Lemtrada fails to get US FDA Approval

[Marco]

The Food and Drug Administration (FDA) "has taken the position that (Sanofi unit) Genzyme has not submitted evidence from adequate and well-controlled studies that demonstrate the benefits of Lemtrada outweigh its serious adverse effects," Sanofi said in a statement on Monday.

"FDA has also taken the position that one or more additional active comparator clinical trials of different design and execution are needed prior to the approval of Lemtrada."

[Thinkimjob]

Oh great. Which means the Australian lot won't approve it, either, and I'll be stuck with Aubagio, which is, frankly, fairly hard core so far as side effects go.

[Marco]

I completely agree with the FDA on this one. There is already litigation pending because of the Sanofi-Genzyme purchase and it should prove interesting. Unfortunately, the drug company let patients and investors down on this one.

[batman12]

It has already been approved in Australia

Think that the tga will be reviewing public funding in March but not 100%

[MSer102]

Now we get to hold on and watch as the possible scenarios play out.

Campath is already an FDA approved drug. The manufacturer chose to pull it from the market (at least in the US) so it could only be gotten as the more expensive Lemtrada. In theory Campath could be put back on the market and used off label for MS. There's already a market of people with MS waiting for it.

I don't know of another situation like this. The FDA could prevent Campath from being put back on the market as a cancer drug, but I can't think of another situation where the FDA has prevented a drug from being put back on the market because of its potential to be used off label for a particular purpose. And I don't know of another situation where the FDA has varied from common practice and prevented an approved drug from being used off label. There might be one but I've never heard of it.

The manufacturer said they plan to appeal. I can't imagine what their basis for an appeal would be. The FDA looked at the drug application pretty closely, so it's not likely that they missed anything. I think it's what they didn't miss that doomed the application. Knowingly submitting faulty data is probably unforgivable.

Another clinical trial and more studies means more money spent and more time lost. I can't remember the name of the drug anymore, but a couple of years ago another company was told by the FDA that they needed more studies and they just gave up because they would never be able to make their money back.

That's what makes me wonder if the manufacturer will just give up on Lemtrada for the US and put Campath back on the market to be used off label for MS - if the FDA allows it. That will be much less expensive than running new studies.

With other countries already having approved Lemtrada, smaller aftermarket studies will get done over time that the manufacturer could use to submit to the FDA that won't cost them as much as running new studies now.

I don't think Lemtrada is dead in the US. But I think it will be interesting to see which route the manufacturer takes to try to balance the loss of money on more studies with the need for a return on investment ASAP.

[Marco]

MSer102 - agree 100%.

I would just add there will be litigation between Genzyme, Sanofi and investors. Campath was the drug that made that deal happen and I'm sure they were mislead during the procurement process.

It also makes you wonder why the FDA saw "tortured evidence" that led them to question Lemtrada, but EU, Canadian and other regulators did not. The other questions should be why Lemtrada was recommended for approval after the concerns were brought up by the panel?

I would also imagine that doctors will be more reluctant to prescribe "Campath" off-label considering this fiasco. MS patients may be upset with the FDA, but I believe they made the right call. When drug manufacturers use poorly-designed trials and play fast and loose with the results - drugs should not be approved. Genzyme and only Genzyme is to blame.

[batman12]

Personally I think the FDA has something against induction therapies, first movectro and now lemtrada

Campath is as close a thing as there is to a 'cure' for rrmsers why shouldn't people with ms decide what risks they want to take?

[MSer102]

why shouldn't people with ms decide what risks they want to take?

We should. But we also need to know what realistic benefits we're going to get for the risks we take.

The problem with the Lemtrada studies is that the manufacturer intentionally manipulated the data to make the effectiveness of Lemtrada look better than it really is. So there would be no way someone with MS could make a truly informed decision about what risks to take. That "as close a thing as there is to a 'cure'" impression was apparently built on a lie.

