercury News I haven’t yet had a chance to mention. Last Sunday, the Merc ran this piece on efforts to automate surgery, with the ultimate goal of building robots that could operate on astronauts in space or soldiers on the battlefield. Far off and far out stuff. Similarly, this piece outlined the possibility of growing new blood vessels using an early and highly regenerative stem cell called a hemangioblast. Ultimately, these fast-growing cells could one day regrow blood vessels in the heart, eyes or limbs that were damaged by injury or disease.

Amgen’s anemia rollercoaster — Biotechnology titan Amgen may have dodged a bullet when a study released Thursday showed that its anemia drug Aranesp didn’t shorten the lives of patients, after several other studies had suggested the opposite. But its anemia franchise isn’t out of the woods yet. A Wednesday report in the Journal of the American Medical Association revealed that for-profit dialysis clinics prescribe far higher doses of anemia drugs to their patients than do their non-profit counterparts, suggesting a profit motive behind the overuse of drugs that have been linked to cardiovascular problems at high doses.

Now it appears that Congress may weigh in: The WSJ quotes Rep. Fortney “Pete” Stark, a California Democrat, calling for changes in Medicare reimbursement to eliminate any incentive to overuse the drugs, which stimulate production of the red blood cells that carry oxygen.

More on “generic” biologics — Here are two takes on the move to allow copycat versions of biotech drugs that I neglected to mention in yesterday’s post on the subject. Writing at Forbes.com, Scott Gottlieb — former FDA deputy commissioner for medical and scientific affairs, now a pundit at the neoconservative American Enterprise Institute — makes the counterintuitive argument that copycat biotech drugs will speed the development of new drugs, even if they’re just simply improved versions of older ones.

Meanwhile, pharma/biotech consultant David E. Williams dismisses the biogenerics push as “a bad bill that deserves to die” on his Health Business Blog, but suggests that Congress could adopt a more straightforward solution: Simply mandate price cuts on biotech drugs once their patents expire. It’s such a wacky but weirdly intriguing idea that I can’t even tell if it makes sense, but I certainly doubt that Congress could muster the political will for such a naked exercise of government power — it simply violates too many current assumptions about the usefulness and necessity of markets.

Stem cell divisions — The president of California’s $3 billion stem-cell research program resigned abruptly on Tuesday, citing both health concerns (a recent diagnosis of prostate cancer) and tensions between patient advocates and biomedical academics over plans to spend up to $300 million on new research facilities. Zach Hall’s departure will now come earlier than expected — he’ll depart at the end of April instead of the end of June — but plans to name a successor are already underway. Despite his title, Hall wasn’t the head honcho of the California institute; that honor is reserved for Robert Klein II, chairman of the inaptly named Independent Citizens Oversight Committee, who is also rumored to have clashed with Hall more than once. David Jensen of the estimable California Stem Cell Report has all the details.

Dollars for doctors (and everyone else) — Why does U.S. healthcare cost so much? The economics blog Marginal Revolution hosted a fascinating debate on the subject earlier this week, prompted by Tyler Cowen’s capsule review of a new book by Maggie Mahar titled Money Driven Medicine. The argument is too complex to do it much justice here; the best summary I can make without writing an essay myself is that the entrepreneurial instincts of doctors and medical-technology suppliers (including drug companies), combined with weak resistance from desperate patients, leads to market failure, including drastic overuse — and misuse — of medical services. Don’t miss Mahar’s contribution to the Marginal Revolution debate in comments. Two other takes on the book are here and here.

In a similar vein, this post from the group blog Health Care Renewal aims to explain why so many academic researchers seek out funding from pharmaceutical and biotech companies these days. Turns out it’s not just the greed of companies eager to co-opt paragons of the ivory tower; instead, blogger Roy Poses suggests that university incentives similar to the ones that motivate car salesmen are at fault. Definitely worth a read if the question has ever crossed your mind.

Research odds and ends from the week that was:
• Scientists discovered a gene that appears to be key to “self-renewal” in both embryonic and adult stem cells.

• Surgeons are exploring ways of conducting minimally invasive procedures using “natural openings” in the body such as the mouth, the rectum or the vagina.

• Take that, white supremacists: Physical anthropologists now believe that European skin only lightened up 6,000 to 12,000 years ago, suggesting that “our European ancestors were brown-skinned for tens of thousands of years” prior to that. The link is subscription-only, so here’s a brief snippet of the Science news article:

Researchers have disagreed for decades about an issue that is only skin-deep: How quickly did the first modern humans who swept into Europe acquire pale skin? Now a new report on the evolution of a gene for skin color suggests that Europeans lightened up quite recently, perhaps only 6000 to 12,000 years ago. This contradicts a long-standing hypothesis that modern humans in Europe grew paler about 40,000 years ago, as soon as they migrated into northern latitudes. Under darker skies, pale skin absorbs more sunlight than dark skin, allowing ultraviolet rays to produce more vitamin D for bone growth and calcium absorption. “The [evolution of] light skin occurred long after the arrival of modern humans in Europe,” molecular anthropologist Heather Norton of the University of Arizona, Tucson, said in her talk.

