Goldacre, it turns out, is as much bothered by the secrecy of data as by its quality, and he has also set up an activist website, where the public can petition for “all [clinical] trials to be registered, for all summary results to be reported, and for full clinical study reports [CSRs] to be made publicly available,” he writes on his original site, which takes its name from Goldacre’s previous book. “CSRs are important, because it is now clear that brief summaries about trials [such as academic journal articles] can be incomplete or misleading,” writes Goldacre.

I probably took so long to get through the book because I sensed that the heft text would take on “the usual Big Pharma critiques, touching on the ethical morass of human trials and the infuriating dirty tricks pharmaceutical firms use to market their drugs both to patients and to doctors,” as a review in the New York Times pointed out late last month. But there’s more to the book.

Among the firms Goldacre, a London doctor, takes to task is GlaxoSmithKline plc, which surprised the author and probably everyone else in February when the firm came aboard his cause, and agreed to post its CSRs online. “They have also made sensible noises about the practicalities, which shows that they have thought about the implications, and they also discuss prioritizing which CSRs to work on first,” writes Goldacre. (Another reason for my slow going with this book: dread of stiff British, physician-style writing and clichés. Practicalities, implications and prioritizing. “Because [GSK has] discussed these technical details – while I will always wait for the proof in the pudding – I do not believe this is mere lip service,” he goes on, wedging in a couple more.)

But, as a blunt instrument, the book seems to be having an effect. Will AstraZeneca plc join GSK? Goldacre summarily smacks down the developer of Iressa (gefitinib), a rather easy target, in his book. “Large, well-conducted fair tests of Iressa had shown that it was no better than a dummy sugar pill containing no medicine,” he writes, yet patients who turned out at an FDA advisory panel meeting sang the drug’s praises.

“When the committee charged with approving the drug [sic] cast their votes, they went 11-3 in favor,” Goldacre recalls. “We can only wonder if individuals who had not been successfully treated with Iressa would have been flown across the country to speak their personal truth. Perhaps not. Perhaps they might be dead.” Perhaps. But the issue of full trial-data disclosure, thanks to Goldacre’s book, is anything but.

The public hearing speakers, along with the usually silent patient member of the panel, seem to have one function – to let the FDA check off the box for patient involvement. But patients with orphan diseases and their families deserve more than token involvement.

After all, those patients voluntarily took what could be life-threatening risks to participate in a clinical trial. And even though a sponsor may be paying for their travel to be at the hearing, the patients and their families are freely giving their time in the hope that their voices will be heard and weighed by the members of the adcom and the FDA staff, all of whom are paid to sit through the meeting.

So why do they bother to speak up? The patients are there because they want to have a say in what clinical trial endpoints really matter and what risks are acceptable. They want their first-hand experience with a disease and potential treatments to make a difference for others who may face the same challenges in the future. And they want to ensure that the doctors who are on the front lines of treating the diseases are being heard in the regulatory process.

Instead, the patients are greeted with polite smiles and their words are dismissed as soon as they’re spoken. And the doctors are disregarded as “conflicted” because they participated in the trials. “It was so disheartening,” Dena Battle said of her first experience of testifying before an adcom. “We were sort of dismissed as just emotional anecdotes.”

Both Dena and her husband, Chris Battle, who is fighting kidney cancer, spoke in favor of approval of AVEO Oncology Inc.’s tivozanib as a treatment for renal cell cancer. Unswayed by the patients’ experience, the advisory committee spent the rest of the session scolding AVEO for its trial design.

While some mistakes may have been made with the trial, Dena said the meeting would have been much more productive had the committee – comprised of biostatisticians, breast cancer specialists, hematologists, a pediatric oncologist and a prostate cancer specialist – engaged in a thoughtful discussion with the renal specialists in the room about how AVEO should proceed with the RCC indication. Instead, “the doctors that know most about this disease . . . were all shut down,” Dena told BioWorld.

As a result, the only vote in support of the drug came from patient representative Dan Lumley. Now AVEO is facing shareholder lawsuits, and its partner Astellas Pharma Inc. has pulled out of the RCC development of the drug. While tivozanib is still being developed for breast cancer, it’s unlikely the drug will be developed for RCC, even though it showed promise in the orphan disease.

