Bienvenue

Generics outfit Sandoz has achieved another milestone with the approval of Omnitrope in Canada. On April 20th 2009, Health Canada granted a Notice of Compliance for Omnitrope, making it the first Subsequent Entry Biologic (SEB) to be approved for sale in Canada. For those unfamiliar with the lingo, SEB is the regulatory term used by Health Canada equivalent to "Biosimilars" in Europe or "Follow on Biologics" in the USA.

Omnitrope, a somatropin (rDNA origin) for injection, is approved for the long-term treatment of children with growth failure due to an inadequate secretion of endogenous growth hormone, and long-term replacement therapy in adults with growth hormone deficiency due to an underlying hypothalamic or pituitary disease or who were growth deficient during childhood. With this authorization, Omnitrope carries the reputation of becoming the first biogeneric product to be approved in Europe, USA & Canada. The market authorization was based on quality, non-clinical, and clinical information submitted. Details about the studies found here.

Whilst the debate over cost savings versus quality continues to intensify between regulatory bodies and law makers, it is encouraging to see products trickling through a system whose effectiveness cannot be evaluated unless it is put into practice. , the current system (however skeletal it may be) needs to be tested in order to:
1)Define the parameters of substitution of biosimilars for innovator products;

2)Determine the extent of pre-clinical studies & clinical trials required to demonstrate safety and comparability;

3)See whether true copies of biologics can be made despite the original products being covered by extensive trade secrets, patents and proprietary technologies;

4) Test the financial sustainability of biogeneric manufacturers. The development of each biogeneric product will be a lengthy, complex process, and is projected to cost about $200 million, compared to approximately $30 million for a traditional generic drug;

5) Quantify the extent of cost savings and the impact of competition on cost reduction;

6) Gauge consumer confidence and acceptance.

It is clear that regulations for biosimilars or follow-on biologics will be implemented in the near future. However, What remains to be seen is whether political pressure from influential groups and an extremely cautious approach on the part of the legislators can be balanced out to develop a functional pathway to approval.

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Innovation Update

A Boost for Protein Expression:

Invitrogen has launched its GIBCO®OptiCHO Protein Expression Kit - the first kit of its kind to provide cells banked under cGMP conditions, enabling biotherapeutics manufacturers to speed regulatory submissions and time to market. The cell line development kit will provide not only the cGMP parental cells but also the components and all the protocols needed to engineer and select producing clones in a completely serum-free system. Amongst other things, cGMP requirements for production cell lines derived from parental cells include source verification, testing, history, control over cell production documentation, and ability to demonstrate chain of custody for the cells from creation through use in biotherapeutic production. Costs for testing & project management to meet these GMP guidelines can range from $30K to $50K - a significant amount for research labs.

The real kicker in this story, however, is the potentially game changing move of providing a single-fee commercial license with no royalties. Taking into account that current procurement costs for a research or commercial use license have been reported to range from $7,000 to $50,000 per year for research use licenses, and up to $500,000 per year (plus royalties on the therapeutic product) for commercial use licenses, Invitrogen’s attempt at market penetration may have a big effect on the balance sheets of cash strapped start-ups. In addition to the cost savings on licenses, royalties, documentation, & regulatory activities the GIBCO kit may also reduce productivity problems. In order to improve biosafety & regulatory approval timeline, many researchers have been removing serum and products of animal origin from cell-culture media during production of therapeutic proteins from CHO cells & using plant hydrolysates as nutrients. The drawback of using plant hydrolysates is that they often contain undefined levels of nutrients and can result in lot-to-lot variation in fed-batch performance and purification inefficiency, which are disadvantages when consistent protein yields are required. To solve this problem, the new kit makes use of chemically defined feeds which apparently not only eliminates the variability associated with using plant hydrolysates, but could also improve the productivity of biopharmaceutical protein manufacture and help move therapeutic proteins into clinical trials more rapidly.

Efficient Eye-Screening:

Using a technology originally developed at the Department of Energy's Oak Ridge National Laboratory to understand semiconductor defects, people at risk of becoming blind can now be screened for eye diseases such as diabetic retinopathy and age-related macular degeneration. The technology involves taking pictures of the retina and relaying them back to a database for comparison. Comparison with thousands of images of known retinal diseases, will determine if the patient passes the screening or is in need of follow-up care.

