It’s no surprise, then, that the prospect of a new treatment for people with medically refractory epilepsy would be greeted with great enthusiasm. As an adjunct to AEDs, the responsive neurostimulator system, or RNS, under development by Mountain View, Calif.-based NeuroPace, is designed to detect abnormal electrical brain activity and deliver electrical stimulation to regulate brain activity before a seizure develops. The RNS could become the first electrical stimulation device approved by the FDA in epilepsy since vagus nerve stimulation was green-lighted in 1997.

But the results of the Feb. 22 FDA adcom meeting evaluating the NeuroPace RNS raise troubling questions about regulatory decisions in epilepsy care. As reported in Medical Device Daily, the FDA briefing documents submitted for the Neurological Devices Panel of the Medical Devices Advisory Committee meeting indicated that a pre-specified statistical analysis plan of NeuroPace’s prospective, randomized, double-blind, sham-stimulation-controlled pivotal study called for the use of a generalized estimating equation (GEE) model and required that superiority be demonstrated based on a reduction in the frequency of total disabling seizures during the blinded evaluation periods (BEP).

However, neither the study protocol nor the statistical analysis plan “explicitly stated” which of two methods would be used to estimate standard error, producing what the FDA called “distinctly different p-values” for the primary efficacy endpoint. The agency and sponsor concurred that an alternative model was needed, agreeing to use the Poisson regression model. Although the FDA recommended that monthly seizure counts be used, NeuroPace chose the daily model, with the expectation that many seizure-free days would occur in the treatment group and there would not be a clinically meaningful way to group data.

That premise seemed reasonable, since seizure activity can vary from day to day. However, the observed variability in the study exceeded the expected variability in daily seizure counts following a Poisson distribution. NeuroPace then made ad hoc modifications, reverting to monthly seizure counts along with the use of a negative binomial distribution to analyze the returns. According to the FDA, NeuroPace had to add an adjustment for clinical co-variates along with the other modifications to achieve statistical significance for the primary efficacy endpoint.

With these modifications, the pivotal study showed a statistically significant 37.9 percent reduction in seizure frequency in the treatment group compared to a 17.3 percent reduction in the control group during the three-month BEP. Long-term results showed median seizure frequency reductions of 44 percent and 53 percent, respectively, at one and two years post-implant.

Statistical Qualms Bubble Up

In its briefing docs, the FDA argued that some alternative post-hoc GEE models did not achieve statistical significance, none of the pre-specified secondary endpoints achieved statistical significance and no observed data analyses achieved statistical significance. Moreover, response to the device varied by the number of seizures seen at baseline, and findings from the treatment arm may have benefited from two patients on the sham arm with a different response pattern than others in the trial.

Despite these statistical qualms, 12 of 13 adcom members agreed there was “reasonable assurance” that the NeuroPace RNS system is effective for patients meeting the criteria for the proposed indication: adults with partial onset seizures from no more than two foci who are refractory to two or more AEDs. One panelist – a statistician – abstained. The panel voted unanimously that the system is safe, and 11 members concurred that the RNS benefits outweighed the risks, with two abstentions.

I understand the genuine desire to offer hope to epilepsy patients with uncontrolled seizures. My husband developed epilepsy at age 15 a year after a serious head injury, and he is not seizure-free after 40 years on various combinations of AEDs and a left temporal lobectomy.

But should the FDA permit statistical manipulation in epilepsy that would likely raise eyebrows in other indications? At BioWorld Today, I write about the development of drug therapies designed to treat individuals with cancer, hemophilia, multiple sclerosis, Alzheimer’s disease and many other poorly treated diseases. I understand the desire to bring new treatment options to patients with agonizing conditions. I really do.

I also see countless drugs rejected by the FDA when efficacy is not assured, even when safety is unquestioned. And, compared to medical management, the implantation of a deep brain stimulator is not inherently safe. Up to one in five patients could be expected to have a serious adverse event related to implantation and related medical procedures, according to the FDA’s own risk/benefit analysis of the RNS. Shouldn’t the burden of proof for such a device be even higher than that of a drug?