(Note: This item has been copied over to the Life Sciences page from its original location on the VentureBeat main page. To view it in its original context, with comments, click here.)

Amgen’s anemia rollercoaster — Biotechnology titan Amgen may have dodged a bullet when a study released Thursday showed that its anemia drug Aranesp didn’t shorten the lives of patients, after several other studies had suggested the opposite. But its anemia franchise isn’t out of the woods yet. A Wednesday report in the Journal of the American Medical Association revealed that for-profit dialysis clinics prescribe far higher doses of anemia drugs to their patients than do their non-profit counterparts, suggesting a profit motive behind the overuse of drugs that have been linked to cardiovascular problems at high doses.

Now it appears that Congress may weigh in: The WSJ quotes Rep. Fortney “Pete” Stark, a California Democrat, calling for changes in Medicare reimbursement to eliminate any incentive to overuse the drugs, which stimulate production of the red blood cells that carry oxygen.

More on “generic” biologics — Here are two takes on the move to allow copycat versions of biotech drugs that I neglected to mention in yesterday’s post on the subject. Writing at Forbes.com, Scott Gottlieb — former FDA deputy commissioner for medical and scientific affairs, now a pundit at the neoconservative American Enterprise Institute — makes the counterintuitive argument that copycat biotech drugs will speed the development of new drugs, even if they’re just simply improved versions of older ones.

Meanwhile, pharma/biotech consultant David E. Williams dismisses the biogenerics push as “a bad bill that deserves to die” on his Health Business Blog, but suggests that Congress could adopt a more straightforward solution: Simply mandate price cuts on biotech drugs once their patents expire. It’s such a wacky but weirdly intriguing idea that I can’t even tell if it makes sense, but I certainly doubt that Congress could muster the political will for such a naked exercise of government power — it simply violates too many current assumptions about the usefulness and necessity of markets.

Stem cell divisions — The president of California’s $3 billion stem-cell research program resigned abruptly on Tuesday, citing both health concerns (a recent diagnosis of prostate cancer) and tensions between patient advocates and biomedical academics over plans to spend up to $300 million on new research facilities. Zach Hall’s departure will now come earlier than expected — he’ll depart at the end of April instead of the end of June — but plans to name a successor are already underway. Despite his title, Hall wasn’t the head honcho of the California institute; that honor is reserved for Robert Klein II, chairman of the inaptly named Independent Citizens Oversight Committee, who is also rumored to have clashed with Hall more than once. David Jensen of the estimable California Stem Cell Report has all the details.

Dollars for doctors (and everyone else) — Why does U.S. healthcare cost so much? The economics blog Marginal Revolution hosted a fascinating debate on the subject earlier this week, prompted by Tyler Cowen’s capsule review of a new book by Maggie Mahar titled Money Driven Medicine. The argument is too complex to do it much justice here; the best summary I can make without writing an essay myself is that the entrepreneurial instincts of doctors and medical-technology suppliers (including drug companies), combined with weak resistance from desperate patients, leads to market failure, including drastic overuse — and misuse — of medical services. Don’t miss Mahar’s contribution to the Marginal Revolution debate in comments. Two other takes on the book are here and here.

In a similar vein, this post from the group blog Health Care Renewal aims to explain why so many academic researchers seek out funding from pharmaceutical and biotech companies these days. Turns out it’s not just the greed of companies eager to co-opt paragons of the ivory tower; instead, blogger Roy Poses suggests that university incentives similar to the ones that motivate car salesmen are at fault. Definitely worth a read if the question has ever crossed your mind.

Research odds and ends from the week that was:
• Scientists discovered a gene that appears to be key to “self-renewal” in both embryonic and adult stem cells.

• Surgeons are exploring ways of conducting minimally invasive procedures using “natural openings” in the body such as the mouth, the rectum or the vagina.

• Take that, white supremacists: Physical anthropologists now believe that European skin only lightened up 6,000 to 12,000 years ago, suggesting that “our European ancestors were brown-skinned for tens of thousands of years” prior to that. The link is subscription-only, so here’s a brief snippet of the Science news article:

Researchers have disagreed for decades about an issue that is only skin-deep: How quickly did the first modern humans who swept into Europe acquire pale skin? Now a new report on the evolution of a gene for skin color suggests that Europeans lightened up quite recently, perhaps only 6000 to 12,000 years ago. This contradicts a long-standing hypothesis that modern humans in Europe grew paler about 40,000 years ago, as soon as they migrated into northern latitudes. Under darker skies, pale skin absorbs more sunlight than dark skin, allowing ultraviolet rays to produce more vitamin D for bone growth and calcium absorption. “The [evolution of] light skin occurred long after the arrival of modern humans in Europe,” molecular anthropologist Heather Norton of the University of Arizona, Tucson, said in her talk.