The Big Red Biotech Blog

Avastin Decision Signal for More Cost-effectiveness Measures by FDA?

Here's a couple interesting commentaries from Seeking Alpha and The Economist -- both having to do with issue of the high cost of drugs (particularly cancer treatments) and the future regulatory role in not only evaluating the science behind them but their cost-effectiveness too.

 Both pieces use the FDA's recent decision that Avastin does not usually work with breast cancer and a lightning rod for the discussion.  The Seeking Alpha piece predicts that the FDA will become more like its EMA counterpart and will not only make decisions on a drug's suitability on safety and efficacy grounds (as it does now) but will increasingly weigh its cost-effectiveness.  The argument is that it will become even harder to get FDA approval and that bodes poorly for the financial health ofthe pharma sector.

The Economist is less predictive in what may happen but notes that Americans spent $125 billion on cancer treatments in 2010 and are proejcted to spend $207 billion by 2020 (according to Medco). Thus, they predict that the FDA will have to engage in a serious discussion soon about "how much society should pay for the extension of life."  As do we all.

Posted by Bruce Lehr July 1st 2011.

 

FDA Sets Review Date on SGN-35 ADC

Seattle Genetics has its review date with the FDA set for July 14th to get an Advisory Committee decision on its antibody drug conjugate (ADC) brentuximab vedotin (SGN-35).  BLA's for the drug's use in the treatment of Hodgkin's and anaplastic large cell lymphoma will both be reviewed in back to back sessions.

SGN-35 remains on pace to be the first ADC approved.  And if the committe recommendation is positive as widely expected, Seattle Genetics will be really have something to celebrate (besides Bastille Day) as it moves to storm the market.

 

Posted by Bruce Lehr June 16th 2011.

Phase II Clinical Trial Failures Are Rising

If at first you don't succeed, you stop the trial in phase II -- apparently.  Phase II failures are on the rise with only an 18% success rate in 2008-2010 versus 28% seen in 2006-2007.

Phase II Clinical Trial Failures Are Rising // Pharmalot.

A recent report published in Nature Reviews Drug Discovery examined the fate of 108 phase II development failures between 2008 and 2010.  The results showed:

• 87 of 108 reported a reason for the ceased phase II project
• 44 of 87 stopped due to inadequate efficacy
• 25 of 87 stopped due to "strategic reasons" (we shall return)
• 17 of 87 stopped due to safety concerns
• 21 reported no reason

The study concluded that "strategic reasons" was likely code for inadequate differentiation from more advanced drugs on the market.  This likely occurs as too many companies are chasing too few of the same targets.  Similarly, it is suspected that the 21 with "no reason" reported also represents instances of too little differentiation from more clinically advanced products as 17 of the 21 were with validated targets.

The authors also believe that recent M&A activity, subsequent "rationalization" of the pipeline and the need to "manage R&D costs" further accelerated the phase II plug pulls. Perhaps optimistically, the authors say the trend toward more research with rare diseases (novel targets) and greater emphasis on patient stratification (companion diagnostics anyone?) will help slow this phase II decline. Also, business models that emphasize external partnering and formation of consortia to lay off risk will be beneficial too.

Posted by Bruce Lehr May 11th 2011.

FTC’s Leibowitz Says Rising Generic Drug Deals Hurt Consumers

As posted here last week, the FTC's Chairman Jon Leibowitz is up in arms over an increase in so-called pay for delay deals between innovator drug companies and generic competitors.

PharmaGossip: FTC’s Leibowitz Says Rising Generic Drug Deals Hurt Consumers - Bloomberg.

Leibowitz says the number of deals increased 63% (from 19 to 31) and involved 22 products with sales of more then $9.3 billion.  He said the deals " are outrageous and they harm consumers. Either the courts or Congress needs to stop them."  The FTC has long contended the deals are anticompetitive and violate antitrust law.  Leibowitz aslo says the deals add $3.5 billion to consumer's drug costs.

Lobbyists for the drug companies say the deals cut legal costs and avoid long court battles.  In some cases, the settlement may avoid years of patent litigation and bring a generic drug to marker sooner. The deals don't prevent competition beyond a patent's life says a spokesman for the Generic Pharmaceutical Association (GPA).