Manufacturers of semiconductors have used this technology for over a decade, to rapidly scan hundreds of thousands of tiny semiconductors to learn quickly about problems in the manufacturing process. "Right now, with 21 million diabetics in the United States, we need to be screening 400,000 patients for diabetic eye disease every week. Less than half of these diabetics receive the recommended annual eye exam, which is absolutely essential to minimize serious eye complications and potential blindness." says Edward Chaum, who is leading the medical portion of the project. Utilizing an automated process of this kind has the potential to not only improve ophthalmic care in rural areas but also reduce the burden on outpatient clinics & primary care physician offices in urban centre’s. The goal is to have hundreds of cameras installed in the US and beyond, for early detection of disease in a cost effective manner.

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Of mice and men ...

On March 4, 2009, the U.S. Supreme Court issued a 6-3 majority decision in Wyeth v. Levine, No. 06-1249 against the pharmaceutical giant. The Court held that the Food and Drug Administration's (FDA) prescription drug labeling judgments, and specifically, its approval of the label for Wyeth's Phenergan, do not preempt state law tort claims alleging inadequate warning. At issue was a lawsuit by Vermont guitarist Diana Levine, who lost an arm to gangrene after Wyeth’s antinausea drug Phenergan was INADVERTENLTY injected into one of her arteries during a push IV injection. Ms. Levine had gone to a clinic for treatment of a migraine headache. Ms. Levine argued that Phenergan’s labeling, though approved by the Food and Drug Administration, didn’t provide proper warnings of the risk of administering the drug through a push IV injection instead of using an IV-drip.

For those following the case over the past few months, it was evident that heads would turn regardless who the court ruled in favour of. But few were expecting the decision to go against Wyeth, especially since the courts had ruled in favour of pre-emption in a similar case involving a medical device (see Riegel vs Medtronic). Ultimately, what it came down to was the presence of explicit wording in the Medical Devices Act saying “no State ‘may establish or continue in effect with respect to a device . . . any requirement’ relating to safety or effectiveness that is different from, or in addition to, federal requirements …”. Nothing of that sort is present in the Food, Drugs, and Cosmetics Act. So why did Wyeth’s legal team even consider pre-emption to be a plausible defense? Apparently the FDA was in the mood for an ol fashioned power trip in a preamble to a 2006 regulation the agency issued on prescription drug labeling. This included statements that the agency can indeed pre-empt state law as they provided for not only a floor but also a ceiling to such labeling language, and so on. Wyeth seems to have relied a bit too heavily on this preamble. So this decision might look like a whack at the drug industry, but it's actually a case of a federal agency being told that its powers aren't as broad as it occasionally seems to think. You wouldn't necessarily guess it to see that way the justices lined up in this case, but the verdict looks like a real endorsement of federalism. And in the same way, you might not guess it, but the drug companies would probably like for the FDA to be that powerful, actually - that way, some of the responsibility could be offloaded, and there would be a single place to go for regulatory clarity.

Of equal importance and worth mentioning is that this unfortunate incident could easily have been avoided but for the EMT’s negligence in administering the drug in a way the manufacturer did not intend. This litigious society is going down the toilet. Obviously, Ms Levine should be compensated, but by those who made the mistake, not by those who provided the cure, that when administered properly would have helped her, not harmed. I cannot help but think the main reason they went after Wyeth is because Wyeth is seen as the party with the deepest pockets. This is not to say that Wyeth was completely devoid of fault. The bigger issue is clearly whether or not it is pharma’s responsibility to provide adequate warnings in conflict with FDA approval. As it stands, and regardless of what the FDA says, the burden of proof is not on the FDA to prove harm, but rather on the manufacturer to prove its product is safe. The FDA warning requirements provide a “basement not a ceiling” - e.g., the manufacturer has some responsibility to update its labels and warnings over time, when more evidence is obtained as to the safety or danger of its products.

