Governmental Camels and Stem Cell Swag

Is it good business for a drug company to charge – let's say $47,000 for a 10-month cancer treatment – or will such pricing hurt the industry long term?

But forget the business issue. Is it good public policy to allow a company to charge those fees – labelled egregious by some? Especially if the treatment was partially financed with public funds?

Questions such as those stand close to the center of the debate over the intellectual property that will be produced by $3 billion in research funded by California's stem cell agency. Intellectual property policy is the vehicle because that's where CIRM sets its requirements for royalties and revenue-sharing connected to its research. That is also where it sets its requirements for affordable access to stem cell cures that it helps to finance.

The $47,000 treatment cost is not hypothetical. It involves Genentech and its drug, Avastin, which was developed with the help of some clinical trials that were subsidized by the federal government.

On March 15, the Wall Street Journal examined the case of Avastin in a front page story. Reporter Geeta Anand began her piece like this:

"Two years ago, Steven Harr urged Genentech Inc. to lower the price of a key drug that was helping buoy its stock price. He was an unlikely messenger because of his job: a Wall Street research analyst whose investing clients crave profits.

"In a conference room with 30 senior managers from the biotech company, Dr. Harr said he feared patients wouldn't be able to afford the drug Avastin, which costs about $47,000 for the average 10-month course of treatment for colorectal cancer. He warned that Congress 'will get involved when its constituents can't get drugs.' Genentech later capped Avastin's price, acknowledging the influence of Dr. Harr, among many others."

Harr also pointed out an interesting bit of blowback from oncologists detected during a survey he conducted. According to the WSJ story,

"He says most physicians surveyed weren't prescribing the drug in breast and lung cancer for fear of not being reimbursed. Avastin and Erbitux are given to patients intravenously in doctors' offices. Doctors buy the drug ahead of time, infuse it into patients and then wait to be reimbursed. Any refusal by insurers to reimburse would leave doctors thousands of dollars in debt."

Harr, an analyst with Morgan Stanley, sees high prices as bad for business.

"He says soaring cancer-drug prices, generating fat profit margins, aren't sustainable."

That is a message that is sometimes hard for business executives to accept. They rail at governmental fiddling with their enterprises. They froth at bumbling regulators. But at the same time, many seek government assistance for research, favorable regulation, tax benefits or laws restricting their competitors. Contrary to popular belief, the vast majority of legislative activity nationally and in California does not involve such things as gay marriage or sex offenders or drivers licenses. It involves "filthy lucre" and crass commerce. Most of it is instigated by those advocates of free markets – the top executives of the finest companies in America. It is why business spends tens of millions of dollars and more annually lobbying lawmakers.

Folks such as those at the California Healthcare Institute, which represents the state biomedical industry, want the grants from CIRM. But they don't want to pay the piper that provides the basis for the plenititude. Or they don't want to pay as much as some watchdog groups and legislators would like. But like any other investor, the state wants its slice and does not want to be treated a whole lot differently than, say, the venture capitalists at Kleiner Perkins Caufield & Byers, if they had laid out a $3 billion investment. When you invite governmental camels into your tent, it is sometimes hard to get them to leave.

Biotech, however, has valid points concerning writing what are basically the terms of a business deal into state law and regulation. Both are difficult to change and can impair development of cures if they are riddled with restrictive minutia. Likewise, biotech firms must see a strong likelihood of making money. If they don't, the cures will not be developed unless the government is ready to pay for the whole process, which is not likely to happen in our lifetime.

Obviously, the state of California is not a venture capital firm. Perhaps not so obviously, the stem cell industry is not the most shining example of private markets at work. The finest risk-takers in America(venture capitalists) run for the back exits, for the most part, when they see a stem cell executive come through the front door. The result is that with embryonic stem cell research in California, we have an amalgam of business, government and science. That means that compromises must be made by all the players. If one of the partners gets too greedy, the whole endeavor – the California stem cell experiment -- can fail.

Finally we should note that a group actively engaged with CIRM on IP issues was mentioned in the WSJ article but not by name. That organization is the Foundation for Taxpayer and Consumer Rights of Santa Monica, Ca. Here is what the WSJ wrote about FTCR.

