Are Biosimilars Justice in Competition for Biologics Like Enbrel?
The FDA definition of biosimilars and a pathway to approval
Biosimilars are pharmaceuticals that are similar to biologics such as Enbrel and Humira, but not chemically identical as with generic drugs. If the unique molecules used to create a biologic (from living proteins) such as Enbrel are not cloned, but carefully imitated, they are considered “biosimilar.” In the U.S., 2009 and 2010 laws provide a pathway for FDA approval of biosimilar products, which could include treatments for Rheumatoid Arthritis. “This pathway is provided in the part of the law known as the Biologics Price Competition and Innovation Act (BPCI Act). Under the BPCI Act, a biological product may be demonstrated to be ‘biosimilar’ if data show that, among other things, the product is ‘highly similar’ to an already-approved biological product. Health care professionals and consumers can be assured that FDA will require licensed biosimilar and interchangeable biological products to meet the Agency’s exacting standards of safety and efficacy.” A few biosimilar drugs are already approved in Europe for other conditions (non-rheumatological).
The boldness of biosimilars
As you can guess from the photos, biosimilars were a hot topic at the American College of Rheumatology (ACR) scientific meeting in November. Patients are anxious to see prices drop for rheumatological Biologics. Everyone is anxious to know how similar “similar” will be.
The exhibit pictured belonged to a Korean biosimilar company called Celltrion and featured a biosimilar for infliximab (Remicade). The blindfolded goddess holding scales of justice had a perfectly sculpted body, including quadriceps and feet. Behind her, in a temple structure, a bent victim stood on painfully folded toes holding a candle with gnarled fingers. I’m still trying to figure it all out.
Interesting twist: Enbrel patent extended
Only days after the ACR meeting came the stunning news that Amgen’s patent for Enbrel had been extended by 17 years. The new patent, called “the 182 patent” after its final digits guarantees that biosimilars of Enbrel will not be sold in the U.S. until 2028. According to the New York Times, “Patents now run 20 years from the date of application, to avoid situations like this where an invention gets extended protection because of delays or maneuvers at the patent office. But since this patent was filed before the law changed, it is governed by the old rules and lasts for 17 years from the date of issuance.”
Another twist: Amgen in the biosimilar business
Large pharmaceutical companies like Enbrel’s Amgen join companies like Celltrion in preparing to develop biosimilar products. Over the last month, Amgen has made news with its partnership with Watson as they plan to create biosimilar cancer treatments. “’Biosimilars provide an exciting long-term growth opportunity for Amgen,’ comments the firm’s Robert A. Bradway, president and CEO.”
“Abbreviated” licensure must ensure safety
The law calls for “an abbreviated” process. We’ll see how abbreviated it will be. Will companies be required to conduct clinical trials that are similar to what has been required for the original products?
The U.S. FDA’s page about the biosimilar pathway statutes says, “The Patient Protection and Affordable Care Act (Affordable Care Act), signed into law by President Obama on March 23, 2010, amends the Public Health Service Act (PHS Act) to create an abbreviated licensure pathway for biological products that are demonstrated to be ‘biosimilar’ to or ‘interchangeable’ with an FDA-licensed biological product.” As the actual pathway unfolds in the U.S., consider the approval of Orencia injections last year. Bristol Myers Squibb (BMS) brought the identical molecule in a new method of delivery. The newer injectable Orencia was even produced with the same manufacturing process and location. Yet, BMS was required to prove by phase III clinical trials that the drug had the same safety and effectiveness as intravenous Orencia. If clinical trials are not done as part of the abbreviated process, the first patients who buy the new treatments could effectively be paying to participate in a post-market clinical trial.
Recommended reading
- Rheumatoid Arthritis Rheumors: 2 Mysteries Solved
- The Rheumatoid Arthritis Commercial Saga
- RA News Headlines, Vol. 6: Ibuprofen for Pain, Orencia Shots, New RA test, RA Inflammation Increases CV Risk
The drugs that we currently have available cause me enough concern and they have been through the full gamete of trials and FDA approvals. I do not think I would want a “bio-similar” that had not been through full trials and FDA approval. While the cost may be significantly less per month, which certainly is a major advantage to many people, I would also be concerned that the insurance carriers would more-or-less force the generics on us by setting a whole new tier of pricing or something similar.