Preemption has a place but not in this case and not with these facts. That Wyeth could have requested a label change to reflect its growing awareness of possible heightened risk from certain routes of administration is incontrovertible. That Wyeth claimed that it could not have done so flies in the face of reason and past experience. None of this suggests, however, that a good case cannot be made for preemption. This just wasn’t that case. The facts were not on Wyeth’s side. All this is simply to suggest that I don’t think this is the last we’ll hear of preemption or the last the Supreme Court will have to say on the doctrine.

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The 28 day round-up

Despite the rumblings of layoffs, downturns, redundancies and bailouts, February seems to have been a good month for drug approvals globally. Following are some noteworthy developments.

-Matrix Labs received the first and only World Health Organization (WHO) approval for Lopinavir/Ritonavir Tablets, 200 mg/50 mg. Matrix's version of this product is heat-stable and affordable, making it practical for distribution and use in warm climates. A WHO approval indicates that a drug meets international safety, efficacy and manufacturing quality standards. With such status, Matrix can sell the treatment in most countries outside the United States and Europe. The company's emphasis on producing affordable products has allowed it to drive down the average annual cost per patient of effective therapies. Approximately 30% of HIV/AIDS patients in the developing world depend on Matrix's ARV products.

- The US FDA has approved ATryn® (Antithrombin [Recombinant]) for the prevention of peri-operative and peri-partum thromboembolic events in hereditary antithrombin deficient patients. The GTC Bio & Ovation Pharma collaboration is the first ever transgenically produced therapeutic protein and the first recombinant antithrombin approved in the U.S. Along with the approval of ATryn, the FDA’s Center for Veterinary Medicine also approved GTC’s New Animal Drug Application, the first of its kind for the regulation of a genetic construct stably integrated into the genome of genetically engineered animals. This is now required for a recombinant technology used to develop transgenic animals, such as the goats that produce recombinant antithrombin.

-Good news for patients with osteoarthritis of the knee. The FDA has finally approved Genzyme's Synvisc-One which could potentially change the face of viscosupplementation therapy. Viscosupplementation is a procedure in which hyaluronic acid or a derivative such as hylan G-F 20 is injected into the knee joint to replace synovial fluid that typically becomes degraded in patients with osteoarthritis. Synvisc-One is an important therapy for OA of the knee because it delivers long-term pain relief (upto 6 months) through a single injection without the systemic side effects that can be caused by steroids and anti-inflammatory medication.

-Over 5 million gout patients with hyperuricemia have a new treatment option for the first time in 40 years. Teijin Pharma's new molecular entity, Febuxostat, is licensed to Takeda for marketing in the US where it will be available as ULORIC.

- The European Commission has granted marketing authorisation for Servier's Valdoxan(R) /Thymanax(R) (agomelatine), the first melatonergic antidepressant for the treatment of adult patients with major depressive episodes. Valdoxan is the first antidepressant with melatonin receptor (MT1) and (MT2) agonist properties and 5-hydroxytryptamine (serotonin) receptor 2C (5-HT2C) antagonist properties. This unique receptor profile of Valdoxan allows for the first time the restoration of the circadian rhythms of depressed patients. Valdoxan's mechanism of action is unlike those of the commonly-prescribed antidepressants, the SSRIs and SNRIs, as Valdoxan exerts its antidepressant efficacy without having an impact on serotonin levels.

-Dapoxetine has received marketing authorisation in Finland and Sweden for the on-demand treatment of premature ejaculation (PE) in men 18-64 years of age

-A big bump for companies in Canada, as some potential major earners received approval. The 44 NOC's issued by Health Canada included- Lilly's Cymbalta for Generalized Anxiety Disorder; Schering Plough's much anticipated contraceptive NuvaRing; Shire's Vyvanse for ADHD; Wyeth's antidepressant Pristiq; and a new indication for Avastin by Roche. The increasing number of drug submissions in Canada is a sign that manufacturers now consider the Canadian market to be substantial and profitable enough to hit those earning targets despite price controls, a public payer system, and generics friendly IP laws.