"The FTC is continuing to perpetuate the myth that pro-competitive, pro-consumer patent settlements are harmful to consumers,"  said David Belian, a GPA spokesman.

 

 

 

 

Posted by Bruce Lehr May 10th 2011.

User Fees Proposed by FDA for Biosimilars

In today's Federal Register, the FDA proposed a user-fee program to support the review of biosimilars and interchangeable biological products applications. In its initial inception, it will somewhat mirror the Prescription Drug User Fee Act (PDUFA) fee program but will not exactly match it.

PharmTech Talk » User Fees: Another Step in the US Pathway for Biosimilars.

The FDA says that is wants to emphasize help in the early stages of the biosimilar development cycle and do so in a way that will not drain resources from the review of innovator products. Under the proposal, for an application in the premarket phase, there would be a biosimilar product development fee paid on submission of the application and annually thereafter -- on the order of $150,000.  A marketing application fee would be equal to the PDUFA original new drug fee less the sum of payments from the development fees above.

Once the product reached market, there would be annual establishment and product fees equal to the respective PDUFA fees.  This total fee structure would be exepcted to stay in place for the first five years of the program -- and then may be adjusted as necessary.  The FDA expects to be issuing guidelines for the entire biosimilars licensing process later this year.  At least with the fee proposal, we're once step closer to activating a biosimilars regulatory pathway. See Fierce Biotech and Pharmalot.

 

 

Posted by Bruce Lehr May 10th 2011.

 

 

Comparative Effectiveness Dissected and Studied

Comparative Effectiveness is defined as the "generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat and monitor a clinical condition or to improve the delivery of care".  It's a hot topic now that goverments worldwide are trying to control rising health care costs.

A recent study was conducted by Goldberg and colleagues at Brigham and Women's Hospital and Harvard University that examined the frequency of comparative effectiveness data being available at the time of market authorization by the FDA for NMEs between 2000 and 2010. The following results were reported:

• 51% (100/197) of approved NMEs had comparative efficacy data at time of authorization
• When orphan drugs (n=37) and drugs without alternatives (n=17) were removed, the percentage rose to 70% (100/143)
• The range varied from only 50% with comparative data in 2008 to 92% in 2010
• NMEs that received priority review were much less likely to have comparative data

Interestingly, and not particularly surprisingly, cancer treatments had comparative data available only 35% of the time.  I suspect -- though didn't have data to review -- that cancer also gets higher level of priority review. 

The researchers concluded, the "strategies are needed to enhance the accessibility of, and ultimately the use of, this information, particularly in the early marketing experience, when comparative effectiveness data from other sources are scarce or non-existent."  See PharmaGossip.

As further segue on this topic, the Pharmalot blog presents an additonal study from the National Pharmaceutical Council.  This study polled 111 people from federal agencies, consumer and trade groups, insurers and academics regarding various aspects of comparative effectiveness research (CER). The results:

• 55 percent of respondents were "very familiar" with CER
• 68 percent believe it will take less than 3 years to establish rresearch standards for CER
• 85 percent felt CER had little to no impact on improvement of health care decision making in the past year
• 30 percent believed it would lead to moderate improvements in the next year
• 78 percent believe the Agency for Healthcare Research and Quality (AHRQ) will set standards
• 64 percent the NIH will set standards
• Most believe AHRQ and NIH will set research priorities though 63 percent believe that will fall to the Patient-Centered Outcomes Research Institute (PCORI)
• 85 percent believe academia will do the work and 63 percent believe it will be pharma

There you have it.  Bascially, you have a new concept being introduced with the healthcare reform bill.  Most believe it will take several years to gain traction.  And most believe academia will actually generate the research -- although one might ask where that funding will derive from for head to head clinical studies?

Posted by Bruce Lehr May 4th 2011.

Lucentis vs Avastin - Poster Child for Comparative Effectiveness

The results are in for a trial known as CATT that compares Lucentis and Avastin in the treatment of macular degeneration.  Drum roll please!  To the surprise of very few, Avastin appears to be just as effective in treating the disorder (based on vision testing) as the much more costly Lucentis.  Another year of follow up may show something -- but don't hold your breath.