Above All, Demonstrate Efficacy

With respect to epilepsy, quality of life implications often are cited as a compelling reason for drug or device approval, with patients seemingly willing to accept a higher risk threshold in return for the prospect of improved seizure control. In my view, that premise should be predicated on demonstrated efficacy. In the real world, physicians are quick to suggest new treatments, and patients often are desperate. Few have the benefit of advocates with neurological expertise who can provide an unvarnished appraisal of a newly approved therapy. I wake up every morning with someone who has run the epilepsy treadmill, trying therapies touted for their efficacy that proved futile, and worse.

The NeuroPace RNS may, indeed, help some epilepsy patients, which would be a terrific outcome for the developer and the epilepsy community, alike. However, that claim seems far from proven, which should give the FDA pause in approving its usage without additional study. Individuals with epilepsy deserve treatments that offer true hope, not outcomes derived on the basis of statistical tinkering.

Editor’s note: To read more about Marie and Chuck Powers’ experiences with epilepsy and an unusual condition that surfaced after a temporal lobectomy ‑ prosopagnosia ‑ visit her personal blog, About Face.

“1. Dr. Wanda Jones, who I trust and respect, in the Assistant Secretary of Health’s office has engaged with the Secretary of Health over the past days on the need for a serious commitment to address our unmet needs.
2. Dr. Jones committed to me that the Secretary’s office will be engaged in the FDA Stakeholder Meeting this Spring to make it a successful meeting in promoting the need and path forward toward evidence-based treatments.
3. For the first time, Secretary Kathleen Sebelius met with a few ME/CFS patients from her universe to understand directly the complexity, unmet need, and frustration of patients.
4. Senate Majority Leader Harry Reid, my senator, advocated for ME/CFS patients at the highest level this week, and I am deeply grateful. He and Senator Kay Hagan were instrumental in raising the seriousness of patients’ unmet need and elevating the importance of a strong FDA Stakeholders Meeting for our future. I know many other Senators and Congresspeople engaged, and that is important to our future efforts.”

The hunger strike ended on day 11.

More specifically, it involves Bob Miller, 54, who is on a hunger strike. Miller stopped eating about the same time my obituary showed up, in protest of the FDA’s refusal to approve Ampligen (rintatolimod), the Toll like receptor 3 modulator for CFS that was given an unfavorable review by the FDA’s advisory panel in December, which I covered.

I talked with Miller by phone Tuesday. He lives in Reno, Nevada, because that’s the headquarters of the Ampligen trials. Miller sounded weak but determined. He choked a few times, when the subjects of his wife and twin sons, age 12, came up.

An Email Doppelganger

OK, let me get the obituary thing out of the way. Like most people with a handful of things going on at once – and like a lot of people who are simply self-absorbed – I’ve put my name in a Google alert, because I want to know if somebody online mentions me or one of my projects.

You’ve probably guessed the next part.

Delivered via Google alert, the obituary had everything spelled right (no “U” in my last name, like a lot of people tend to add. Not related to that guy!), but it got the age wrong (58, nope. One more year to go, why rush things?).

Of course, I’ve gotten Google-alert obituaries of “myself” before. I always read them, if only to find out what this other guy with my name was like, and at what age he died. Sometimes, I try to imagine myself into deceased person’s life. This latest one had been a coal miner in Kentucky for 15 years.

By Another Name, the ‘Gom-Boo’

Nobody knows what causes CFS, so I asked Miller, who’s been sick for 30 years, how his disease first manifested. He said he developed flu-like systems that would not go away. His co-workers passed it off as what they called the “gom-boo,” the name for any of a number of infections they picked up in the moist, black-dusty, oxygen-deprived environment where they worked.

Miller was a coal miner in those days, he said.

I registered the coincidence mentally, and went on with the interview. Heard how Miller, after the coal-mine job ended because of his absenteeism, could not hold down employment. How he became bedridden. How 17 years passed before he saw a doctor who diagnosed his CFS.