"In the spring of last year, a taxpayer group in California began publicly condemning Genentech for charging too much for Avastin, noting that the federal government's National Institutes of Health had subsidized some clinical trials of the drug. Not long after, Genentech said it was considering capping the price of Avastin."

Chiropractors, CIRM and Its Legislative Posture

The 120 men and women who sit in the California Legislature generally tend to think they have prime responsibility for writing the laws that govern the state. And they often get edgy when state agencies, even ones that have special constitutional status, seem to be straying from the governmental straight and narrow.

Such was the case recently with the California's chiropractic board, which is enshrined in the State Constitution. Gov. Arnold Schwarzenegger's appointees to the board became carried away in what a deputy attorney general described as a fit of "lawlessness." Now the board faces a serious legislative investigation that could include elimination of its $3 million budget.

While this is something of a minor tempest – although not for chiropractors -- the chiropractic board shares several things in common with California's much heftier, $3 billion stem cell agency. Both are written into the State Constitution. Both were created by initiative. Both have issues involving conflicts of interest. And both function in near obscurity except when they hand out buckets of money – in the case of the stem cell agency – or when a scandal erupts, as in the case of chiropractic board.

Obviously major differences exist between the two boards, including the quality of the appointees. But the case of the chiropractors illustrates how quickly matters can go awry in an insular agency and how quickly the legislature may move to step in. The case will also probably show how quickly the governor can put distance between himself and what The Sacramento Bee called a "laughingstock."

Last Sunday we discussed the sometimes acrimonious relationship between CIRM and the California legislature, particularly in the light of bipartisan legislation by the chair of the Senate Health Committee, Sen. Sheila Kuehl, D-Santa Monica. Her measure would inject the legislature into the difficult and touchy matter of how the stem cell agency decides to share the potentially enormous wealth from cures developed with state-funded research. After a shaky start with lawmakers, CIRM has moved to improve its legislative relations and keep lawmakers well informed.

Our piece, which appeared as an op-ed in The Sacramento Bee, was necessarily limited because of space. But we wanted to share more that we heard from CIRM and two longtime observers of the agency, who also have been critical of its performance from time to time and sometimes even more often. What follows are virtually verbatim comments.

First, from Dale Carlson, chief communications officer for the stem cell agency:

"We have an active government affairs program underway in Sacramento focused on legislators and statewide office holders, as well as their respective staff members. We want to keep them apprised of our efforts and progress, the status of key regulatory and funding initiatives, and the challenges we are confronting in pursuit of our mandate and obligations.

"The objective is to ensure that key decision-makers have current, accurate, and reliable information about CIRM's activities, the field of stem cell research, and related issues. We seem to receive reports of new scientific developments every week, and with more states committing funding to the field each year, it's likely that pace will accelerate. It's a challenge for us to stay abreast of the science, federal policy, and other states' emerging policies, all of which have an effect on our scientific project.

"We're very proud of the work we're doing, the processes we follow to engage the public in the development of policies and regulations that are required by the law, and the willingness we've demonstrated to adopt and apply good ideas from variety of sources. We want to be recognized as a credible source of information on all things stem cell, regardless of whether the question is directly related to CIRM's activities.

"Our legislative affairs program includes one-on-one meetings and group briefings. (Early in February), for example, ICOC Vice Chair Ed Penhoet and several CIRM staff held a session with staff from the Speaker's office and the Senate Health Committee and others, to review our IP policies for non-profits and for-profits. Both have been the subject of great interest and discussion in Sacramento (as well as throughout the state and in Washington, D.C.), with legislators offering many suggestions for how those policies might be crafted and strengthened. Our presentation described the progress we've made to date - emphasizing that the regulatory process is still moving forward and unlikely to be completed for several months - as well as a review of the issues we're struggling to address. "(Later in February), (CIRM President) Zach Hall, Arlene Chiu, and Mary Maxon (Chiu and Maxon are CIRM staff) conducted a broader briefing on the basics of stem cells, the progress we've made in our first two years, including on the IP policies, and the grants approved by the ICOC.