A couple of years from now the manufacturer will get to say, "We're sorry we lied about the effectiveness of our medicine. It's only half as effective as we told you it was. And we're sorry that you had that nasty flare that we told you you probably weren't going to have. And so sorry that you now have 2 more lifetime diseases to deal with, for not much more effectiveness than that other medicine you were taking that didn't have the same serious risks. But hey, you said you wanted to be the one to decide what risks to take without knowing all the facts."

The first person who is seriously damaged by Lemtrada is going to be screaming to their local regulatory agency about why they didn't protect them from such a dangerous drug when they knew the company had lied about the data.

Everybody wants what they want until they find out the realities of what it means to get it.

I have to agree with Marco. Genzyme has only itself to blame.

[Marco]

This isn't the first time that Genzyme has run into trouble with the FDA. In 2008, an active viral contamination was found in their manufacturing process during a FDA inspection.A few months later, additional contaminants (bits of steel, rubber and fiber) was found in their products manufactured at the same plant. In 2009, the FDA warned Genzyme about shortcomings in their operations (from a 2008 inspection. Genzyme was cited for failing to establish and follow written procedures to prevent contamination of sterild drug products. Computer systems were found to be using invalid quality check formulas for the manufacturing verification process. Additional problems were identified in maintenance and monitoring operations. In 2010, Genzyme coughed up $175 million in profits from that particular plant.

In 2011, Sanofi purchased Genzyme, including the rights to Lemtrada and Aubagio, for $20.1 billion USD. Genzyme had projected peak Lemtrada sales of $3.5 billion a year and annual Aubagio sales of roughly $500 million.

This November, a FDA staff report expressed significant concerns about Lemtrada's safety, efficacy, the way drug trials were conducted and the results interpreted. The Peripheral and Central Nervous System Drugs Advisory Committee voted 14-2, that Genzyme has not provided substantial evidence of improvement in disability. Even with the above negative recommendation, an FDA advisory committee voted 12-6 in favor of Lemtrada's approval. Neither vote was binding on the ultimate FDA decision.

Already a couple of law firms are investigating Sanofi, concerning whether they made false and misleading statements and failed to disclose that:

• Sanofi had materially misrepresented the safety and efficacy of Lemtrada in public statements to investors;
• the design of the Lemtrada 323 and 324 trials had been materially misrepresented to investors;
• Sanofi lacked adequate internal controls; and
• Sanofi lacked a reasonable basis for its positive statements about Lemtrada and its prospects.

I also previously commented on rebranding the name from Campath to Lemtrada for the primary purpose of increasing profits. Campath could have come to market cheaper than all other available medications, but instead Sanofi got greedy. The UK has now requested additional cost information from Sanofi to provide cost-benefit information to the U.K. National Health Service. I would not be surprised if the U.K. National Health Service refuses to pay Sanofi's asking price.

I am disappointed that another treatment for MS did not make it to the US, but glad that someone is holding drug companies accountable for their claims BEFORE patients are unnecessarily injured.

[Mable]

Wait, how do you guys get that Sanofi manipulated the data? My understanding was that they used a questionable trial design. HOWEVER, the FDA APPROVED that trial design before Sanofi launched its trial.

The problem, as I understand it, was that the trial tried to compare Lemtrada to one of the Interferons. It was very apparent to the subjects who was getting which treatment. So, the trial wasn't at all blind.

When Sanofi submitted the data, the FDA decided it didn't like the trial design after all. My wild guess is that's the grounds the company will appeal on.

[Mable]

And by the way...I hadn't thought of that alternative scenario, MSer102. That's actually a positive, since the drug would be more affordable if you could find someone to prescribe it.

[Mable]

And finally...Marco! You know I hold you and MSer102 in high regard. I hope you both will take my comments in the spirit I intend them, which is lively conversation. Believe me, I want more effective and less expensive drugs the same as both of you.

Okay, one more comment: I think the justification for upping the price of Campath is that Genzyme/Sanofi had just sunk significant money into those trials for MS. Those aren't cheap. It wouldn't have been worth doing if they weren't going to make money off the deal.

The plus side of Lemtrada would have been that many of us would have only needed two rounds of treatment. That would have been a bit more than $100k all together, but then we wouldn't have had to continue getting the med. Compare that to my Copaxone which will cost our insurance companies more than a million dollars over the years.