The NEJM published the results and editorialized:

Health care providers and payers worldwide will now have to justify the cost of using ranibizumab [Lucentis].  Regulators in certain countries will be forced to reconsider policies that make it illegal to use drugs off-label, particularly when so many of their citizens cannot afford ranibizumab.

Let's see, it's $23,400 per Lucentis patient per year versus $595 per Avastin patient per year with same level of improvement in vision.  Multiply difference by 250,000 patients treated annually in US and you have a cool $5.7 billion -- yikes!   Hmmmm - we might save $5.7 billion. Which one should we pick?  I wonder.  See In Vivo blog, Examiner.com and In the Pipeline.

Lucentis is the first Poster Child.

Posted by Bruce Lehr May 4th 2011.

Comparative Effectiveness Day in the Blogosphere

Today we have a lot of chatter about Comparative Effectiveness data (or lack thereof) in blogland.  This seems to be one of the hottest buzz topics in healthcare reform and even in design of new clinical trials.  It seems especially pertinent that drug makers are being asked to show that their shiny new drug is better than that old standby drug when it comes to Medicaid (or other government payers) or other third party payers shelling out big bucks for the newbie drug on the block - especially in this time of healthcare reform and cost reductions pressure. 

As we shall see in the following posts, several studies have pointed out the current flaws with lack of available comparative effectiveness data and well as its actual impact this year on healthcare policy decisions.  We will also see the first "poster-child" comparative effectiveness study results/conclusions from the Roche/Genetech versus itself with Lucentis vs Avastin results for the treatment of macular degeneration.  It seems the [vastly] more expensive Lucentis performs no better than the cheaper Avastin.  Oops. : (

As Chicago might sing "This is only the beginning"

 

 

Posted by Bruce Lehr May 3rd 2011.

 

FDA 'Strategic Priorities 2011-2015'

This is straight out of the FDA Transparency blog this morning announcing the agency's release of its strategy for the FDA over the next 4 1/2 years as outlined by Commissioner Hamburg.

Titled “Strategic Priorities 2011 – 2015: Responding to the Public Health Challenges of the 21st Century,” the 50-page document provides a vision of the FDA that includes:

a modernized field of regulatory science that draws on innovations in science and technology to help ensure the safety and effectiveness of medical products throughout their life cycles

an integrated global food safety system focused on prevention and improved nutrition

expanded efforts to meet the needs of special populations.

Senior staff from the FDA’s seven product and research centers and two major offices contributed to the document. A Federal Register notice that invited public input in October 2010 generated more than 200 comments that were considered for the final document.

The field of regulatory science and innovation is among five cross-cutting areas that will serve as strategic priorities at the agency during the next five years.

The FDA must have the capacity to effectively oversee the translation of breakthrough discoveries in science into innovative, safe, and effective products and life-saving therapies. This document sets forth our priorities for achieving that goal.

Thank you,

Margaret A. Hamburg, M.D.
Commissioner of Food and Drugs

 

 

 

 

Posted by Bruce Lehr April 20th 2011.

Safety First: Why I Love Drug Regulation?

Here's a good post by Stewart Lyman in Xconomy.  It points out the folly of blaming primarily (or solely) the FDA for the pharmaceutical industry's lack of recent drug approval success and innovation. It also reminds us that the FDA's chief responsibility is to ensure safety and efficacy. This is good counterpoint given the prevailing winds that sometimes like to blame the FDA (regulation) for lack of innovation (see Viehbacher and Lechleiter comments at PhRMA yesterday as an example).

Why Do I Love Drug Regulation? Simple: It Keeps Us Safe.

I recommend that you give this a read and reflect on a history of bad company behavior's in the past and not so distant past that led to the foundation of the FDA and its regulatory role in ensuring safety and efficacy. There is a good reason that it exists -- to protect you and me from charlatans and bad science.  KInd of reminds me of people who rail against Unions -- but there is a very legitimate set of reasons why they came into existence - of course institutions do need to continue to evolve and the FDA is no different in that respect.   