"Kirk Kleinschmidt, our Director of Legislation and Research Policy, has day-to-day responsibility for the effort. In addition to arranging these group sessions, he's regularly in the capital meeting with individual members. Gene Erbin from Nielsen Merksamer is on retainer to support the effort. Per the provisions of Proposition 71, (Stem Cell Chairman) Bob Klein oversees the legislative affairs program in consultation with the Legislative Subcommittee and the ICOC. He's in regular contact with federal and the statewide office holders as well as the legislative
leadership."

Carlson also said that Klein, Penhoet, Kleinschmidt and Patricia Olson, who led development of the CIRM strategic plan, had a 90-minute meeting with Kuehl last Wednesday.

Carlson said it was a "detailed discussion of our IP policies, the drug/therapy development process and the extensive public process we've followed."

"This is the kind of relationship we want with the legislature. Respectful and substantive. We want them to be assured that we're going about our responsiblities thoughtfully and carefully, and that we welcome good ideas and the opportunity to discuss our efforts."

Carlson said the CIRM board will meet in Sacramento April 10 and expects to finish its meeting in time for board members to visit with legislators in the afternoon.

Jesse Reynolds, project director on biotechnology accountability for the Center for Genetics and Society in Oakland, has followed CIRM closely during the last two years as well as the Prop. 71 campaign.

Here is what he had to say in response to our query:

"Prop. 71 is a deeply flawed set of laws, with numerous exemptions to the norms of transparency, oversight and accountability....

"Hopefully, the leadership of the CIRM won't be as hostile to much-needed reform as it was during previous attempts. Then, the state's 'stem cell czar,' Robert Klein took the unprecedented step of hiring a lobbyist with taxpayer funds. What's more, while serving as chair of the CIRM's governing board, he simultaneously headed up a private lobbying organization, which advocates for more funding and less oversight of stem cell research. These actions are not appropriate for the head of a state agency.

"Klein's statements that 'the Legislature is not needed' and that then-Senator Ortiz was 'an ongoing threat' are not only wrong, but highlight his cavalier attitude in his role as a public servant. As the people's elected representatives, the Legislature certainly has a critical role in overseeing a multi-billion dollar program. As a senator, Ortiz did more for stem cell research and Proposition 71 than any other elected official."

John M. Simpson, stem cell project director for the Foundation for Taxpayer and Consumers Rights in Santa Monica, Ca., is another longtime follower of CIRM matters. He said,

"Key to any IP policy are provisions that ensure affordable access for all Californians to any cures or treatments resulting from stem cell research they funded. The ICOC originally envisioned meeting that goal by requiring treatments purchased with public funds to be sold at the federal Medicaid price and that there be a plan in place that would provide access to the treatments for uninsured people.

"In drawing up the actual regulatory language to implement those policies, the ICOC has softened those proposals.....

"I think Kuehl's bill would increase payback to the state, but doesn't do enough to ensure affordable access for all Californians. There should be a provision that if there are unreasonable prices the attorney general can intervene. I cite Genentech's Avastin as an example of what cannot be allowed. The drug was developed with $44.6 million in public funds from the National Cancer Institute yet Genentech charges $100,000 a year for it.

"I'd also like to see action on governance and accountability issues. I don't know what Sen. Kuehl's plans are in this regard. Members of the various working groups should be required to file public disclosures of their interests. All applicants and their institutions should be identified, not just recipients. Finally the ICOC is too large. It should be trimmed from the 29 members who now have seats.

"Another thought: ICOC members themselves have expressed concerns about some provisions of Prop 71. It might be useful for both CIRM and the legislature to attempt to identify such areas and agree on making those changes."

CIRM IP Legislation Faces Tall Hurdle

The following – written by yours truly -- appeared today in The Sacramento Bee as an op-ed piece. We will bring you more details of CIRM's current legislative efforts on Monday.

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Nearly three years ago, California voters created a unique and nearly autonomous agency that set the state on a $3 billion foray into embryonic stem cell research. Under the terms of Proposition 71, voters told the new California Institute for Regenerative Medicine to hand out $300 million annually in hopes that the grants would lead to cures for everything from diabetes to cancer.