‘The FDA Has the Power’

Gone are the days when CFS was considered a “fake” disease, masking laziness or a person’s failure to take vitamins. I knew the horrid roster of CFS symptoms. Here’s how they are expressed by Wikipedia and others: post-exertional malaise; unrefreshing sleep; widespread muscle and joint pain; sore throat; headaches of a type not previously experienced; cognitive difficulties; chronic, often severe, mental and physical exhaustion; muscle weakness; increased sensitivity to light, sounds and smells; orthostatic intolerance; digestive disturbances; depression; and cardiac and respiratory problems.

At the FDA advisory panel meeting, a parade of people testified about CFS, and the dire need for a drug like Ampligen that seems to work. Except that there aren’t any drugs like Ampligen.

“The FDA has the power to be able to do this,” Miller said. “The company is willing to sit down with the FDA, sit down with anybody, and trying to figure out how to move this forward, without the drug company going away,” since it lacks the money for much more clinical work, which the agency wants.

Against the Odds

As the interview came to close, after I thanked Miller for talking, he asked, “What was your name, again?”

I told him. There was a two-second pause. Quietly, Miller said, “I knew a Randy Osborne when I worked in the coal mine.”

The same one, it turned out. Miller had not seen him in years.

And so I ended up breaking the news of my namesake’s death to his previous co-worker and, likely, friend. (It’s not easy to work in a coal mine, I would imagine, without becoming friends.) I broke the news to a man who may die himself, as a result of his hunger strike. He’s already been given saline for kidney problems caused by the fast, but has vowed not to take food until Ampligen moves forward, for the sake of himself and as many as a million other patients in the U.S.

I told my girlfriend about the interview, and the identical names, and the coal-mine connection. “What are the odds?” she asked. Over the past few days, I’ve been thinking about other odds. Of Ampligen finding its way to patients, somehow. Of Miller making his point, before time runs out.

The article “Biotech Firms, Billions at Risk, Lobby States to Limit Generics” slams biotechs for encouraging states to adopt legislation limiting the automatic substitution of biosimilars, which the Times repeatedly called “generics.” As BioWorld Today reported, most of the bills being considered by states would require physician notification of what was substituted, enhanced recordkeeping and an opportunity for doctors (and, in some states, patients) to decline a substitute. They also would restrict automatic substitution to interchangeable biologics.

The recommendations are not out of line. When prescribing a small-molecule drug, doctors can specify no generics. Why should it be any different with biosimilars? The FDA, after all, has made it clear that biosimilars are NOT generics. Although highly similar to a reference biologic, biosimilars are not always interchangeable.

For one thing, biosimilars may have minor differences from the reference biologic, so they may not be approved for all the indications of the originator drug. They shouldn’t be used off-label for those unapproved indications, Sherman said. Her worst nightmare would be for a formulary, seeing a big price difference, to treat biosimilars as it would a generic and switch everyone from the reference biologic to the biosimilar, regardless of the indication.

To be deemed interchangeable, and thus eligible for automatic substitution, under the unique two-sided approach laid out by Congress, a follow-on biologic (FOB) must demonstrate biosimilarity and then interchangeability, which means it produces the same clinical results as the reference drug in any given patient. While the FDA has yet to draft guidance on interchangeability, it has said switching trials will be necessary. The questions of how many, how extensive and how long must still be answered.

As part of its challenge in educating the public, the FDA will need to make it crystal clear which biosimilars are interchangeable and which indications have been approved for a specific biosimilar, Sherman said. The agency’s challenge is heightened by groups wanting to rush the regulatory process, so they can realize what they expect to be big savings. (In reality, biosimilars are likely to offer a 20 percent to 30 percent savings rather than the 50 percent to 90 percent discount seen with generics.)

Among regulators, the newness of the biosimilar field has led to a cautious, go-slow approach in the U.S. and other markets. Recognizing the potential to increase access to biologics, regulators want to avoid a disaster that could cancel the game.