Lyman finishes his article:

The problem facing the pharma and biotech industry isn't excessive regulation; it's a lack of inducements in the midst of a drought (ed note: self-inflicted I might add) of innovation.  Let's create significant new incentives that will reward companies for generating new drugs to combat the problem.  Among the possibilities are significant tax breaks, longer patents, and guaranteed pricing tied to effectiveness.

I tend to back tax incentives and particularly pricing premiums for drugs that actually work and provide real patient benefit. I'm much less enthused about extended patent lives. But that's me.

Posted by Bruce Lehr April 15th 2011.

Mylan Sues FDA in Race for Lipitor

I'm sure this will become business as usual as each new blockbuster hits its patent expiration date and generic competitors vie to be first to market and gain 180 day exclusivity in the process.

In this case, Mylan is suing to force the FDA to block Ranbaxy's application to sell generic Lipitor first and to deny Ranbaxy 180 day exclusivity in the process. Mylan says Ranbaxy should be denied as the FDA accused it of submitting false data in previous drug applications to the agency in 2009. 

Ranbaxy wants to go to market in November.  Mylan is also seeking approval of its generic version of Lipitor and wants to go to market in June when certain Lipitor patents expire on June 28th. Mylan has asked the court to force the FDA's hand in making a decision - NOW.

The FDA says it is still considering both applications and won't make any exclusivity decisions until it makes (or gets ready to make) and approval -- and that may or may not come prior to June 28th.  Mylan says this uncertainty around Ranbaxy will cost it market share and is revising its share estimates down from 40% to 20%. 

Meanwhile, Watson Pharmaceuticals in a deal with Pfizer will be launching the only "authorized generic" form of Lipitor (what marketing!) and is also targetting a November launch.  I think we can all look forward to more of the same with other blockbuster "generics" in the future. See the WSJ.

 

 

 

 

 

 

Posted by Bruce Lehr April 7th 2011.

mAb Development and FDA-Approval Facts

Deloitte Recap recently analyzed the 29 mAb approvals that have thus far passed the FDA. These drugs generated an aggregate $24 B in revenues in 2009.  In looking at the length of time the mAbs were in development, Deloitte found that their mean time to market was 7.6 years - but this time frame is getting longer.  For the period, 1994-2003, the mean time was 6.7 years and that has increased to 8.3 years for the time span 2004-2011. This could possibly be due to the increased complexity of diseases that developers are now trying to attack - most of this time is from additional time in the clinic.

Surprisingly, and unfortunately, Deloitte also discovered that the regulatory programs geared at speeding up a drug's time through the approval process - like fast track, accelerated approval, priority review or orphan status - did not seem to help mAbs arrive any faster.  In fact, fast track status was associated with a longer mean time in development. 

In looking at the data for mAbs, particularly as compare to small molecules, Deloitte also concluded that mAbs approval rates are higher (23 percent), and given some are blockbusters to boot, we're likely to see heavy investment in mAbs for the foreseeable future.  At present, 27 key companies followed by Deloitte have 130 mAbs in their pipelines aimed at 211 indications.

Posted by Bruce Lehr April 5th 2011.

 

No Mas! - KV Capitulates on Makena Price

The FDAs announcment a couple days ago that it would not enforce exclusivity with compounders making cheaper, non-approved versions (the original versions) of KV's newly approved Makena appears to have been the final straw.  Already under fire from patients, lawmakers, physicians, third-party payers, foundations, patient advocates, pundits and the Baja Marimba Band and the Mormon Tabernacle Choir, KV decided enough was enough and rolled back its list price from $1500 to $690.  See St. Louis Biz and Pharmalot blog.

This is still quite a bit more than the compounder's $20-$30 per patient price but does represent a 55% decrease from the $1500 price point.  Said KV Chief Exec Greg Davis,

We understand the concerns that key stakeholders raised under our original pricing structure.  We also recognize the current budget challenges facing state Medicaid programs and other payers.  In conjunction with our substantial reduction in price, it is our sincere hope that all committed stakeholders will take appropriate action to provide timely access to this important FDA-approved medication.