Over the next few years, the FDA is likely to devote considerable time and resources in figuring out how to implement the FDA Safety and Innovation Act provisions requiring patient involvement in the drug approval process. The first step is a no brainer: Actually listen to the patients who are trying to live with the disease. Step 2: Consult with the doctors who are the specialists in dealing with the orphan disease.

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.”

Cynics might claim it’s something the drug companies invented, so they can pump more chemicals into people earlier. But the idea, Andrews said, is to express that kidney trouble appears along a continuum, and pre-shutdown symptoms need to be handled promptly, because they create big woes on their own. Woes that might be lucratively attacked by the likes of Thrasos, with its lead compound THR-184, which is nearing Phase II.

Ransacking the BioWorld database, I found “acute renal failure” tapering off in 2008. It vanished in 2009, with the use of “AKI” rising as fast as creatinine levels in an afflicted patient, as more companies joined the race. So many that I missed one in the BioWorld Today story I wrote on Thrasos and its $35 million financing.

That would be Novartis AG, which more than two years ago tapped privately held Quark Pharmaceuticals Inc. for QPI-1002, a p53 temporary inhibitor siRNA drug that targets AKI. Novartis stepped in at the typical Phase II stage, forking over a cautious $10 million up front but promising up to $680 million more if QPI-1002 proves out. “I don’t know much about their compound, haven’t heard much,” Andrews said, also normal for pharma.

Like much clinical work, that with QPI-1002 focuses on cardiac patients, even though they represent only about 20 percent of AKI. Would-be competitors for Thrasos are doing the same: Abbott (which bought Dutch firm Action Pharma A/S earlier this year to get the Phase II AKI compound AP214) and Allocure Inc. (with ACT-AKI, a mesenchymal stem cell therapy, also in Phase II).

It’s just easier to design a trial around the cardiac patients and get “cleaner” data, compared with, say, the awful-outcome sepsis setting, which makes up another 20 percent of AKI. Drug toxicity and general surgery comprise much of the rest.

Andrews said the latest funding “better get me through Phase II, or my board will have a serious talk with me,” adding that he “fully expects” the cash on hand will pay for a dosing Phase II study and a confirmatory one.

At that point, given success, Thrasos – which means “boldness” in Greek – could find itself sprinting to the head of the AKI pack, especially if it has the luck to lure a pharma player of the Novartis or Abbott caliber to continue work with THR-184, a small peptide that selectively activates certain receptors of bone morphogenetic proteins.

Or to buy whole outfit. THR-184’s mechanism looks at least as worthy as siRNA and stem cells. AP214, the drug that drew Abbott to the table with Action, is a first-in-class alpha-MSH peptide derivative, and somewhat harder to weigh. But Thrasos’ chances look good. Come the end of Phase II, maybe Andrews will be having talks with his board about something else.

From my perspective, the study makes it even more difficult to figure out which of the many research findings that (briefly) come to my attention every day to write about, and which to ignore. Is this study more interesting, or that one? Well, uh . . . can either of them be replicated?

Authors Glenn Begley and Lee Ellis stressed that they were not out to pillory individual scientists. Indeed, the sheer magnitude of the problem indicates that this is a systemic issue that needs a systemic fix – because journals and funders are valuing perfect stories over accurate data.

In the meantime, though, one of the implications of the study is that far from being riddled with conflicts of interest, preclinical results reported by industry, may be more reliable than those coming out of academia.

This has nothing to do with who’s the better person. Or the better scientist. It has to do with timing. For an academic scientist, a paper in a high-impact journal is a happy ending, the culmination of a lot of effort. For an industry scientist, that paper is also a success – but it is the successful beginning of what could turn into a billion-dollar development effort.

This is not a new view among industry scientists. Several years ago, at a meeting, a friend from a large biotech company and I sat and listened to a speaker hold forth on recent findings that the rate of positive results was higher in papers that come out of industry.

The speaker’s point was that if industry’s rate of positive findings was higher, that was indicative of data massaging. My friend wasn’t buying, though. Instead, she rolled her eyes and snapped, “Well, maybe we run better studies!”

Before industry starts patting itself on the back too hard, let me point out that I am talking specifically about preclinical data. In industry, the problem of selective reporting gets shifted to later in the process – where you can find plenty of stories of whole arms of clinical trials suddenly disappearing from clinical trial reporting and the like.