Thus, Japan requires doctors to submit biweekly reports for every patient receiving a biosimilar for the first six months following approval. And in India, biosimilar sponsors must submit periodic safety update reports every six months for the first two years and then once a year for the following two years.

While the FDA can’t require physicians to submit reports, it is concerned about safety. Biosimilar data packets won’t reveal very rare signals, Sherman noted, so pharmacovigilance will be needed. “Patient safety is our paramount concern,” she said. When an adverse event occurs, the agency needs to know which product caused the problem.

That’s where the states come in. Since they regulate pharmacy licensing within their borders, a state can require pharmacies to notify physicians when a substitution has been made and keep records of the FOB that was dispensed. It’s all about safety.

The Times suggested that Amgen Inc. and Genentech Inc. are pushing for the state legislation – not because of safety concerns – but to protect their brand biologics from competition. What the article ignored is that Amgen, at least, is developing a biosimilar pipeline along with its partner Actavis Inc. And the Thousand Oaks, Calif., biotech has been successfully competing with numerous biosimilars in Europe and other countries for several years.

Editor’s note: Need more information about biosimilars? Check out The Biosimilars Game: A Scorecard for Opportunities, Threats and Critical Strategies, a new report by BioWorld Data. Call for details (800) 477-6307.

While the OPDP’s move is a welcome step in shutting down Burzynski’s clinical trial pyramid scheme, in which, according to some patient fundraising blogs, trial participants pay more than $100,000 to become guinea pigs for antineoplaston therapy, the letter provides little clarity regarding what is or is not a promotional claim.

The letter specifies, “This provision is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media. Rather, its intent is to restrict promotional claims of safety or effectiveness of the drug for a use for which it is under investigation and to preclude commercialization of the drug before it is approved for commercial distribution.”

However, some of the so-called violations strongly resemble claims made in countless biotech and pharma press releases posted on company websites.

For example, “ANP was well tolerated with easy manageable side effects of fatigue, skin rash, and electrolyte abnormalities and no chronic toxicities . . . These results compared favorably to radiation therapy and chemotherapy (Mandell, et al. 1999, 7 percent overall survival at 2 years and 0 percent at 5 years), but should be confirmed in phase III trials scheduled to begin in 2009.”

On the face of it, that statement seems identical to hundreds of statements made every day by other companies, so what distinguishes Burzynski’s regulation-violating promotion from permitted “exchange of scientific information?”

Clarity is on Hold

Crystal clarity on that question may be a long time coming. The biopharma community has been clamoring for the FDA’s guidance on a related question – how to use social media – for nearly two years, and the agency has answered with silence – a silence set to continue for another two-year period, under the new FDA Safety and Innovation Act.

That silence has led to a “gotcha mentality” that uses enforcement, rather than guidance, to communicate policy.

For companies that want to avoid running into trouble with their public communications, warning letters such as the Untitled Letter issued to the Burzynski Clinic are some of the only clues available as to what the regulations allow and do not allow.

Stephen King, a public affairs specialist for the FDA’s Center for Drug Evaluation and Research, offered a statement that provided a few more hints on the Burzynski case.

“The FDA takes seriously its role in assuring Americans the drugs they use are safe and effective and manufactured according to current good manufacturing practices (cGMP). The agency also seeks to ensure patients who are participating in clinical trials and expanded access programs are appropriately protected,” King said. “To date, no randomized, controlled trials showing the effectiveness of antineoplastons have been published in peer-reviewed scientific journals nor have all of the trials needed to approve antineoplastons as a treatment for cancer been conducted.”

So far, so good. But again the FDA’s communication falls short of total clarity as to why certain claims violate regulations and others don’t. In the Burzynski case, the clinic’s lack of evidence to back up its claims, and track record of plundering its patients’ retirement funds may contribute to the OPDP’s actions, but nothing in the OPDP letter actually cites false claims or misunderstanding by patients. “The totality of these claims suggest that Antineoplastons, investigational new drugs, are safe and/or effective for the treatment of various types of brain tumors indicated above, when they have not been approved for these uses,” the letter states, suggesting that the only and entire violation by the Burzynski clinic is that it said the words “safe and effective” before the drugs had been approved ‑ words which are ubiquitous in drug company statements regarding clinical trials of unapproved drugs.