In other words, "Please don't go to the compounders. No Mas!"

 

Posted by Bruce Lehr April 1st 2011.

 

KV Decision. Brings FDA Controversy?

The following post from Pharmalot provides an interview of two FDA watchers from the healthcare analysis firm, Prevision Policy. They have several comments on how the FDA's decision in the KV case broke with precedent. The comment that I find most interesting regards pricing.

The KV Preemie Drug & An Unusual FDA Decision // Pharmalot.

The analysts note that the FDA looks like it responded in the KV case as a direct result of KV's proposed pirce hike of treatment from aroudn $20 to $1500 per dose. The FDA is not supposed to concern itself with pricing and has no idrect jurisdiction. The analysts wonder if they aren't now on the slippery slope.  For example, why don't they get involved with Provenge's ($93 K per patient) or Yervoy's ($120 K per patient) pricing? 

I think there is a distinction to be made.  Both Provenge and Yervoy are drugs that were just developed - at considerable risk and expense by Dendreon and BMS (or its companies) respectively.  both are novel therapies for cancer. These companies did actually invest.  In the case of KV, they merely got an existing therapy licensed.  They did do some work and they do deserve a premium for that work.  The question is should it be the premium represented by a $20 to $1500 increase?  Especially, since they did not discover the drug, it was in use for decades from the compounders, and they don't even manufacture it.  And -- they are exploiting the Orphan Drug Act to gain exclusivity and the CHOSE to introduce a price that is offfensive to many in the medical community.  That's the problem - they are outpricing their perceived value with minimal investment and risk on their part.

So they got slapped.

 

 

Posted by Bruce Lehr March 31st 2011.

 

FDA in NOT Pursuit of Makena Compounders

The FDA struck a blow at KV's plan to sell Makena for $1500 a pop by saying it will NOT go after compounders who continue to make the "unapproved" versions of the drug.  That is providing the compounder is following appropriate standards, and is formulating a safe and effective product.  Since compounders have been providing this product for 50 years, many know how to produce just fine.

FDA Won’t Pursue Compounders Making KV Drug // Pharmalot.

The FDA is taking this unusual stance despite the fact that KV just went through the trouble of getting and FDA approved drug, and did so under the auspices of the Orphan Drug Act to afford itself market exclusivity.  This action by FDA effectively negates the exclusivity protection and the agency says it is doing this over a concern that the product be available to all consumers who need it

KV was counting on market exclusivity to support its price.  Now KV stock is in a nose-dive and dropped 33% today after the FDAs position was made public.  That is a very effective way to block this type of price exploitation and is a LOT quicker than waiting for the FTC to act, or the Congress to rewrite aspects of the Orphan Drug Act were it so inclined.

 

 

Posted by Bruce Lehr March 30th 2011.

KV's 'outlandish' price for prenatal drug stirs hornet's nest

KV's pricing decision on its hormone therapy, Makena, has done it now.  Most of you are undoubtedly aware that the company successfully introduced an FDA approved version of the drug earlier this month under the Orphan Drug Act.  With its FDA approval and seven years market exclusivity provided by the act, KV promptly raised the list price to $1500 per dose from the prevailing rate of $20-30 that was being delivered from in-house compounding pharmacies.  The next sound you could hear was the hornet's buzzing!

Backlash builds over KV's 'outlandish' price for prenatal drug.

KV now has members of the US Senate, the FTC, the March of Dimes, the NEJM, the American College of Obstetricians and Gynecologists (ACOG), and the American Academy of Pediatrics in hot pursuit and calling for them to roll back their "outlandish" price.  The FTC, at the Senate's request, will investigate whether the company is engaging in "potential anticompetitive conduct".  Most of the above groups have contacted KV directly to lobby it to reduce its price - even its former allies, like the March of Dimes, has expressed shock and outrage at the pricing decision.

