Is The FDA Shooting Down ‘Me-Too’ Drugs?
8 CommentsBy Ed Silverman // July 29th, 2008 // 3:20 pm
The agency did a curious thing this week - a ‘not approvable’ letter was issued to Vanda Pharmaceuticals for a schizophrenia drug. The move stunned investors, who sent the drugmaker’s stock down 73 percent yesterday. But the FDA decision may hold much wider implications for the entire industry - a greater emphasis, perhaps, on comparitive effectiveness.
By way of background, Vanda paid Novartis $500,000 for iloperidone, which was intended for psychiatric conditions, in hopes it could be used to treat symptoms of schizophrenia. But while the drug was more effective than a placebo and had similar results as Pfizer’s Geodon, the agency expressed concern about its effectiveness when compared with Johnson & Johnson’s Risperdal and the
FDA recommended additional studies should compare iloperidone to Risperdal and Lilly’s Zyprexa.
“This came as a shock to us, since we had actually expected a relatively clean approvable letter, and it further indicates the continuing hurdle-raising at the FDA,” Corey Davis, an analyst at Natixis Bleichroeder, wrote in an investor note, according to The Washington Post. “Clearly, drugs that aren’t really novel or more than incrementally positive are going to face progressively higher hurdles for approval.”
In other words, the me-too phenomenon may be a thing of the past - and not just because the labs are having a harder time developing one.
Nathan
Talk about limiting competition. You think brand name drugs are expensive today? Just wait another 5-8 years. We’ll be wishing for 2008 prices.
But I guess drug pricing isn’t what the FDA is concerned about.
John
FDA does not have a statutory mandate (or any regulatory authority) pertaining to drug prices. But it is high time that the agency, like those in other countries, take greater account of how a “new” molecule stacks up against previously approved drugs. Drugs offering little to no clinical advantages over existing drugs, but which have more serious side effects, have long been deemed not approvable by the FDA. It’s about time the agency took the small additional step of nixing drugs that have an unknown potential for serious side effects (think Vioxx) and yet offer no demonstrable clinical advantage. The burden should be on the company sponsoring the new drug to prove that possible clinical advantages are real and outweigh unknown risks. (If anyone wants to hire me, contact me at jensign@yahoo.com!)
Dan
The Potential Fallacies Associated With Me-Too Medications
“But corruption is neither need based nor greed based. It’s simply opportunity based.” —–Billy Tauzin, president and C.E.O. of PhRMA, the pharmaceutical industry’s most powerful lobbying group, as Mr. Tauzin stated in Boston recently.
It has been said by others that the pharmaceutical industry should not have government regulation or interference from our government at all because that would drastically limit if not eliminate innovation as well as our health care choices and options, both from the perspective of the doctor and the patient, so the public has been told often by others. Also what has been stated by this industry that their internal controls prevent wrongdoing? So, according to some, the public’s health would be limited and possibly harmed without the copious innovation of this industry. As with other issues we face as citizens, this is another attempt by these others to apparently install fabricated fear in our minds- void of any proof or reason, and is a fallacy.
As it has turned out, the pharmaceutical industry’s lack of innovation in particular has happened and they have appeared to do this on their own, overall, those innovators and lifesavers.
Over the past several years, those few meds created and FDA approved with true therapeutic advantages happened by discovery with government involvement in over half of these meds with clear clinical advantages for certain patients. Conversely, of the new chemical entities approved lately and developed by drug companies, over 50 percent of these have microscopic therapeutic advantage for patients, so I understand upon information and belief. This inefficient drug development by the pharmaceutical industry has created what is now the dominant development strategy of drug companies, and this strategy is known as the intentional development of what are phrased, ‘me too’ drugs.
These drugs essentially are small molecular variations of the original molecule in a particular class of medications. In other words, they tweak the original molecule in order to obtain patent rights for their now new drug project. This me too objective of drug companies now accounts, I believe, for about 80 percent of the research budgets of drug companies. And because the FDA only requires a potential med to be superior to a placebo in their mandatory clinical trials, usually these me too meds are approved- regardless of their necessity for others, or the need for such drugs.
And me too drugs are selected by the drug company for their potential blockbuster status as well as the speculated growth of a particular market, which means making over 1 billion dollars a year on such a drug, at least. For example, statin drugs, for high cholesterol patients, is a multi- billion dollar market. As a result, there are several statin meds now available for use by doctors to prescribe to their patients. Yet, arguably, me too drugs are all essentially very similar in regards to safety, efficacy, and cost, regardless of the class referred to so often saturated with me too meds, with few exceptions. The differences overall are minor once again with most me too drugs, overall. As aggressive marketers, the makers of these meds are suspected of doing a bit of publication planning, it is suspected, to falsely claim superiority of their newly approved me too drug over all the other drugs in a particular class both during and after the creation of these me too meds. Also, other classes of meds with several me too drugs may include SSRI anti-depressant drugs, as well as those meds for hypertension. There may be a dozen drugs in a particular class of medications that are all essentially the same in regards to their treatment abilities for patients with such disease states that they treat.