“The promotion of investigational new drugs is prohibited by law and the agency is concerned BRI’s promotional claims will mislead patients about the safety and efficacy of unapproved antineoplastons,” said King, providing few hints as to how other companies should modify their language regarding safety and efficacy of their own unapproved drugs.

OPDP instructed the Burzynski Clinic to immediately cease dissemination of “violative promotional materials” for antineoplastons and to submit a written response by Nov. 1.

A company spokesman for the Burzynski Clinic, Azad Rastegar, told BioWorld, “Yes, we have received a letter from the FDA. While we don’t think we have done anything wrong, we have complied with their requests.”

They both use convoluted processes to accomplish a simple task, but the Goldberg invention still manages to keep the end result pretty simple. And while there may be some unintended consequences with both, they’re not unexpected with the absurd processes of a Goldberg machine. One look shows you what kind of mess you’re going to have if the cracker misses its mark, the parrot misses its perch, the seeds miss the bucket, the cigar lighter misses the fuse . . .

Not so with Congress. By the time all 435 representatives and 100 senators put their stamp on a bill, the legislation is neither simple nor transparent. In fact, the outcome is often so full of ambiguities that even the Supreme Court can’t agree on the meaning. And by time the federal agencies draft rules to implement the provisions of a bill, what started out as a simple, straightforward idea has been transformed into a megalo-regulatory mess that no one can untangle.

Take the crowdfunding provision in the JOBS Act. The simple idea behind it was to allow small companies to raise capital by getting a little bit of money from a lot of everyday people. But the tightly restricted provision that emerged from the convoluted congressional process is so far removed from the original idea that it’s a misnomer to call it crowdfunding. And by time the SEC drafts the rules to implement it, the provision is likely to be so cumbersome that it’s useless.

Even more perplexing is when Congress doesn’t recognize the messes it has created with its well-intentioned but over-engineered legislation. It may see the mess. It may even step in it. But rather than tracing the problem to the cause, Congress instead goes through its drawn-out process of hearings and finger-pointing to develop more legislation and even more regulations.

We’re seeing that with antibiotics. Citing a dearth of new antibiotics and a wealth of scary bacterial and fungal infections that won’t respond to the drugs in our current medicine cabinet, Congress added incentives to the recently passed FDA Safety and Innovation Act (FDASIA) to get drugmakers to make new infection-fighting drugs. But never once did Congress look at the legislative contraptions it has already created to see if they were in any way responsible for this life-threatening problem.

Consider this. Last year, Dificid (fidaxomicin, Optimer Pharmaceuticals Inc.) was the first new Clostridium difficile-fighting drug approved in more than 25 years. Hmmm, more than 25 years. Say, isn’t that when Hatch-Waxman lifted the floodgates for cheap generics? Could there be a Rube Goldberg connection?

Just follow the chain reaction: Hatch-Waxman opens the market to generic copies of old antibiotics. The price of antibiotics goes down, way down. Reimbursement rates are set to reflect the cheaper price of generics. Hospitals buy the cheap generics. Drugmakers stop developing new antibiotics because there’s no market for drugs that cost more than the cheap generics. The pathogens that hang out at hospitals become more and more resistant to the cheap generic versions of antibiotics, many of which have been used for half a century or more. Hospital-acquired infections become a growing threat, with few new drugs to treat them. Congress passes FDASIA to spur the development of innovative antibiotics. That law gives the Department of Health and Human Services two years to develop rules to implement the incentives and come up with a list of pathogens the new drugs must target.

Then the real work begins. And maybe, in another decade or so, we’ll have a lot of new antibiotics aimed at the pathogens we’re fighting today.

A hunter walks into a bar and says, “Did you hear the one about the FDA?”