For its part, KV seems to have figured out that it made a serious error in judgment but may not have figured out what to do about it.  It does seem to know that it will be unlikely to get past third party payers at this point and all the other anti-constituencies that it has united.  KV issued a statement in its latest 10Q filing with the SEC acknowledging the risk it now faces with its pricing.  It noted the following issues it needs to deal with for its pricing of Makena:

• Ability to maintain certain net pricing
• Degree of success in obtaining 3rd party reimbursement - including government, privae health insurers, HMOs, insurance companies, and Medicaid
• Convincing medical practitioners to prescribe
• Degree to which compounding pharmacies continue to produce unlicensed alternatives

"The success of the Company is largely dependent upon these efforts and appropriately responding to both the media and governmental concerns regarding the pricing of Makena."

As noted by several commentators, the whole circumstance appears to have been created by KV receiving Orphan status and exclusivity for a product it did not discover, didn't fund clinical trial work on, and don't even manufacture.  Then it MADE an egregious pricing decision for which it is deservedly being criticized.  However, one must question why Orphan status was even a possibility on a drug that had been around for 50 years, was previously shown to work in this application.  KV added some benefit in producing it under GMPs but certainly did NOT create any clinical value to the patient or provider along the lines of a $20 to $1500 per dose increase.  That's just plain greedy. 

This type of action I hope will be considered by the Congress in lookng at the Orphan Drug Act.  The Act has been good generally but is clearly intended as a carrot for companies to produce novel treatments for diseases/markets that would otherwise be unattractive for their revenues -- unless conferred with exclusivity.  However, it was not intended to allow a company to take an old treatment - gain approval - and then exploit a pricing position under a regulatory monopoly.  With the law written as it is, there is nothing to prevent another company from doing the same in the future.  It wouldn't surprise me if someone was working on new (old) projects right now. 

 
Posted by Bruce Lehr March 26th 2011.

EU Register Of Clinical Trials Is Launched Online

The European Medicines Agency (EMA) yesterday launched on online register for clinical trials for the first time.  The register provides public access to clinical trial information in the 27 EU member states, Iceland, Liechtenstein and Norway.  The information posted is provided by the trial sponsor and is a component of its application to conduct a trial.

PharmaGossip: EU Register Of Clinical Trials Is Launched Online Today.

The EU Clinical Trials Register increases the transparency of medical research and will make it easier for pateints to find information about clinical trials in progress in Europe. The EMA says it will continue to work to improve the register by enhancng the quality and completeness of data, and improving the search functionality.  Plans for the future include the publication of summaries of clinical trial results.

 

 

 

 

Posted by Bruce Lehr March 26th 2011.

FDA and EMA Collaborate on QbD Assessments

The FDA and the EMA have established a new pilot program to assess quality by design (QbD) aspects of new drug applications (NDAs) and marketing authorization applications (MAAs).  The program is voluntary.  Each agency will separately assess QbD elements but the agencies will then communicate on their findings. This voluntary program will only apply to new chemical entities (NCEs) and not to biologics. The pilot wil run through March 2014.

The goal of the program is to increase the harmonization between the two agencies in their assessments of new applications relative to QbD elements -- specifically looking at the CMC section.  The program originated of a concern that the ICH guidelines were not being interpreted the same from the two agencies.  The pilot hopes to address by:

• Ensuring consistent implementation of ICH guidelines for manufacturing
• Increase awareness by staff who review marketing applications and inspect facilities
• Better define reviewer and inspector interaction
• Create mechanism for EMA/FDA reviewers to share findings
• Harmonize regulatory decisions to the greatest extent possible

"To fully implement QbD, we need to further harmonize the implementation of the guidelines, work collaboratively, and provide scientific, risk-based regulatory decisions in a timely manner, " said Janet Woodcock, director of FDA's CDER.  See Benzinga.com.

 

 

 

 

Posted by Bruce Lehr March 20th 2011.

 

 

FDA Official: Another Tainted Drug Is Inevitable

The statistics are there in black and white.  In 2001, there were roughly 1200 foreign manufacturing plants for pharmaceuticals.  In 2008, there were 3500.  That's an 185% increase.  The FDA increased its inspections by 23% but that only led to a 57% decrease in the foreign plant inspection rate.

FDA Official: Another Tainted Drug Is Inevitable // Pharmalot.