I share your concern that insurance companies may “force” the switch to “biosimilars”. We have found a combination of meds that has given me back a normal life and I do not want to be forced to change any of them.
It is an important point Matthew. No person with this disease should be forced to change medication if he finds something that works! I’ve seen it happen due to the convenience of a doctor or for other non-clinical reasons and the patient never again achieved disease suppression. It is too difficult to find a treatment combination that is effective and it should NEVER be changed without good clinical reason. A battle for the Rheumatoid Patient Foundation.
I understand your concerns about switching to a biosimilar and a eventually lose some of the efficiency of the drug.
My concern here, is that enbrel got an extended period of 17 years to keep dominating the market. This means, for another 17 years, hundreds of thousands of RAD patients all over the world will never access to a biologic drug to treat this awfull dissease, because their underdeveloped economies. This means, they have to stick to early eighties treatments. As it were not enough curse to get this disease, now deal with the lack of treatments because some social-economic reasons. It doesn’t seem that Enbrel will drop their prices, so this is, in the end, a med for the elites. It’s so sad.
I also understand American way of thinking, and I have no problem with it at all. But, just imagine for a second or two, that Aspirine, or, ibuprofen, or any antibiotic you can think of would keep being patented with such prices.
Hell, here were I live, the average citizen salary per year would not be enough to cover that year of an Enbrel treatment.
George, I’m not trying to say they should not make bio-similar drugs or allow them on the market. This just happens to be the first time I have ever had personal concern for what the results of this may be, especially if these drugs are not fully tested and proven to work as well as the original drug or have similar patient safety. When you are healthy you don’t think to much about problems like this (myself until ~6 months ago).
I also agree that the cost is a MAJOR issue for a large portion of the western world and even worse in most other countries. The pricing structure means that if you don’t have good health insurance you probably won’t get these drugs, which is extremely unfortunate for a great many people. I was afraid of getting a rejection letter from my insurance company, in spite of what I pay for my insurance. I am sure if I was not in a group plan through my employer I would be dropped as the Enbrel alone costs more than my premiums, though not a lot more.
Hello Mr. C,
Sorry, I didn’t mean to say that you’re against those drugs, and I do really understand your concerns about efficency and safety of an hypothetical biosimilar.
I am absolutely sure that if any company comes with an equivalent to the enbrel molecule, it would be exhaustively tested by all of the drug safety and efficency administrations. This is nothing to be taken lightly.The Enbrel itself was tested like that before arriving into the market.
What I wanted to express on my previous comment, is that the time when the biologics drugs are available to the general world population, indepently of the religion, politics,economy, has to arrive soon. It’s just like it happened with the MTX, or aspirin, or whatever drug you can think of. I understand, that US companies developed those incredible meds, and the should make the proper profit of them. It’s absolutely logic. But, where’s the limit to it? Have they made enough profit of them? What profit are they expecting to do on it? Not bashing them, I know, the invested LOTS of money in order to arrive with those. But, we have to think further than in an economic point of view. We need some kind of balance: Pharma industry making huge benefits VS general population health
Peace,
George
This is a fascinating discussion. The Biologics like Enbrel were tested for 3 and 4 stages of clinical trials that last several years. The “accelerated” truncated process being suggested by some for biosimilars would eliminate much of that by allowing the companies to use some of the data of the original product and only prove that they are “similar” enough to be treated the same under the law. There is a lot of discussion of this on various websites. The issue of cost is extremely important and these are the most expensive drugs in the world. The issue of safety obviously must be foremost though and looking at the way the FDA treated injectable Orencia with BMS as discussed in the post, I trust that they will do whatever is right to protect American patients. As far as I understand, all Enbrel for sale today is a clone of the original Enbrel – but a biosimilar would be a constructed protein made to imitate the original as much as possible.
Hi George, no offense taken or implied. The downfall to the internet is that all tone and inflection of speech is lost to bare text. I just wanting to clarify my statements and views.