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Travesty Within Tragedy

For those of you who haven’t really had much sympathy for Madoff fraud victims, here’s some food for thought. It seems that at least 147 foundations had all their assets invested with Big Bernie – money that was to be allocated to several non-profits, charities, research & social projects - further proof that there is no room for sustainable philanthropy in traditional Laissez-faire economics.

In addition to significant cutbacks in securing any sort of traditional funding, healthcare research & science initiatives may well be forced to go on hiatus or depend solely on government funding. Here are some of the notable victims (direct & coincidental) with ties to life sciences:
- The $1 billion Picower Foundation of Florida, whose beneficiaries include a neurological research institute at MIT (led by nobel laureate Susumu Tonegawa), children’s health fund, a planned parenthood group, and Parkinson & diabetes research at UPenn.
- The $1.75 million Auld foundation of Seattle, supporter of the Seattle biomedical research institute.
- The $15 million Elie Wiesel Foundation for Humanity - Over $5 million of the Shapiro Foundation donations to various health & human services.
- The Fiterman Endowment Fund for Digestive Diseases.
- The Gift of Life Bone Marrow Foundation which is now $1.8 million short of its projected annual budget.
- North Shore Long Island Jewish Health System which had a $5.7 million gift invested with Madoff.

Madoff's absence of integrity is no longer shocking, but what continues to strike me is how such a sociopath can gain such an immensely deep level of trust within a circle valued for its smarts (arguable), without ever being questioned. Even more sickening, is the lack of due diligence and the level of laziness & stupidity demonstrated by the above mentioned foundations. Not only do they decide to invest all assets in one basket, but what exactly were the board’s upto? To quote a comment on a blog - “Were these boards having investment advisors come in monthly or quarterly and explain exactly where the funds were and how they were diversified? And questioning why they were not riding the market more instead of such fabulously steady returns?”

Private foundations are too often treated as extensions of the founder’s estate - to be managed with the same care or lack of care - when by law they are separate entities obligated to serve the public good. The losses of these foundations are the public’s losses, and it’s important to remember they were funded 1/3 or more by the U.S. Treasury through tax deductions. In the wake of this scandal perhaps the best option is to limit the types of investments & securities that can be held by foundations & pension funds, in order to secure and to maintain their exempt status.

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Dapoxetine: The Final Blockbuster?

Janssen-Cilag (a Johnson & Johnson company) announced on Feb 10 that it had received regulatory approval in Finland and Sweden for its dapoxetine drug Priligy™. These approvals follow the December 2008 decentralised marketing authorisation procedure adopted by seven European Union countries: Sweden, Austria, Finland, Germany, Spain, Italy and Portugal. The two Scandinavian countries can now boast another claim to fame: being the first nations to offer their men an approved treatment for Premature Ejaculation (PE).

Dapoxetine hydrochloride is a novel, selective serotonin reuptake inhibitor (SSRI) compound that last made headlines in 2005 when the US FDA declined to approve the drug for PE. The reasons cited back then were lack of sufficient evidence and side effect issues. Dapoxetine has now been extensively evaluated in five randomised, placebo-controlled Phase III clinical trials involving more than 6,000 men with PE and their partners. More details about that here. J&J hopes that their comprehensive trial programme pays dividends, and has applied for market authorization in the other 5 European nations with a decentralized system as well as 10 other countries, including Canada, Australia, Mexico and Turkey. Successful approval in these markets may well mean that it is only a matter of time before the FDA is faced with a second review of dapoxetine.

So why the big fuss you ask? Well, according to a well publicized 2005 study in the Journal of Sexual Medicine, PE is the most common male sexual dysfunction affecting between 20-30% of males (It just so happens that the study was funded in part by J&J and its subsidiary Alza). Nonetheless, it is a legitimate condition that millions suffer from, and at a time when pipelines can no longer cater to blockbuster categories, J&J finds itself sitting on a golden cash cow. The US erectile dysfunction (ED) market (Viagra, Cialis and Levitra) was $3.4 billion in 2007 and continues to grow; according to industry analysts, the market for PE drugs is estimated to be as large as the erectile dysfunction market. In contrast to ED, which is more prevalent in men over 50, PE is a problem encountered by sexually active men of all ages. Importantly, there is no major competition being faced as both Pfizer & GSK abandoned their candidate drugs after the FDA rejection in 2005. A Massachusetts company – NeuroHealing Pharmaceuticals- has a d-modafinil (of Provigil fame) isomer in development for PE, but they don’t expect to commence clinicals until early 2010.