What to do about it?  The FDA is touting a 4 point plan.  The plan calls for the following:

• Partnering with foreign counterparts to creat a global coalition of regulators
• Building a global data information system
• Improve intelligence gathering and focus more on risk analytics
• Tap both public and private sources - like foreign regulators

Some of this process has begun for years now according to deputy FDA commissioner John Taylor,  but the efforts need to be stepped up. In meantime, he said "another pubic health crisis like Heparin seems inevitable." Not a cheery thought.

 

 

 

Posted by Bruce Lehr March 15th 2011.

Will US get Left Behind in Making Biosimilar Rules?

The Biosimilar Blog makes the Biosimlar score:  Europe 14 US 4.

Europe has been out ahead of the US in creating guidelines and a regulatory pathway for biosimilars to reach its market.  They have guidelines in place to cover at least 36 separate marketed biopharmaceutical products and 14 products are already approved.

The US has only 4 approved "biosimilars" - being Omnitrope, Fortical, Hylenex and Glucagen.  None followed a true biosimilar regulatory pathway as there isn't one yet in the US.  The legislation has just passed and the FDA is still in the lengthy process of establishing the regulatory framework for biosimilars to be approved under the new legislation. It appears this will take a while. 

In the meantime, the only way generic recombinant proteins can get licensed is via the generic drug 505(b)(2) pathway.  And this only will be applicable if the drug in question was approved via CDER with an NDA - which normally is used only for small molecules.  Most biopharmaceuticals are approved under a BLA thorough CBER and therfore can't use 505(b)(2).

The authors worry that the US will dicker too long and be left out from being in the forefront of developing biosimilars regulations in the world stage.  Other geographies will lead the way and gain the upper hand in promulgating the regulations and gain experience working on them while the US is still drafting.

The authors plea for US constituencies to stop worrying about protecting innovators by blocking biosimilar competition and worry about creating a pathway whereby biosimilars can be approved --- like the rest of the world is doing.  They further note that there are many other ways to provide innovators with incentives to keep innovating (permanent R&D tax credit anyone?) but that blocking biosimilars shouldn't be one of them.  Let's get in the game.

Posted by Bruce Lehr March 12th 2011.

FDA to Issue Biosimilar Rules "Very Soon"

As reported in Bloomberg, the FDA's Margaret Hamburg said the agency would be issuing its guidelines for biosimilars in "the very near-term time frame."  The FDA is weighing how extensive the clinical trials should be to judge whether biosimilars work the same as the licensed reference product.  At present, since no rules for biosimilars exists, companies who wish to introduce a copy of a biologic with an expiring patent are filing BLAs.  BLAs are more time-consuming and expensive than the pathway the FDA is expected to propose for biosimilars.

The Congressional Budget Office estimates that biosimilars once approved will save in aggregate $25 B per decade for consumers.  A spokesman for Teva, a leading biosimilar company, says th enew rules are critically needed so his company can stop filing BLAs to access the US market.  Teva is known to be working on biosimilars for Amgen's Neulasta and Roche's Rituxan.

In developing its biosimilar rules, the FDA is considerng user fees to expedite the review of biosimilar applications.  These would be on the order of $1.5 M and would allow the filing company to seek FDA advice during development and result in "timely consideration" as to whether their product could be automatically substituted for the reference.

Analysts still expect only the companies with deep pockets to pursue biosimilars at first as both clinical trials and user fees are expected.  The list of companies often includes Sandoz, Teva, Hospira and Actavis as among the better funded biosimilar producers.

 

 

Posted by Bruce Lehr Feb 26th 2011.

FDA Moves to Risk-Based Approach on Process Validation

The FDA confirmed in its latest guidelines for process validation that it wants to go to a risk-based approach.  This is consistent with the direction of previoud drafts.  The biggest change - welcomed by industry generally - is the removal of any requirements to perform viral clearance and impurity removal studies under GMP conditions.  These now only need to be done under quality unit oversight.  This makes sense for companies not wanting to expose their manufacturing site to dangers durign development of these processes.