Hi Kelly, the “accelerated” approval process and bio-similar (sounds like close enough) molecule is the part that concerns me. If it isn’t identical it should be fully tested to prove it is safe and effective, simply my opinion based upon not having any idea if it will work properly. In the end the bio-similars could be more effective for some individuals than the original drug. Of course, none of this will be known until someone produces and tests one of these bio-similars.
This is a quote from a good article, I posted the link below-
“Sometimes the antibodies produced in response to a biologic have no effect. Other times they bind and inactivate the biologic, causing disease progression. In still other cases, they can bind to and inactivate a patient’s naturally occurring protein, which means that the patient may be left with no options other than regular blood transfusions.”
“One example of immunogenicity occurred a few years ago when, at the request of the European Health Authorities, Johnson & Johnson made a change in the manufacturing process for its EPREX product – a product that had been marketed for a decade with no evidence of immunogenicity problems. The change caused a serious adverse reaction in a small number of patients. These patients lost their ability to make red blood cells because they produced an antibody (triggered by the EPREX) that inactivated both the administered protein (EPREX) and the body’s natural protein that is essential for red blood cell production. Johnson & Johnson eventually was able to determine the cause of this adverse reaction and correct it, but only after a very lengthy and expensive investigation.”
http://www.bio.org/node/46
I understand the need for less expensive drugs, but I’m deeply concerned that insurers will switch us with no warning. It is not just underdeveloped countries that have a problem. A family member of mine has had severe RA for over 30 years. She lives in New Zealand. The only two bios available are Humira & Enbrel, and she has yet to be allowed either one. This kind of thing is one of the darker sides to socialized medicine.
I find this whole discussion about bio-similars to be a bit confusing. I had no idea that all of the Embrel was “cloned” from the origional! How do they maintain integrity? Wow, I guess I really know nothing about how these drugs are made. But considering that they are biologic, I guess there is a process that might require some digging to understand. I have to admit that I was angry to hear that they had received a 17 year extension on the patent for Embrel as a result of some lame loophole. While there are certainly legitimate concerns about how similar a bio-similar would be and whether our insurance companies would force us to use less expensive bio-similars first or instead as well as concerns about the premarketing testing of these drugs, the expense of the biologics now on the market has put them out of reach of many world wide as well as here in the US.
This is a difficult subject. And one thing I know now is that I need to understand more about how these drugs are made and how bio-similars will be made and tested. Thanks for opening the discussion.
Yes, biosimilars will provide more competition and lower prices, but only for off-patent products and their me-too/follow-on biosimilar (and biobetter and biogeneric) versions. So there will be more and likely cheaper versions of products that are likely already several decades old since their original discovery.
With more generic-like competition and innovator biopharmaceuticals more rapidly losing market share once biosimilars (and biobetters and biogenerics) enter the market, it remains to be seen whether biosimilars will be bad for patients in terms of, ultimately, leading to less R&D and development of new innovative products.
To me, the subject of Biologics to Biosimilars is amazing. I was lucky enough at the American College of Rheumatology science meeting last November to sit in on a discussion of how the similars are made compared to the original bios and it was incredible the amount of science that goes in to creating them. When you look at how bios are actually produced, it’s like watching an alchohol still in operation. Even if they are able to duplicate the similars exactly, the slightest change in how it is “brewed” so to speak (i.e. type of metal used in the process, the matter that is used to cultivate the drug, the syringes or containers the medication is stored in after production)can change the efficacy of the medication to a point that they may even need to do new testing to make sure it is still working the way it is supposed to. That to me is worth additional studies.
Wow, I was hoping that Enbrel would go generic. Without really good insurance, no one other than the quite wealthy can afford it as it is now, and I am concerned about what insurance companies would deem close enough with biosimilars. Close enough might not be good enough to give the help that some patients on biologics now receive. Something definitely needs to be done, though, and I am certainly not against developing more affordable options as long as they work as well and are thoroughly tested. More medical research needs to be done to help patients who are not helped much by current medications, too, or who are not responding at all to the ones on the market.