Voters also told legislators not to mess with the institute at least for three years. Now that time is nearly up. And two powerful legislators are mounting the first effort -- under the terms of Proposition 71 -- to intervene in the institute's affairs.

The stakes are enormous and involve potentially billions of dollars of profits from stem cell therapies and cures.

The legislation was introduced last month by the chair of the Senate Health Committee, Sheila Kuehl, D-Santa Monica, and the Republican caucus leader in the Senate, George Runner of Antelope Valley. Their Senate Bill 771 is aimed at ensuring that California receives a healthy return on its investment and that state-funded cures are affordable and accessible.

But the senators face an extraordinary obstacle. Under Proposition 71, their legislation requires not just a majority vote to pass -- not just a supermajority vote (two-thirds) -- but a super, supermajority vote of 70 percent. That means 13 senators can kill the bill.

California's biotech industry and the institute are probably already compiling a list of their 13 best friends in the Senate. The state's leading biomedical organization, the California Healthcare Institute, is unhappy with the stem cell institute's intellectual property rules for sharing the wealth, declaring that they provide "a substantial disincentive" for creating commercial cures.

The rules determine who owns the results of the state-funded research, in other words, the intellectual property. They also determine how the intellectual property may be used and who, including the state, will receive royalties and under what conditions.

The California Healthcare Institute has not taken a position on Kuehl's bill but has indicated that it does not want to be hamstrung.

Runner and Kuehl, however, have an unlikely source of support. That's the legacy of the less-than-adroit legislative maneuvers by California stem cell Chairman Robert Klein. Much as President Bush's decision to limit funding for stem cell research spawned Proposition 71, Klein's actions ironically have fostered an environment conducive to the Kuehl bill's success.

Klein not only irritated some lawmakers, but some members of the stem cell institute's Oversight Committee as well. They were not pleased by his broadsides, such as denouncing the former chair of the Senate Health Committee, Deborah Ortiz, D-Sacramento, as an "ongoing threat." That message was delivered last year in a widely disseminated e-mail to patient groups via Klein's nonprofit advocacy group, Americans for Stem Cell Therapies and Cures.

The stem cell institute has attempted to strengthen its legislative ties. It took the unusual step, for a state agency, of hiring a private lobbyist, the well-connected Nielsen, Merksamer, Parrinello, Mueller & Naylor for $4,100 a month. More recently, the institute reached out to lawmakers and legislative staff, sending delegations to Sacramento twice last month, including Zach Hall, the institute's president, and Ed Penhoet, vice chair of the Oversight Committee and head of its intellectual property task force.

Kuehl has a tall hurdle to clear -- the 70 percent vote, not to mention the governor. She is stepping into a complex arena -- intellectual property -- where little unanimity exists, as the institute has discovered. But even if the bill fails, it will help to provide broader input on policies about intellectual property, developed during sparsely attended hearings. The measure additionally will serve as an important test of the institute's openness and political savvy.

While the agency is uniquely independent, California lawmakers are capable of creating much mischief when they feel their constituencies have been slighted. And that is mischief that the institute should avoid, so it can focus on its primary mission, as the institute proclaims, "turning stem cells into cures."

State Audit: CIRM Likely to Find the Devil in the Details

Dispassionate blandness dominated the report by the California State Auditor on the state's $3 billion stem cell agency, but the details are certain to provide ammunition for the full range of its critics.

The auditors picked apart the two-year-old agency and many of its procedures. Its overall findings seemed reasonable enough that CIRM itself pronounced the report "accurate," "fair" and "valuable." Certainly many of the auditor's findings were to be expected involving the fledgling agency that, in many ways, initially was more like a semi-floundering business startup than a government department.

But the details from the report are likely to be aired with vigor during upcoming public hearings on the billion dollar issues involving who shares the wealth – if any – from state-funded stem cell discoveries – not to mention affordable access to stem cell cures and therapies.

The auditor also raised to a new level long-standing questions – including those by this blog -- about conflicts of interests involving the persons who review tens of millions of dollars in CIRM grant applications.