“You mean the time it shot itself in the foot?” the bartender responds.

“The left foot or the right foot?” another hunter asks, wiping the beer froth from his mouth.

“What difference does that make?” the first hunter asks.

“I want to know if it’s the one I’ve heard before. Or if this is a new one.”

The first rule of thumb for hunters is to know what they’re doing. Otherwise, they might shoot themselves in the foot – or worse. The second is to get a valid hunting license. The third is to make sure they don’t target animals that aren’t in season.

The FDA broke those rules when it set out to track down a few scientists who it claimed had gone rogue by sharing concerns about device approvals with members of Congress and the White House. The agency tried to get a license. “No way,” it was told by the Office of Inspector General. “That dog just won’t hunt.”

The FDA, being the FDA, decided it didn’t need a license. It loaded its guns, set its snares and hired a document-hunting outfitter to help it bag its trophies. The agency reportedly gave the guide a list of the targeted species and provided scents to sniff out along the document trail. Those smells led to the media and a few hound dog congressmen and their staffs – species that should be on every federal agency’s “do not hunt” list.

The hunters at the FDA justified their poaching by saying the scientists were fair game because they were leaking information, some of which could be proprietary. Those leaks could damage the agency, its mission and its reputation, they reasoned.

Intent on catching the big game and defending its unlicensed hunt, the FDA forgot to set the safety on its weapons. As a result, the outfitter tripped and misfired, publicly posting a database with the contents of all the document tracking, including the proprietary stuff and the scents used to mark the trail. The shot hit the FDA square in the mouth and left a gaping, oozing wound in its reputation.

Now, the FDA’s the prey. And these days, it’s looking a lot like a limping deer caught in the intensely hot headlights of Congress and the media.

I politely inquired whether he had considered dieting and exercise, which could produce similar results without the potential side effects of a prescribed drug – especially one in a category that’s been dogged by cardiovascular risks.

“That’s just too hard,” my uncle replied, with a mixture of helplessness and disdain.

Sadly, that’s exactly the attitude parents seem to be passing on to their children, and the results have been catastrophic.

Last week, the journal Pediatrics published Prevalence of Cardiovascular Disease Risk Factors Among U.S. Adolescents, 1999-2008, which provided a sobering look at the twin epidemics of obesity and diabetes in teenagers.

Authors Ashleigh L. May, MS, PhD, Elena V. Kuklina, MD, PhD, and Paula W. Yoon, ScD, MPH, of the U.S. Centers for Disease Control and Prevention in Atlanta concluded that obesity in the teenage population was unchanged, with one in three adolescents between the ages of 12 and 19 officially overweight or obese, with a body mass index of 25 to 30 or greater than 30, respectively. That figure is shocking in its own right.

But the horrifying change was a doubling in the prevalence of prediabetes and diabetes in teens over the same period, from 9 percent to 23 percent, along with cardiovascular disease risk factors formerly seen only in adults.

Really, parents? What part of this picture do you not understand?

Diabetes is a devastating chronic condition that can cause life-changing complications such as nerve damage, blindness, amputation, kidney damage, heart attack, stroke and, of course, death. And unlike the pounds that can be shed from an overweight teen, diabetes is irreversible and incurable. It’s a life sentence.

What’s the best prevention for Type II diabetes, which results from lifestyle factors and accounts for more than 90 percent of cases of the disease? Not a pill or a shot, but simple exercise and a diet that maintains normal body weight.

No right-minded parent would push their child in front of a moving train, but that’s exactly what many parents are doing when it comes to the health of their children. It’s hard – but not too hard – to fix that. Trust me. I raised two teens and I’ve heard all the excuses.

For starters, get them off the couch before their only muscles are located in the fingers that do their texting. Make them walk the dog, cut the grass, take out the trash and ride a bike. Even better, encourage them to play soccer, swim, or run track. I started jogging at the age of 40 with my 12-year-old daughter, who wanted to make her middle school basketball team. It’s turned into a family pastime.