Now, there may be cases where a patient tolerates one drug in a class over another for unknown reasons, so in these few cases, some me too drugs occasionally are beneficial for patients for some reason or another, but should absolutely not be a primary objective of the drug companies to create them as often as they do. Instead, true innovation and discovery should be the focus of pharmaceutical companies, and it does not appear to be the focus of the pharmaceutical industry, presently. It appears that, thanks to the Bayh-Dole Act of 1980, they license molecules from those in the academic world, and then proceed with development of another’s creation they claim as their own.
Further vexing is that competition in the pharmaceutical industry amazingly does not and has not been of any financial benefit for the consumer, as competition normally does create. This fact is greatly demonstrated with other industries and is the apex of business operations. This pharmaceutical industry model is an exception, and the reason for this remains an unknown, as far as the etiology of being deprived of this costly environment of drug spending, yet it can be speculated that the me too drug makers claim uniqueness of their me too drug, which is rather deceptive.
This progressive marketing paradigm of the pharmaceutical industry, such as the creation of me too meds solely for their own profit, clearly illustrates their focus on these issues over true research and science, so it seems. Innovation, along with ethics, use to define this pharmaceutical industry. Sadly, it seems this is not the case today, which ultimately and potentially deprives potential treatment methods potentially for the public health if the objectives were focused on their true purpose. Yet hopefully, such historical qualities of drug companies will return some time, in time.
“Most people are other people. Their thoughts are someone else’s opinions, their lives a mimicry, their passions a quotation.” — Oscar Wilde
Dan Abshear
Author’s note: What has been written was based on information and belief.
Salmon
I know no more than what’s available in your post. However just from reading the post it appears that
In one study efficacy was shown relative to placebo and was comparable to ziprasidone (not a very effective drug).
In the second study it’s less efficatious than risperidone. No details are given, however this may mean that it wasn’t efficatious.
So it looks like it may not have meet the regulatory standards efficacy, i.e. two adequate and well controlled studies. This would be the obvious reason that another efficacy study is requested.
The other thing is nothing is said about safety, although companies never do.
According to VANDA’s website “Our CEO, Mihael Polymeropoulos, MD, founded Vanda in 2003. Previously, he founded and ran the Novartis global Pharmacogenetics department, one of the industry leaders.”
Iloperidone was developed by Novartis and after the phase III trials were completed they dropped the compound and didn’t even try to submit it to the FDA. If Novartis spent hundreds of millions and didn’t even think it was worth trying. Why would a pharmacogeneticist (who I doubt has development and regulatory experience) think he could get the same drug past the FDA.
Iloperidone and bifeprunox, the drug from Wyeth that you cross reference from last year’s post, as well as ziprasidone and risperidone are all structurally similar but with some major differences. So is iloperidone more like risperidone in terms of efficacy and side effects or more like ziprasidone?
Comparison to olanzapine makes sense as it’s a different structural class, however it may also make Iloperidone look better than it is if it makes the focus on side effects be on metabolic effects rather on other side effects that might be more problematic with iloperidone.
Salmon
Bob Freeman
Nathan’s point is valid: the price competition among patented products eliminates monopoly profits. Consumers’ surplus increases and producers’ surplus decreases. The economic losses to the first-to-market patent-holder is greater than that from patent expiry.
That aside, marginal innovations that are heavily promoted take the place of generics that are not promoted; hence, the need for evidenced-based medicine and counter-detailing. Their development also has an opportunity cost associated with the failure to develop more innovative NCEs.
Atlex
Bob,
There is a definite role for marginal innovation if one accepts the fact that while two drugs form the same class may work equally, there is not 100% overlap in the patients that they work in. In other words, Drug A may work in 60% of patients and Drug B may work in 60% of patients. But they may not work in the exact same 60%. Perhaps, together than can help 80% or 90% of patients. My concern is that poorly delivered comparative effectiveness would not make this differentiation–I think the term is heterogeneity of effect.
Atlex
Bob Freeman
Atlex, I agree. Some of the criticism results from the way clinical trails are designed; viz., to show equal efficacy with an active control. It is after approval that we learn about comparative advantages in patient sub-groups. Part of the dilemma is how to satisfy the requirements of the FDA to gain approval successfully vs. the marketplace. Many times the initial arguement has to be made on side effect differences rather than both efficacy/safety.
Meg
Why doesn’t the FDA get rid of olanzapine, the number one killer atypical antipsychotic - except for those few individuals who have tried everything else, do a real review of the metabolic side effects of this new drug, and if it is safer and shows efficacy, let it come to the table?