When A ‘Me Too’ Drug Is One Too Many
20 CommentsBy Ed Silverman // February 16th, 2011 // 11:06 am
The drug development race is pockmarked with efforts to discover and market a first-in-class treatment. Of course, not everyone can be first, which means there are likely to be other meds that become available. This has become known as the ‘me too’ syndrome, in which one drugmaker after another tries to develop a med similar to a big seller and grab a piece of the business.
This approach, however, has been skewered for failing to yield needed innovations and using resources - at companies and at the FDA - that might be put to better use. So how can this be modified in a way that would realign priorities and generate better outcomes and returns for all considered?
An essay in the Journal of the American Medical Association suggests an alternative approach - require me-too meds to prove superiority over a placebo or non-inferiority to another drug, but only until a generic version is approved, write Joshua Gagne and Niteesh Choudhry of the department of nedicine, Brigham and Women’s Hospital and Harvard Medical School (here is the abstract).
And then what? They propose drugmakers seeking FDA approval must demonstrate, not just noninferiority, but superiority compared with available drugs. Superiority could be established by based on improved safety or efficacy; additional indications could be sought for other populations, such as the elderly or children, or a new indication may be pursued altogether.
Of course, they note that natural market forces may limit further development of me-too drugs and third-party payers can certainly impose higher co-payments. But this does not stem the use of public resources - namely, tax dollars spent by the FDA. The goal, they write, is not to limit competition, but raise the bar for approving “next-in-class” drugs, “which may help address the market distortions that patents for me-too drugs currently create.”
“This proposed approach is merely a modification of existing regulatory structures to help maximize the return from the societal investment on prescription drug approval,” they maintain. “If reviewing (me too) applications adds drugs to the market that are not any better than a multitude of existing products, instead those efforts should be devoted to the evaluation of other therapies that may have greater potential for making improvements in resource use, safety and efficacy.”
Your thoughts?
Analytical Scientist
Makes a lot of sense to me.
Jay
Another swipe at Pharma by an academic who has no idea about drug development. The FDA dosen’t have a category called “me too” drugs (except generics…). Companies don’t set out to develop me toos - they start with a compound that is expected to be better, faster, safer, or more convenient..and then during development reality often reveals a drug that is not that great an incremental advance or has it’s own tradeoffs. If the regs allow comparison against placebo, that what companies do. There are aleady enough hurdles to get a drug successfully approved - and provide choice and competition in the marketplace. do we really want to create one more reason Pharma will be disincentivized to develop new meds??
NJBiologist
“But this does not stem the use of public resources - namely, tax dollars spent by the FDA.”
OK, I’m curious: what proportion of the cost of a review is borne by taxpayers, and what proportion comes from user fees? How much tax money could we actually save here?
Analytical Scientist
The FDA does look at the current standard of care, and they absolutely are aware of the incremental medical value of the newly submitted drugs. It’s one thing to have a race to market with two drugs finishing 6 months-1yr apart, but it’s entirely different to have new statins or proton pump inhibitors after half a dozen are already on the market. The FDA is responsive to politics, and it’s policies swing a bit to align with the party in power. The above proposal is actually quite moderate compared to many serious proposals that have come from the Democrats in Congress.
It may all be somewhat moot, though, because even if you could get a new statin approved today with only non-inferiority to (for example) simvastatin, the payers would never give it decent reimbursement.
Nathan
Most people have a completely wrong impression of what a “me too” drug is. Drug development takes a decade or more. By the time a company has a blockbuster drug, competitors cannot just develop a “me too” drug in a year or two. Rather, the “me too” drug was already in the development pipeline long before the blockbuster drug was ever approved. Why does it work this way? Because scientists at all the major companies are reading the same literature and going to the same scientific conferences. Once a new “hot idea” comes along, all the companies jump on board and are racing to be the first to market. By strongly penalizing those that are not first to market, you are creating a toxic atmosphere where companies would have a major incentive to take “shortcuts” to be the first to market. This could actually jeopardize the safety of the ultimate product.
laptop cases
In my opinion drugs aren’t good at all ,they give you a nice and strong dependence and if you want to take them for life all you have to do is to drop them in your mouth. PS: DON’T FORGET TO TAKE THEM WITH A GLASS OF WATER.
Kay
Another thing to consider is that drugs work differently in different people. It’s not unusual for a patient to have to try several different drugs (even those in the same class) before they find one that works for them. One person’s “me too” drug is another person’s drug of last resort.
Insider
I think superiority studies just promote fraud. I have not seen a decent one that was done properly and showed superiority.THE FDA requires superiority studies to placebo for approval. If the drug has additional risk factors than the one on the market then they do not like that type of fact and may not approve the me to drug.
I don’t see the rules getting followed for the current process and adding more rules will result in more fruadulant research in my opinion whcih is getting common as it is.