Even more astonishing (and a testament to J&J’s superior deal-making capacity) is that the rights to dapoxetine were bought for a meager $65 million. Dapoxetine (originally known as LY 210448) was one of David Wong’s creations (others include Prozac, Cymbalta, Stattera) in the late 80’s when Eli Lilly actively began pursuing the depression market. However, after several failures, Lilly sold the patent to J&J in 2003 subsequent to their purchase of Alza. Although it is known that high serotonin levels do play a major factor in lengthening ejaculatory response, off label use of currently approved SSRI’s in treating PE have been largely discouraged due to the side effects such as ED, loss of libido, nausea, serotonin syndrome, and increased suicide risk. The beauty of dapoxetine however, is its very short half life of 1.2 hours, meaning men can take the medication on demand with low risk of accumulation.

Whether dapoxetine is effective or if it will be a successful product are no longer valid questions. In a post Viagra world, it is almost certain that it will achieve near-cult status. The real question is whether dapoxetine’s success will be its eventual downfall. Not unlike the COX drugs, the potential for flagrant prescribing of dapoxetine is high. Combined with what will certainly be a high rate of abuse, it will be interesting to see what medical precautions & dispensing limitations are placed. One thing is for sure, a dapoxetine tragedy can not be blamed solely on the manufacturer. This time around, the entire medical community will have to shoulder the responsibility.

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Canadian Brain Drain to continue

The Canadian science community, hoping to harness energy from the southern winds of change, had some long faces as the Federal Budget was announced on January 28. As President Obama finds momentum for his $16 billion radical cash infusion into R&D, innovation, and academic infrastructure, the Canadian conservative government seems to be of the opinion that scientific research should not cost so much and investing in the blue collar economy is the best way to get out of recession. So lacklustre was the 2009 budget that the biggest headline seems to be a 15% Temporary Home Renovation Tax Credit! For all the Conservatives reading this – No, I have not forgotten about the miserly TFSA or the extra $500 you will save on taxes only to be ripped off at the gas stations. I am glad you lot are so easy to please. But, I digress – lets stick to what has been allocated to life science initiatives.

Here are the numbers:
• $750 million for the Canada Foundation for Innovation (CFI)
• $500 million for Canada Health Infoway
• $87.5 million for Canada Graduate Scholarships disbursed by NSERC, CIHR, SSHRC (over 3 years)
• $3.5 million for Industrial Research and Development Internship program (over 2 years)
• $200 million for the NRC Industrial Research Assistance Program (over 2 years)
• $250-million for deferred maintenance at federal research labs (over 2 years)
• $2 billion to “repair, retrofit & expand” infrastructure at universities & colleges.
• $80 million for Transformative Technologies program
• $1.5 billion each to Export Development Corporation & Business Development Bank of Canada.
• The taxable income threshold for refundable Scientific Research & Experimental Development (SR&ED) tax credits increased from $400,000 to $500,000

Where is some of this money coming from you ask? How about:
• $27.7 million cut from the NRC budget
• $147.9 million cut from the NSERC, CIHR, SHRC (over 3 years)
• $167.8 million cut from Health Canada & Public Health Agency of Canada (over 3 years)
• No new funding for Genome Canada

Upon initial review, one could say that it is a surprisingly decent “stimulus” package to spur on the knowledge based economy. But like most things in our society, the fine print always makes us cringe. Most of the increased funding comes with significant caveats, while the rest comes simply through re-allocation of funds from the total organisational budget to more focused initiatives.