And so, my point is not that it’s academia’s turn to wear the dunce cap. Companies want to develop good medicines, but they also want to – and need to – be economically viable. Academics want to do good research, but they also want to – and need to – be professionally viable by publishing in good journals and getting grants. Everybody has multiple goals, and the better our system of research manages to align those goals, the better the science that our drugs are based on will be – no matter where that science is coming from.

Even as the villainous economy brought drama to the world stage with its own tour de force production, the biotechnology market continued to receive generally positive-to-cautious reviews from industry critics and everyone else who had a speaking role in the market. Its performance and celebrity status have only been upstaged or matched since 2000 by its primary rival: high technology – which is led by the acting of the Meryl Streep of stock market performers: Apple Inc.

But biotech’s stock continues to rise also, thanks to its made-in-Hollywood hook-up with the winner of the Best Supporting Role in a Market Pairing: Big Pharma. Biopharma is the new Brangelina! So stick out that leg, Biopharma, and strike a pose!

After all, the script that biotech has acted out in the 21st century has mimicked the adapted-for-the-screen storyline of Stieg Larsson’s well-received Millenium Trilogy. Biotech – increasingly throughout the past decade and forecast right through this one – is assuming the role of The Market with the Dragon Tattoo, as everyone wants China in their picture. That country is the odds-on favorite to bring home the award for Best Performance in a Foreign Language Market for the next decade, as it ascends to the top of the A-list while mesmerizing the entire drug industry audience.

The Market That Kicked the FDA Nest was produced during the golden age of biotech, when the market churned out 269 drugs between 2000 and 2010, while weathering the VC drought and a global economic near-apocalypse. The movies may produce more blockbusters, but biotech saves lives in blockbuster numbers. Plus, I don’t think many films have cost $1 billion and taken 10 years on average to produce, while that’s biotechs’ median. The show must go on!

Biotech survived on method acting as The Market That Played with Fire, during the most recent years of this millennium. It honored its contract and performed its own stunts in battling the Extremely Loud and Incredibly Close Recession on location for three years to entertain its stakeholders, patients and fans. Even when there was talk of an Economy II: The Sequel, an exhausted biotech market never ran off to rehab, and only had one thing to say: “Makeup!”

The most biotech-applicable movie quote of the year came from Harry Potter, who said “When have any of our plans ever worked? We plan, we get there, all hell breaks loose!” How many times have you heard that in the clinical trial lab?

Roche Inc. is involved in a sequel of its own – Final Destination II, in reprising its role as the Lord Voldemort of unwelcome M&As, this time bent on controlling the Mid-Cap Earth of biotech. This time around, the role of Genentech Inc. is being played by Illumina Inc., which is staging a defiant Footloose reprise that worked so well for Genentech in resisting Roche’s hostile takeover until they relented and upped the box office take to $95 per stock ticket.

Lights! Camera! Action! Or in this case, Innovation! Capital! Research!

The nominees are:

Mission Impossible: Biosimilars Protocol – An idealist gets in over his head with lobbyists, regulators, pols and black marketeers in a quest to . . .

My Week Decade with Marilyn Margaret ‑ The recollections of an ingénue drug candidate that sought self-validation from the approval of others, while navigating the dreaded Hamburg maze, rife with complete response letters, red tape quicksand, legal maelstroms . . .

Obesity Market & the Deathly FDA Hallows: Parts I, II & III – A disaster movie with tear-jerker elements, this is the tragic story of lorcaserin, Qnexa and Contrave, lured by the bright lights of an inestimable, but weighty . . .

The Help – A feel-good, coming-of-age tale about the combination diagnostics market and the unlikely friendship of two disparate souls searching . . .

Moneyball – This offering is the rags-to-riches story of Pharmasset Inc., befriended by a New Money benefactor after growing up on the Street with little more than a small cap and a . . .

Bridesmaids – Runners-up will be left for dead on the HCV battleground in this epic war movie with a spectacular cast of stars battling it out to claim a winner-take-all foothold in the impending . . .

The Iron Lady – A patent-cliffhanger following the rise-and-prematurely-speculated-fall of the centenarian (and Lifetime Achievement Award recipient) War Horse pharma market, from its dubious beginnings, up to its current May-December romance with biotech as . . .

Twilight: Breaking Dawn – A sexy potboiler, starring the hottest young bodies-with-brains in biotech – DNA sequencing. These stud companies are charged with the ground-breaking task of potentially eradicating disease as we know it. And they get to take off their shirts a lot and expose their own blessed genetic buildups, as well as those in the blueprint for the human . . .