The auditor recommended that CIRM seek an opinion from the attorney general on its position that grant reviewers do not need to make a public disclosure on their economic interests. The auditor said:

"In view of the seriousness of a violation of conflict-of-interest laws and the concerns raised by the FPPC, we believe that it would benefit the institute to seek a formal opinion from the attorney general regarding whether the exemptions created for working groups from conflict-of-interest laws are intended to exempt them from the conflict-of-interest provisions that apply if the recommendations of an advisory body are adopted routinely and regularly by the decision-making body to whom they are made."

The auditor referred to previously undisclosed exchanges between the Fair Political Practices Commission, which is charged with overseeing the state's economic disclosure laws, and CIRM. The FPPC, the auditor said, believes working group members "may act as decision makers if they make substantive recommendations that are, over an extended period, regularly approved without significant amendment or modification by the (CIRM Oversight) committee." That means that reviewers would have to make a public disclosure of their economic interests.

CIRM says it is consulting with its private attorneys to determine whether to seek an opinion from Attorney General Jerry Brown. (We will have more on this subject in a separate item later today.)

Some of the other details likely to be bandied about publicly involve already-being-corrected contracting procedures that seemed a little fast and loose – our words, not the auditors – along with chauffeured vehicles, lunches that cost $36, dinners that cost $65 and pricey air travel.

But the big money issues – perhaps running into billions of dollars - surround formulation of CIRM's intellectual property rules -- sharing the profits from stem cell therapies and cures, as well providing affordable access to those therapies and cures.

The subject is known as IP. CIRM has spent many months wrestling with the issue, trying to come up with solid, well-supported policies. Its IP meetings have been sparsely attended even by institutions and businesses that would be deeply affected by CIRM's decisions. The public has been invisible along with the media, for the most part. Often times because of its unique nature, CIRM ventured into an IP wilderness where no trail guides existed.

Auditors complained of the lack of documentation for CIRM's existing policies. For example, the report said, "The vice chair and his deputy could not provide adequate documentation to demonstrate why the 25 percent (royalty) figure is an appropriate payment from nonprofit organizations. As such, they also could not demonstrate that 17 percent is an appropriate payment from for-profit grantees."

At another point, the auditor remarked on the fraility of notes in scores of interviews conducted by CIRM staff involving IP, saying, "Most of the information in the notes consisted of stand-alone sentences and references with very little or no context."

And there was more. This is what auditors do. They pick apart material that was often gathered not knowing that it would be subject to such exquisite scrutiny. Newspaper reporters sometimes find themselves in a similar situation involving their notes and stories when litigation comes up, as the news gatherers testifying in the Libby trial in Washington, D.C., recently learned.

Nonetheless, it will all be fodder as hearings begin later this year on IP legislation (SB771)by Sen. Sheila Kuehl, D-Santa Monica, chair of the Senate Health Committee. Her position is that CIRM has not done enough to ensure a return to the state and to provide affordable access. The auditor's report will fit neatly into her arguments.

From CIRM's perspective, the auditor's report could have been worse, and it could have been better. CIRM's formal response embodied in the report was tactful and appropriate. The audit offers a road map to improvements, many of which CIRM already knew needed to be made. But an outside voice can provide the sharp prod to ensure that they are accomplished.

Legislature Posts Text of CIRM Legislation -- SB771

The text of legislation aimed at ensuring a return to the state on cures developed as a result of research funded by the California stem cell agency was posted officially today on the Internet.

The measure did not contain any surprises. However, it did contain a necessary provision that has not been mentioned previously. That language declared that the proposal would enhance CIRM's ability to carry out the purposes of Prop. 71. The initiative stipulates that legislative changes in the act must enhance its purposes. That is on top of the unprecedented requirement for a super, supermajority vote (70 percent) to approve such bills.

The "enhancement" requirement was presumably inserted into Prop. 71 to provide another weapon to battle legislative changes under terms authorized by the initiative. Since this is the first such attempt, its effectiveness as an opposition tool is yet to be tested. Previous legislation concerning CIRM used different legal approaches.

The number of the bill, SB771, was also picked to resonate with Prop. 71, according to the office of Sen. Sheila Kuehl, D-Santa Monica, chair of the Health Committee, who authored the proposal along with Sen. George Runner of Antelope Valley, the leader of Senate Republicans.