For instance:
• The $2 billon earmarked for infrastructure projects can only be allocated if 50% of project costs are funded through other sources. Yet another great excuse for universities to raise tuition.
• Of the $750 million received by the CFI, $600 will be reserved for new competitions in “support of areas of priority identified by the Minister of Industry”. The conservative agenda will certainly be promulgated through this minor detail (no word of course on whether this is a use it or lose it deal).
• The money for maintenance of federal labs will be used to modernize government labs that submit a “realistic business plan” for their transfer to university, business, or non-profit group. In what seems to be a precursor to privatization of healthcare, the present government is clearly divesting interest in federally funded research capability.
• The cuts to Health Canada & PHAC will be achieved through streamlining operations it seems. Now while I certainly do believe both agencies could become a lot leaner, I also believe that both are understaffed. I hope the governments “strategic review” is not innuendo for layoffs.
• The provisions made to help small & medium life science enterprises secure capital is simply abysmal compared with other nation’s plans. France has already announced a tripling of their equivalent tax credit program, Norway has created a new fund valued at almost $500 million solely for biotechnology, the UK is currently working to confirm a new national fund specific to life sciences and the US is contemplating allowing the sale of tax losses for cash infusion to small emerging technology based companies.


This is not stimulus, and it certainly is not based on forward looking public policy. It is clear that the government intends to make the disbursement of allocated monies as challenging as possible. What they don’t seem to realise is that Canada will be falling behind the rest if we continue to ignore the competitive environment other nations will be adopting to help grow and stimulate their knowledge based industries that are vital to economic recovery in both the short and long term.

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Pfizer-Wyeth: Why nobody wins

In an otherwise headline sluggish industry (lawsuits apart), the Pfizer-Wyeth deal certainly has lit up the newswires and sparked some much needed debate. The announcement of the $68 billion dollar deal was as much of a shock to some as it was the culmination of months of predictions for others in the industry. The merger is being touted as an “ideal marriage”, with the potential to save billions for both companies, as their most profitable products face patent expiration from 2011 onwards. They may have others buying into this hogwash, but I see this deal for being what it actually is – Twisted. The formation of Pfyeth benefits nobody- not the stockholders, not the employees, not consumer sentiment, definitely not drug development, and even misles the common tax-payer! Actually that is not completely true. It does benefit one person – Pfizer CEO Jeffrey Kindler. Kindler played his cards well and the announcement formed a welcome distraction from the news that Pfizer was also paying a $2.3 billion settlement to make the Department of Justice stop investigating the company’s illegal promotion of discontinued Cox-2 painkiller Bextra, and a 90% drop in income.

Kindler: "We're in a much better position to bring on board the scientists and programs and projects that Wyeth has"
The last couple of times Pfizer went appliance shopping, buying Warner –Lambert in 2000 and swallowing Pharmacia-Upjohn in 2003, it was faced with serious alignment and integration issues. Pfizer's "big corporation" image was at definite odds against Warner’s consumer health focus and there was a serious culture clash that was eventually only solved by new management. While corporate image may not be the issue at hand in this case, Pfizer thinks they can swiftly integrate an entirely new field of therapeutics! Wyeth alone with its expertise in biologics barely made it past facility inspections and product safety audits. One can only imagine the tensions in the hallways as Pfizer deploys its managers to oversee and “align” operations. Kindler mentions bringing aboard scientists, programs, and projects, he will also be bringing aboard the many lawsuits against Wyeth for the Hormone Replacement Therapy debacle.

Kindler: "In one single transaction, the combination with Wyeth advances every single one of (our) strategies,"
Really? Like the halving of stock dividend? Probably the only reason investors would consider having Pfizer stock in their nest egg post Lipitor. What about manufacturing capacity? Oh that’s right, you are shutting down 5 plants. Or maybe you are referring to sales? Together, the two companies will have 17 products with annual sales of $70 billion or more. Reasonable, but that’s only until 2012. This purchase is not transformational and as much as Pfizer would like to think that this will solve their pipeline problems, it is simply not acquiring a robust R&D model. As Derek Lowe of In the Pipeline fame says “as a research-driven company grows larger, everything scales except research productivity”.