The Descendants – This fish-out-of-water fantasy tale follows the journey of biosimilars down the Yellow Brick Road to a hard-fought . . . oh, my bad, this project is still “in development Hell,” as we say in the business!

And the winner is . . .?

In the Harry Potter books, Hogwarts headmaster Albus Dumbledore reacts the opposite way to a similar conflict as he comes to care for Harry Potter in ways that are hard to square with the responsibility to the larger wizarding world which is also his duty. He speaks to Harry of wanting to “save you more pain than you had already suffered. What did I care if numbers of nameless and faceless people and creatures were slaughtered in the vague future, if in the here and now you were alive, well and happy?”

Clinical trials and their individual patients can face the same tensions. Treating patients according to the best evidence that is available now affects the evidence of the future.

One example is crossover designs, where patients in the control group have the chance to get the experimental treatment.

The scientific problem with this approach is not hard to see. If the control group is also receiving the active agent, and the active agent affects overall survival, then survival time in the control group will be lengthened by the investigational agent, and the difference between the two groups will be less pronounced.

Even where survival effects are strong enough to be visible at interim analyses, crossover effects will affect the final survival benefit. And that’s not just an academic concern. Taking crossover benefits into account, the survival time for Provenge almost doubles. Other trials seem to have missed their endpoints altogether due to crossover effects.

I’m not here to defend sky-high drug prices. As my colleague Mari Serebrov has movingly written about on this blog post, a cure that no one can afford is no cure at all. And I rather suspect that even after you take the high price of drug discovery into account, the profit margins on a number of drugs would raise eyebrows.

But just as we can’t lose sight of the needs of the individual patient of today, we need to remember that unless the numbers add up – unless companies can survive, unless trials are set up to be able to demonstrate benefits of the drugs they test – we can also end up doing a disservice to the patients of tomorrow.

In the newthink of the FDA, quality of life (QOL) is one of those doubleplusungood phrases that a biotech dare not utter – unless it has conducted a doubleplushuge, FDA-approved, randomized, controlled, double-blind pivotal study, including doubleplusvulnerable populations and diverse subpopulations, to demonstrate a statisticwise improvement in the primary endpoint of QOL as measured by patient-reported outcomes on the U.S. Standardized Scale of Life Quality Factors. QOL, after all, is an indication – just like cancer or rheumatoid arthritis.

Once the data are in, the FDA would convene an advisory committee of unconflicted goodthinkers with a bellyfeel for QOL issues. This Good Life Advisory Committee (GLAC) would be asked to define QOL and weigh the good and the ungood of whether the study data support an improved QOL indication. For instance, was the follow-up period long enough to establish longwise improvement? Did the trial include patients with comorbidities such as unhappiness, drug ungood use or alcohol doubleplususe?

Once past the GLAC, the bigwise challenge for drugmakers would come after the FDA approves the indication. That’s when BB will doubleplusstart watching, using its Sentinel Initiative and FDA Adverse Event Reporting System to trend ungood QOL events such as unexplained frowning, occasional bouts of sadness, tearing of the eyes, flashes of frustration, weight gains, unplanned pregnancies, job losses, relationship problems, etc.

But since the FDA is unlikely to approve a drug for QOL, drugmakers need to speedwise forget their oldthink and become goodthinkful FDA newspeakers.

On Business

“Biotech is all about picking the exception. Granting access to capital to everyone doesn’t strike me as the right idea.”

‑ Bob More, general partner with Frazier Healthcare Ventures, taking an optimistic view on capital constraints. Private biotechs continued to struggle in 2011, raising about as much money as in 2010.

"I think we're going to see a regression to quality."

‑ Jim Healy, general partner at Sofinnova Ventures, on how the venture contraction will mean that only the highest quality companies get funded. Several venture groups pulled out of biotech investing during 2011.

“The take-home message is that it’s easy to build a $25 million company with $100 million cash.”

‑ Tillman Gerngross, CEO of Adimab LLC, on the trend of sliding valuations post-initial public offering. Although a handful of biotechs went public in 2011, the window did not open as wide as some had hoped.

"You can't save your way to success in this business."

‑ Marina Biotech Inc.'s CEO Michael French on the tough financial choices small biotechs must make, such as accepting harsh terms to keep a company moving forward.