Here are the key elements of the bill, which is not likely to be heard in committee for some time:

"The standards that the ICOC develops shall do all the
following:

"(A) Require every recipient of a grant or loan award for research
to provide to the state 25 percent of the net licensing revenues it
receives associated with any institute-funded patented invention
beyond a reasonable revenue threshold that the ICOC may establish.
Net licensing revenue shall include all forms of financial
consideration from licensing and shall be defined as gross licensing
revenues, less patent expenses and reasonable payments to inventors.

"(B) Require every recipient of a grant or loan award for research
to grant exclusive licenses involving institute-funded patented
inventions relevant to development of therapies, drugs, and
diagnostics only to organizations that have plans which the institute
determines will provide substantial access to the resultant
therapies, drugs, and diagnostics to uninsured Californians. In
addition, the licensees shall agree to provide to patients whose
therapies, drugs, and diagnostics will be purchased in California
with public funds, the therapies, drugs, and diagnostics at the
federal Medicaid price.

"(C) Require any recipient of a grant or loan award for research
that commercializes any product that it develops using institute
funds to agree, as a condition of accepting the funds, to make
royalty payments to the state equal to 2 to 5 percent of the revenues
over the life of the product, depending on the level of funds
provided and contribution of institute-funded patented inventions to
the development of the product."

CIRM IP Legislation Begins Its Journey to Mixed Reviews

The chair of the California State Senate Health Committee today formally unveiled her legislation aimed ensuring the state receives a return on its $3 billion investment in stem cell research. But the measure initially met with mixed reviews.

One potential ally wanted more and foes want less. CIRM itself said no comment would be forthcoming until it had seen the official text of the legislation (SB771), which is not available at the time of this writing.

The bipartisan bill, as presented in the press release by Sen. Sheila Kuehl, D-Santa Monica, seemed to measure up to earlier information (see "CIRM Regulation").

John M. Simpson, stem cell project director for the Santa Monica-based Foundation for Taxpayer and Consumer Rights, said,

"The bill does not go far enough to ensure that all Californians have affordable access to the cures and treatments that result from stem cell research they are funding.

"There needs to be a provision that allows the attorney general to intervene if these therapies, treatments or cures are priced unreasonably.

"It's good that the bill would require an an access plan for uninsured people and that it would require purchases funded with public funds be made at the Medicaid price. The problem is that it doesn't do enough for all Californians who are paying to develop these treatments with their hard-earned tax dollars."

Jesse Reynolds, project director on biotechnology accountability for the Oakland-based Center for Genetics and Society, welcomed the measure, declaring,

"If a biotech company is making billions of dollars of profit from state-financed research, the people should receive a fair return on their investment, as well as access to any therapies."

Reynolds said the leadership of the stem cell agency has tried to "back out" of Prop. 71 campaign promises of huge economic returns to the state. He said,

"This would have been a billion-dollar bait and switch. The bill will make significant steps toward fulfilling these promises."

The California Healthcare Institute, which represents the state's biomedical industry, did not have an immediate comment. But the group is already opposed to CIRM intellectual property policies, which Kuehl says are too weak.

CHI says on its stem cell research page that CIRM's IP rules

"threaten to discourage commercial collaboration, technology transfer and licensing by (a) increasing the administrative complexity of licensing agreements involving CIRM-funded technologies in comparison to the mainstream of academic-industry transactions, which derive from federally-funded research, and (b) increasing investors' financial risk by imposing state price regulation on downstream products."

We should note that not all companies involved in development of the CIRM IP rules share CHI's adamant opposition to CIRM's IP rules. (CHI's stem cell page contains several links to more of its documents filed concerning CIRM IP.)

Kuehl drummed up some media attention in advance, granting interviews to both the San Jose Mercury News (see "CIRM Regulation") and Terri Somers of the San Diego Union-Tribune. Somers quoted Kuehl as saying,

“Californians are putting billions of dollars into this research. They ought to be guaranteed to get a little bit back, because everyone else is going to be on the take."

For more on the legislation, including the difficult task Kuehl faces, see "Rationale Behind" and "Legislators Target."