Behind the Scenes
Despite all the above grievances with respect to this merger, there is one poorly publicized issue that troubles me the most. The deal is being financed by five banks: Bank of America Merrill Lynch, Barclays, Citigroup, Goldman Sachs and J.P. Morgan Chase. The billions that will be lent to Pfizer are coming from the Troubled Asset Relief Program (TARP) program- set up by the US government to purchase assets and equity from financial institutions in order to strengthen the financial sector. It is the largest component of the government's measures in 2008 to address the subprime financial crisis. That’s right. The money for this deal is coming from the American taxpayer! The money that will eventually be used to eliminate 20,000 jobs! So not only does Pfizer jip you on meds, but they take your money and punish you for helping? How is this right? Although meant to increase lending by banks, the only restrictions set on TARP money are that participating banks can't increase their dividends without Treasury's approval and must agree to certain limits on executive compensation. Few other strings are attached.

I am however hopeful. Hopeful that the Obama administration takes some steps in ensuring public rescue funds are used ethically, that the FTC investigates this deal closely, that Wyeth shareholders vote against this offer, and that the creation of Pfyeth does not send the industry into a desperate feeding frenzy.

UPDATE:
Pfizer currently has six Alzheimer drugs under development and one on the market, while Wyeth has four of Elan’s Alzheimer drugs and five Alzheimer drugs of its own in development. Pfizer will now control 16 Alzheimer drugs, which represents a majority of all Alzheimer drugs currently in clinical development and on the market, creating a virtual monopoly for itself.

If allowed to control all these drugs, Pfizer would undoubtedly be forced to determine which of these compounds would receive priority in clinical development and which would be slowed down. As a result, Pfizer will likely favor those drugs in which it holds a 100% interest. Ultimately, the biggest loser in this situation would be Alzheimer patients, along with their caregivers and physicians, who may have fewer treatment options available to them.

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Preemption: What is it good for?

For more than a decade, drug manufacturers in the US have been inadvertently protected from product liability claims thanks to preemption - the precedence of federal law over that of state law.

So what happens when a patient takes a generic version of a drug that results in an adverse event (or death) due to inadequate warnings? Surely the consumer is protected by being able to sue the manufacturer, correct? Apparently not. Generic manufacturers have successfully argued that they were unable to provide sufficient warning as their labels are required to be the same as the labeling approved for the original innovators drug. Additionally, a generic drug manufacturer may not unilaterally strengthen a label without prior approval of the FDA. Therefore, it "would be impossible" for the manufacturers to abide by federal law requiring that the generic have the same label as the innovator and the state-law requirements for stronger warnings. Surely then the onus falls on the innovator companies for not originally having sufficient warnings, correct? The uninformed patient may be shocked to learn that most state courts have ruled that the name-brand manufacturers could not be held liable for injuries caused by another manufacturer's product.

This is the conundrum posed by preemption. Preemption prevents plaintiffs from pursuing their claims against defendants whom they allege caused their injuries, and yet the preemption doctrine is based on a choice of the superior method for regulation. The distinct lack of a legal remedy in such cases may explain the California Court of Appeal's decision in Conte v. Wyeth.

In Conte v. Wyeth, Elizabeth Conte alleged she developed an irreversible neurological condition after long-term use of generic versions of Wyeth’s Reglan. Although she only took the generic version of the drug, she argued that Wyeth negligently misrepresented the serious risks associated with long-term use of the brand-name version of the drug and should be held liable. Conte filed a lawsuit against Wyeth as well as generic manufacturers Purepac, Teva, and Pliva. After obtaining summary judgement in trial court, Wyeth & the generic manufacturers succesfully argued that Wyeth's product information had no causal relationship to Conte’s injuries and the Conte's claims against the generics were preempted under the Food, Drug and Cosmetic Act.
The California Court of Appeals, First Appellate District, reversed in part and reinstated Conte’s action against Wyeth. Ignoring decades of products liability precedent, the Court concluded Conte could proceed against Wyeth on her negligent misrepresentation claim on the basis of common law.

Preemption is a classic example of instances where enforcing an optimal regulatory strategy does not necessarily translate into protection of the public. In the search for a one size fits all approach to streamline a process, several caveats can be left which prevent legislation from meshing with the justice system. This year, in Levine v. Wyeth, the Supreme Court will address the issue of preemption of claims against name-brand manufacturers' in what could be a landmark victory for consumers. The judgement may very well impact consumer confidence in public agencies such as the FDA and further tarnish the image of drug manufacturers.

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