“Monday, I was in Chicago, presenting at ASCO. Tuesday, I’m in California, pitching at Goldman (Sachs). And Wednesday, I’m in New York, presenting at Jefferies. How many red-eye medallion miles does it take to get one deal?”

‑ A jet-lagged biopharma CEO, taking a break at the Jefferies 2011 Global Healthcare Conference, and illustrating just how hard biotechs had to work to close financings and partnerships in 2011

On Science

“What happens when the next 10 patients you see require eight different drug combinations based on the mutations in their tumors?”

‑ Outgoing ASCO president George Sledge, on the exponential increases in complexity required to tackle “chaotic” tumors with high mutational load. Personalization of medicine continued to be a theme at ASCO and AACR in 2011.

"You do have to be somewhat of a Talmudic scholar to prescribe this drug."

‑ Lawrence Friedman, member of the FDA Antiviral Drugs Advisory Committee, referring to the regimen for Merck & Co. Inc.'s hepatitis C candidate boceprevir. His comments illustrate the difficulties of putting more personalized treatment regimens into practice.

"The fact that it's inefficient doesn't mean it hasn't made great contributions."

‑ John Mendelsohn, president of the M.D. Anderson Cancer Center, on the National Cancer Institute-sponsored collaborative clinical trials program

“It disturbs me that people are willing to accept this: treating the symptoms and allowing the disease to progress.”

‑ Jerry Colca, president and chief scientific officer at Metabolic Solutions Development Co., on new diabetes drugs

“For every target, almost every company has an inhibitor against it. Medically, as well as economically, we truly need something to get beyond that."

‑ Chiang Li, CEO of Boston Biomedical Inc.

General Wisdom

"A lot of innovation is incremental, not breakthrough."

‑ Glen Giovannetti, global biotechnology leader at Ernst & Young

“I realize it’s absurd to talk about 10Xs or even 5Xs these days.”

‑ Roger Longman, CEO of Real Endpoints LLC

“A combination of good science, good collaborations, good timing and some good luck.”

‑ Mace Rothenberg, Pfizer Inc.’s senior vice president of clinical development and medical affairs in the Oncology Business Unit, on the secrets to the success of lung cancer drug Xalkori (crizotinib)

"You can only set yourself on fire once."

‑ Oleg Nodelman, partner at Biotechnology Value Fund, referring to how pharma stocks tend to jump when they severely cut R&D budgets

"Clearly, there are easier and less insane ways to make a living."

‑ Jim Greenwood, BIO president and CEO, at the BIO 2011 keynote luncheon

The past year brought the biotech sector a mixed bag of news. Some of it was positive – for instance, the FDA picked up its drug approval pace in 2011 and, in some cases, even surprised the most hardened biotech investors by granting approval of some drugs a month or two before their PDUFA dates – while other headlines hailed discouraging trends such as the failure of Prospect Ventures to close its latest round, confirming predictions of a venture capital contraction.

As we get ready to head into 2012 (and possibly an apocalyptic count-down, if those Mayans are to be believed), let’s take a look back at some of the highs and lows of the biotech industry in 2011.

‘Me-First’ Instead of ‘Me-Too’

Biotech execs always talk about tackling unmet medical needs. So it was exciting to see in 2011 the flurry of breakthrough drugs hitting the market. An informal BioWorld poll tagged Seattle Genetics Inc.’s lymphoma drug Adcetris (brentuximab vedotin), the first approved antibody-drug conjugate, as the biggest drug approval of the year, tied with HCV game-changers Incivek (telaprevir) from Vertex Pharmaceuticals Inc. and Victrelis (boceprevir) from Merck & Co. Inc. But other notable approvals included Human Genome Sciences Inc.’s Benlysta (belimumab), the first lupus drug approved in 50-plus years, and Yervoy (ipilimumab) from Bristol-Myers Squibb Co. and Zelboraf (vemurafenib) from Roche AG and Daiichi Sankyo Co. Ltd. as the first two drugs approved for melanoma that actually improved overall survival in clinical testing. And, late in the year, Incyte Corp. scored a win with Jakafi (ruxolitinib), the first approved JAK inhibitor and the first drug for myelofibrosis.

Let’s all hope that trend of “firsts” continues in 2012.