Final Process Validation Guidance Confirms FDA’s Move to Risk-Based Approach.

The new guidance is consistent with ICH Q5A and Q10 and the European CPMP/BWP/268/95.  It confirms that process validation shoudl be looked at as a lifecycle activity rather than a one-time event. The FDA says the guidance "encourages the use of modern pharmaceutical development concepts, quality risk management, and quality systems at all stages of the manufacturing process lifecycle..."

I can say that we've incorporated more and more risk-based anaylses into developing our R&D schemes and have found these exercises in proactively identifying potential hurdles and using the information in study design.  It just makes sense to be aware of risks when putting studies together (process validation or otherwise).

Posted by Bruce Lehr Feb 25th 2011.

Should FDA Hit The Brakes On Accelerated Approval?

Here's a follow up story from the Pharmalot blog to a post here yesterday on FDA scrutiny of the accelerated approval program.  Bascially, the post concludes that many approvals under the program really come with inadequate clinical trials in terms of safety and effectiveness asssessments.

Should FDA Hit The Brakes On Accelerated Approval? // Pharmalot.

However, the quandry is that if all drugs required randomized, controlled trials for all drugs -- especially oncology drugs -- the thought is that most of these would be greatly delayed in making these available to patients.  Of course if they don't work, what's the problem? It's the other side of the coin.  Big delays for drugs that do have clinical value and life-extending effects.

So where do we draw the line?  When should we accelerate availability of medicines to dying patients?  I suspect we ought to look at the bigger picture and approve based on science and not solely on compassionate grounds.  However, it is extremely naive to think that individual dying patients, their families and their advocates are going to like that answer.

Posted by Bruce Lehr Feb 9th 2011.

FDA Says Six Drug Makers Didn't Finish Follow-Ups

The WSJ reports this afternoon that the FDA said six drug makers, who received accelerated approval for their cancer treatments, did not complete follow-up studies that were promised in exchange for that approval. Among the six are Amgen, GSK and Eli Lilly. 

Richard Pazdur, head of the FDA's cancer division, said, "These confirmatory trials are as important -- if not more important -- than the initial trials leading to the accelerated approval."  Some of the companies have been delinquent for more than six years.

The FDA has the power to fine companies millions of dollars or to even withdraw approval.  My question, "Have they ever done so?"  If not, I wonder what the Company's incentive for doing the follow up studies might be? I know their disincentive. 

For example, Roche's Avastin and AZ's Iressa are two drugs that failed to show benefit in follow up studies for certain approved applications.  The result was the drugs lost their approval - a powerful disincentive to report I'd say.  To date, five drugs failed to confirm benefit in follow up studies.

Would the number have been higher if all the drugs receiving accelerated approval had met their post-market reporting requirments?  We may never know.

 

 

Posted by Bruce Lehr Feb 8th 2011.

 

 

EMA Tackles Biosimilar MAbs

This post from The BioProcess Blog gives a good overview of the recent EMA DRAFT guidelines for biosimilars - the same project FDA is currently trying to tackle in the US.  The Bioprocess blog makes it clear that they think the EMA has taken a practical approach.

EMA Tackles Biosimilar MAbs « The BioProcess Blog.

The EMA guidance makes it clear that the focus in clinical trials for biosimilar MAbs should be the demonstration of similar efficacy and safety between the biosimilar product and the reference product, not patient benefit per se, and recommends that the most sensitive patient population and clinical endpoint should be used to better identify potential product-related differences.

What's more? The ability to extrapolate “clinical efficacy and safety data to other indications of the reference mAb, not specifically studied during the biosimilar's clinical development will certainly accelerate development and reduce the overall costs of bringing these products to market.

The authors note that Europe continues to take the lead in establishing clear regulatory guidelines and requirements for biosimilars and is working diligently to allow European patients access to all types of biosimilar products. Canada will probably continue to follow the EMA’s lead so we expect a similar guidance from Health Canada soon. 

We can only hope that FDA now moves diligently to implement clear, reasonable guidelines and regulations for the development and approval of biosimilars in the US.

 

 

 

 

Posted by Bruce Lehr Feb 1st 2011.