Substitute milk or water for soda. Treat French fries as a luxury instead of a staple. Give them carrots and celery – without the dip. Contrary to popular belief, fresh vegetables are cheap and don’t require a culinary degree to prepare. The U.S. Department of Agriculture’s ChooseMyPlate.gov offers simple tips for healthy eating on a budget.

And while you’re at it, take the same medicine, because children are smart. They watch their parents sit on their smartphones, upsize their burgers and guzzle their mocha Frappuccinos, and believe those habits signify adulthood. Instead, many children are slowly being steered into a lifetime of blood sugar monitoring, special diets and medications – and that’s if they’re lucky enough to avoid the more dreadful complications of diabetes.

Which brings me back to my uncle. It’s one thing for a 60-something adult to pack on 50 extra pounds and become a ticking time bomb, all the while hoping the approval of Qnexa, Contrave  or lorcaserin will avert an explosion. It’s quite another for an adolescent to face the same potential fate.

Parents need to step up to the plate, and make it a healthier one, at that. The future of our children is too important to abdicate this responsibility to ignorance or indifference.

President Barack Obama still has a glimmer of hope for preserving his Affordable Health Care for Americans Act and even if that is struck down, he can still overcome his supreme pranking with a wily November trick-up-his-sleeve snappy comeback. And Illumina Inc.’s stockholders continue to resist drinking Roche’s undervalued Kool-Aid unless they add more sugar to sweeten to Illumina’s taste. So, to the would-be biosimilars drugmakers – with no prospect of launching a biosimilars market for yet another year – April Fools’ greetings: you are the winners!

U.S.-based drugmakers hoping to produce biosimilar therapeutics were fooled into thinking they could be in the bio-follow-on business in 2012, but lo and behold, they are only one year deeper into a potentially years-long wait for a plan to actually be implemented that would allow for sales to commence. The joke’s on them – again!

After more than a decade and counting, the brand makers are still the masters of pranking.

It’s Not Rocket Science – It’s Even More Complex:

It’s Biosimilars!

Biotech has finally met its match. After revolutionizing drug development; after staring down unmet and underserved diseases; after outlasting the raging economy; after overtaking pharma in the clinic; after towing the FDA into the 21st century, the superbio-market has met its Kryptonite. Evidently, biosimilar production is just too complicated for the innovative industry in the U.S.

Doctors want them, patients demand them, the Obama administration mandates them, pharmacies fancy them and insurers covet them.

But the market pathway is apparently unsolvable, at least in the U.S. It’s War and Peace mixed with quantum physics, written in Yiddish and with the audio book narrated by the Fran Capo, the world’s fastest talking woman!

Don’t mess with the brand lobby. They may not yet be as adept as the oil lobby is in keeping the biofuels market down to fumes and fuming for a century, but they’re off to a good start. It has been more than a decade since this endeavor began in bright-eyed earnest and the brand-makers are still enjoying unchallenged market access to their exclusive reigns by perpetuating the work-in-progress status of biosimilars in its largest market country.

Biosimilar legislation was passed in the European Union (EU) in 2005 and since 2006 there have been 18 biosimilars approvals by that agency. Why, just a year between legislation and production – can you believe such impetuousness? Why, millions must be dying from recklessly putting such sketchily investigated drugs on the market!

For Puck’s sake, there is a template! By 2009, at least 15 countries, the EU and the World Health Organization had drafted final biosimilar guidelines ahead of the U.S. Canada, not exactly known for being cocksure, approved its first biosimilar (Omnitorpe) in 2009 – wait for it – in advance of final guidance for the regulatory pathway. That decision was based on its regulators’ assessment that they had existing authority, under Canada’s food and drug regulations, to approve biosimilars established on an abridged set of data than was submitted for the brand product, without the need for new regulations. What a bold concept!

I checked with BioWorld’s Washington editor, Mari Serebrov, who has been following the regulatory hoopla closely. She pointed out that “In many ways, the world is not waiting for the FDA to lead the way.”