A ‘Nobel’ Death

In a bit of irony (in an Alanis Morissette kind of way), the Nobel committee awarded one-half of the 2011 Nobel prize in physiology or medicine to Ralph Steinman, unaware that the Rockefeller University professor had died of pancreatic cancer three days earlier. Posthumous Nobels are unusual but, after brief debate, the committee wisely decided to allow Steinman to remain a Nobelist. And I’m glad. He certainly earned the title for his discovery of the dendritic cell and its role in adaptive immunity. Plus, according to BioWorld’s science editor, Anette Breindl, who heard Steinman speak in 2007, he was a pretty nice guy.

Best Bang for the Buck?

The biggest M&A deal in 2011 was easily Sanofi SA’s $20-billion-plus-contingent value rights buyout of Genzyme Corp., which followed nine months of often less-than-friendly negotiations. But it wasn’t the best deal for biotech investors. Genzyme shareholders already have lost out on the $1 CVR connected to manufacturing capacity for enzyme replacement therapies Cerezyme and Fabrazyme. Whether they will be able to earn the remaining $13 linked to multiple sclerosis drug Lemtrada (alemtuzumab) is up for debate, and, for the most part, analysts are not optimistic.

If I were to choose, I’d say that Daiichi Sankyo Co. Ltd.’s bid for Plexxikon Inc. and Shire plc’s buyout of Advanced BioHealing Inc. were far more successful M&A deals. Daiichi’s hefty $935 million payment for Plexxikon – a move validated when Zelboraf gained approval in August – came despite only getting U.S. co-promotion rights to the melanoma drug under Plexxikon’s existing partnership with Roche AG. The Shire/ABH deal, meanwhile, showcased the kind of investor returns rarely seen these days. The big pharma firm shelled out $750 million for ABH, a whopping 15x return for ABH’s largest shareholder.

‘Weighed’ Down by Safety

Despite health experts clamoring for new ways to treat the so-called obesity epidemic, drugs aimed at helping people lose weight have not had an easy time of it at the FDA. Industry observers had expected 2011 to usher in not one, but three obesity therapies; instead, all three were rejected by the FDA. Orexigen Inc.’s Contrave got stalled on cardiovascular concerns, while Vivus Inc.’s Qnexa raised worries of birth defects related to one of its generic components and Arena Pharmaceuticals Inc.’s Lorquess bumped up against carcinogenicity concerns. Contrave is set to start a large cardiovascular outcomes study, which would delay its approval until 2014. But Qnexa and Lorquess could have a shot at getting approved in 2012. That’s assuming that no additional safety issues crop up. Given the track record in the obesity space, that’s definitely no guarantee.

The Rough Side of Town

While 2011 had its much-lauded drug approvals (as noted above), the year was not without its disappointments. Two promising areas of research suffered blows – Roche pulled out of the RNAi space, dumping a high-dollar collaboration with RNAi powerhouse Alnylam Inc., while Geron Inc. abandoned its position as embryonic stem cell pioneer to focus on a less-risky cancer drug. But the biggest disappointment of the year – as chosen by 41 percent of respondents to a BioWorld poll – was the slow sales of Dendreon Corp.’s prostate cancer vaccine Provenge (sipuleucel-T). Sales fell way below estimates, and, over the course of the year, Dendreon’s shares have lost about 80 percent of their value. The Seattle-based company has since retrenched and is hoping European approval, now pending, will help accelerate revenue growth. We’ll be watching in 2012.

And the Strange Bedfellows Award Goes to . . .

Probably one of the most bizarre deals ever in biotech was 2011’s short-lived merger agreement between Allos Therapeutics Inc. and AMAG Pharmaceuticals Inc. Having in common only commercially underperforming products – Allos’ Folotyn (pralatrexate) for peripheral T-cell lymphoma and AMAG's iron deficiency drug Feraheme (ferumoxytol) – execs from both firms tried hard to convince investors and analysts of the logic in combining the companies by pointing out a handful of “cost synergies.” But the merger was met with opposition from the get-go and even prompted hedge fund MSMB Capital Management to make an unsolicited bid for AMAG. Unsurprisingly, the deal was voted down by AMAG shareholders. Seriously, what were they thinking?

Well, that’s my list of headline-grabbing biotech news in 2011. But it’s hard to remember a whole year, and I’m sure I’ve forgotten something. What do you think were the biggest events in biotech in 2011?