Jake
Tax dollars spent by FDA? What are the million and a half dollars in user fees not covering?
If a company wants to develop a ‘me too’ drug, FDA should approve or disapprove based on the drug’s own merits and risks. A higher standard should not be applied. These products will eventually be judged when it is time to gain reimbursement.
xcelentx
Kay is right on it - different flavors really do provide opportunity for individuals to find a drug that works best for them. And consider: does this rationale, carried to its logical endpoint mean a single drug for every indication? Analytical Scientist’s point is perhaps the most critical - FDA approval is not the last hurdle, you have to get the reimbursement approvals from managed care folks or your “me too” will never leave the drugstore shelf.
Cliff Mintz
Seems to me that the authors may have ties to branded pharmaceutical entities. If the generic version of a branded product has safety and efficacy issues, it will like the innovator product, not be prescribed much. Consequently, as many have stated above, if FDA or any other regulatory agencies determine that a me-too or a new branded medication is safe and efficacious then it ought to be approved.
Stifling approval of generic drugs by requiring them to be superior or safer is a way to maintain control of the market by branded pharmaceutical manufacturers.
Rich
“This proposed approach is merely a modification of existing regulatory structures to help maximize the return from the societal investment on prescription drug approval,” - where did this concept come from? Suddenly the public needs a return of investment for the privlidge of having FDA review! Industry pays a hefty user fee to supplement review costs, and we have a very effective regulation that is supposed to give priority review to important NME’s - can’t the FDA just do it’s job and give standardreview to all the other NDAs(which are declining in number!) -
without trying to become another Health czar evaluating cost-effectiveness. As stated above, the payors, and the market will do that if a drug developer chooses not to do comparative studies….
Pharma Critic
When the first drugs in a class go generic. Once that happens, the followers should have to demonstrate superiority to justify cost. It happens in many areas of the world, but not the US. One of the big reasons we can’t control health costs!
industry insider
Kay is correct, and statins are a good example of how genetic polymorphism influence the relative likelihood of a person getting myopathy from a particular statin, as described in the linked article below. ACE inhibitors are also a good example. Early ACEI’s like captopril were difficult to tolerate due to persistent cough as a side effecrt. Later ACEI’s produced less cough, and hence better compliance.
http://www.lipidsonline.org/commentaries/al_abstract.cfm?abs_id=Abs062.
From a practical standpoint, inferiority trials will not be done unless the payoff is huge. This is because with inferential statistics, many more patients are requied in a non-inferiority trial in order to reject the null hypothesis of non equivalence than are required to reject the null hypothesis of no difference from placebo in an ordinary placebo-controlled trial. More patients means more expensive trial be several orders of magnitude.
FDA is on record as notwanting to regulate the practice of medicine. Let the marketplace sort out winners from losers.
John
With 50% of the national healthcare expenditure going to physicians and physician-managed enterprises, it never ceases to amaze me how we never see and article in JAMA or NEJM looking for savings out of that side of healthcare. Instead they seem quite obsessed with the 10% spent on drugs.
In what other part of our economy do we allow people who are paid by the number and nature of the tasks they perform a free hand to decide which tasks are necessary?
What would our military spending look like if we gave our generals a free hand to spend whatever they decided was necessary, and then set their salaries as a fraction of what they decided to spend?
industry insider
As a public service, I purchased the article online. Don’t bother. Just a commentary. No hard data. I guess a sucker is indeed born every minute.
AlChemist
‘me too’ have their place, as an example Vioxx and Celebrex- there is no way of predicting who will respond to each
Steven Grossman
My unofficial calculations:
FY 11, under the current Continuing Resolution (CR): $465M for CDER from public funds (BA appropriations) and $479 from PDUFA funds. Even were the President to be granted his FY 11 request, it would only make funding 50/50. It is widely said that PDUFA funds account for 2/3 of the cost of drug reviews, which is consistent. (by comparison, PDUFA only funds about a third of CBER and MDUFMA funds less than 15% of CDRH). Should the current cuts in FDA in the House CR bill, HR 1, the percentage of funding from user fees would increase dramatically.
For those interested in working for more resources for FDA, I suggest you check out http://www.StrengthenFDA.org. If you are interested in joining the Alliance for a Stronger FDA, please contact me at sgrossman@strengthenfda.org.
foln16
PharmCritic — you write: “It happens in many areas of the world, but not the US.” Can you please elaborate with some references about these sorts of higher approval thresholds in other countries? Many thanks!
in and out
Seems like a very good way to give the first-to-market an even bigger cash-flow protection than they already enjoy . . . not only would they be protected against patent infringement, but there would also be new, higher hurdles placed on any possible competitors trying to enter the market. Seems like a monopolist’s dream . . .