[Marco]

Okay, one more comment: I think the justification for upping the price of Campath is that Genzyme/Sanofi had just sunk significant money into those trials for MS. Those aren't cheap. It wouldn't have been worth doing if they weren't going to make money off the deal.

Mable - I ALWAYS welcome your comments even when they do not agree with mine.

I have often defended the high cost of our medications because of the heavy financial requirements on drug companies. When a single drug trial can run towards $100 million there are high-stakes involved. All the more reason you would expect a seasoned pharmaceutical company to conduct a good drug trial and not make rookie mistakes.

Since, Campath has been on the market for a number of years it carried a lower risk level of being outright denied by the FDA (than brand new drugs). This was one of the selling points Genzyme used with Sanofi. Genzyme had projected peak Lemtrada sales of $3.5 billion a year and used this number during the price negotiations with Sanofi. Sanofi floated the number of $700 million in annual sales -- still 7 times the cost of the most expensive trials. In comparison, Campath had a tough time making $100 million annually as a leukemia drug.

The annual cost of Campath for a leukemia patient was roughly $55-60k for up to 36 treatments (per Genzyme). Others said the annual cost of Campath was as low as $30k. For a MS patient, 8 treatments would be the standard protocol using much less of the drug than leukemia . Doing the math, Campath could have easily been the cheapest MS drug on the market (in the $7-12k range).

From my June 2012 post http://www.msworld.org/forum/showpos...85&postcount=4

What will Lemtrada cost?
Price information is currently unavailable and should be interesting.
Pontificating -> Campath’s effectiveness compared to injectible MS therapies could command a premium in the market place. Currently, Campath is cheaper annually than most other MS treatments. Would Genzyme be able to rename Campath (leukemia medicine) to Lemtrada (MS medicine) and increase the cost? Doctors could simply order Campath “off-label” and side-step higher drug pricing.

What I did not expect was for Sanofi to basically dump their Campath leukemia patients for the sole purpose of profiteering on the MS market. I personally want drug companies to be profitable so they can do more R&D. What I cannot support is Sanofi trying to recoup their $20 billion Genzyme purchase at the expense of MS patients. I just think Genzyme pulled one over on Sanofi and now Sanofi is trying to pull one over on the rest of us.

[MSer102]

I just think Genzyme pulled one over on Sanofi and now Sanofi is trying to pull one over on the rest of us.

Oh what a tangled web we weave when first we practice to deceive!

[MSer102]

Wait, how do you guys get that Sanofi manipulated the data? My understanding was that they used a questionable trial design. HOWEVER, the FDA APPROVED that trial design before Sanofi launched its trial.

The problem, as I understand it, was that the trial tried to compare Lemtrada to one of the Interferons. It was very apparent to the subjects who was getting which treatment. So, the trial wasn't at all blind.

The study design wasn't the problem, or at least not the only problem. Nor was the nonblinded comparison to an interferon. Open label studies are done all the time. As long as the studies are identified as being open label and everything else is by the book, not a problem.

I can't find the news story that explained exactly what happened so I can't quote the details. But apparently the manufacturer manipulated the statistics by including data from test subjects that should not have been included in in the calculations in order to make the outcomes look more favorable. So as a result the effectiveness looks better that it really is. So doctors and patients would have no way to make a truly informed decision about benefits vs. risk. That's why that impression that Lemtrada "is the closest thing to a cure" is apparently built on a lie.

The big drug companies have statisticians and management who are paid very well to do their jobs, so this couldn't have been a simple mistake. They deal with regulatory agencies as part of their very existence, so I'm sure they knew exactly what they were doing but were arrogant enough to think that nobody would notice.

The question has come up about how Lemtrada got approved by other agencies in other parts of the world. Good question. Maybe no one at the other agencies looked closely enough at the study design or the statistics to see what was going on, or they did and they didn't care that the statistics were manipulated and the results were falsified. Both of those scenarios are pretty unsettling to me.