Following such examples doesn’t guarantee safe and effective biosimilars in the U.S., but it does offer evidence that transitioning from biosimilar bureaucracy to actual commercialization isn’t going to result in an apocalypse of therapeutic proportions, either.

Even after establishment of a biosimilars market in the U.S. becomes a reality, the joke will still likely be on applicable drugmakers, inasmuch as the U.S. is leaning toward the market version that would require a full schedule of preclinical and clinical trials, which could make biosimilar drug development as expensive and laborious as the brand R&D schedule. That would make it difficult to offer deeply discounted biosimilars.

Legislation has passed and now guidelines have been issued, but U.S. biosimilar regulations are still an unfinished symphony and production is still a pipeline dream. The FDA is creating such a fazing series of clinical hoops for biosimilar producers to jump through, that it stands to constrain the number of companies that are moneyed enough to play the game and also raises the R&D bar for clinicians, while increasing the cost that patients will have to pay to compensate for the pricey clinical trials.

One of the elements of the Act was to facilitate lower-cost versions of expensive biotech drugs, but the eventual savings may not be as deep or come as quickly as hoped. Healthcare providers and other industry authorities say regulatory delays and the possibility of significant patent litigation could thwart the takeoff of the biosimilars market through most of this decade and wind up saving patients as little as10 percent to 20 percent off the cost of brand biotech drugs, compared to savings of as much a 90 percent on generic pharmaceutical drugs.

The big finale prank-in-waiting, according to Mari’s insight, could send the biosimilars movement backpedaling to square one, inasmuch as if the Supreme Court throws out the entire healthcare bill, the biosimilars snail express would be discarded in the mix, since the AHCA granted the FDA the authority to create the biosimilar pathway in the first place. Healthcare reform bill repeal would render the biosimilars guidance nonexistent as well as rendering the biosimilars developers fooled twice in the same year!

One small step for biosimilars; one giant extension for brandmakers.

Though we have only biosimilar path guidance in 2012, hope abounds for 2013 – but no promises. When biosimilars are eventually approved, they’d better be under a perfect system, as that will be the only way to justify its long and winding road. Meanwhile, biosimilar lobbyists and drugmakers, you are the 2012 April Bio-Fools – again – for the 10^th time! And your names are already on the list for the 2013 competition.

That principle has served the nation well for nearly 250 years. But now the FDA is seeking a congressional blessing to change it, under the guise of drug safety. Testifying before a House subcommittee last week, the FDA’s Janet Woodcock noted the stress placed on the agency because it bears the burden of proof when it comes to the safety of imported drugs.

Basing her request on “what other countries do,” Woodcock said the FDA needed the authority to require companies to prove their products are safe before they are allowed to cross our borders. In other words, the FDA would assume every company sending products to the U.S. is guilty of violating its standards and regulations. It would be up to the company to prove its innocence.

Woodcock’s testimony seemed to fall on sympathetic ears, as members of the subcommittee shuddered at the possibility of another heparin fiasco. No one questioned the constitutionality of moving the burden of proof from the government to the individual or company, which essentially would make the FDA the police officer, prosecutor, and judge and jury on drug imports.

Neither did they question the FDA’s justification for changing the linchpin of the U.S. judicial system. Yet any parent could tell them that “everyone else is doing it” is rarely an acceptable excuse.

Yes, drug safety can be a life-threatening issue. But it can be addressed without selling out our nation’s foundational principles. For starters, Congress could give the FDA the resources and tools it needs to police the nation’s drug supply. It could require inclusive pedigrees for every drug sold in the country. It also could require the FDA to inspect foreign manufacturing facilities as often as it does domestic plants. (Currently, the agency is required to inspect U.S. facilities every two years, but Congress has mandated no time frame for foreign inspections.)

The FDA could take some action on its own, too. It could adopt a risk-based approach to inspections. It could hire inspectors who are fluent in Chinese and other relevant foreign languages. And it could require, as part of the job description, all inspectors to do some overseas duty. (Current union contracts restrict the agency’s ability to send inspectors overseas.)