How are biosimilars going to affect patients with rheumatic diseases?

CreakyJoints, and its parent organization, the Global Healthy Living Foundation, welcomes biosimilars to our treatment landscape. We expect the cost savings to affect the patients’ bottom line—their wallets or their pocketbooks&mdash;and we as a community will embrace all treatments to manage our disease because we remember life before these treatments, and we’re optimistic and hopeful for our lives as a result of these treatments.  

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Seth Ginsberg, co-founder and president of the Global Healthy Living Foundation, explains that his organization welcomes biosimilars to the treatment landscape.

Seth Ginsberg: Biosimilars and Rheumatic Diseases

What do you want biosimilar developers to know about patients with inflammatory diseases?

There remains an unmet need for safe and effective treatments for inflammatory diseases. We support the research, development, and marketing of biosimilars to our community and related patient communities.

There are no words that can accurately summarize what biologics have meant to our community of patients. They have changed our lives. I remember when we created CreakyJoints back in 1999, from my dorm room bunk bed in the first year of college. We began by holding community-based patient events in libraries and community centers all around the country. One thing that sticks out in my mind is the instruction we’d give the meeting planners for those events—they’d set up 100 chairs for the event, but right before it started, pull the front right quadrant of 25 chairs so we’d make room for people with mobility assistance devices like wheelchairs or walkers.

Today, when we hold a patient event, if there is 1 wheelchair, it’s the outlier. This is directly the result of the innovation that has occurred with biologics, and biosimilars represent the continuation and proliferation of that innovation for our community.

As the next wave of therapies—in the form of biosimilars&mdash;comes to market, we must all work together to ensure that the cost savings that are realized by these versions of the treatments make their way to the patients’ purses and wallets.

Seth Ginsberg, co-founder and president of the Global Healthy Living Foundation, explains what biosimilar developers should know about patients with rheumatic diseases. 

Seth Ginsberg: What Biosimilar Developers Should Know About the Rheumatic Disease Community

In your experience, are value frameworks, such as those developed by NCCN and ASCO, being implemented in clinical practice?

I think value frameworks are being implemented in practice. I think people use guidelines internationally and that they find them very helpful and important.

Interestingly, sometimes people are so concrete with the guidelines [that] it results in more peer-to-peer reviews for patients because they’ll say, “Well you know, you can’t get that drug because it said that they only had 2 lines of therapy there and that patient had 3 lines.” And then we’re like, “Well, it’s not going to make that big of a difference.” Or, they only had 1 and it said the trial was only done in patients that had 2 lines of therapy. You can become very, very concrete in terms of how you interpret those guidelines.

Overall, I think guidelines are important, they give a consensus approach, they take the literature and best practices and provide that information for busy practitioners who are treating many different cancers and provide them essentially with back up.

Also, the guidelines generally provide patient-friendly forms of their guideline information, and that’s incredibly important. We want our patients to be educated as much as possible about what options exist, and it allows patients potentially to participate more in shared decision-making, and to understand when the decisions don’t fit those guidelines.

Hope Rugo, MD, director of the breast oncology clinical trials program at the University of California at San Francisco, discusses guidelines for the treatment of cancer.

Dr Hope Rugo: Value Frameworks and Clinical Practice

What are the key differences between the process for resolving patent disputes under the Biologics Price Competition and Innovation Act (BPCIA) and under Hatch-Waxman?

I’m a regulatory attorney, so I’m going to address it from the perspective of a regulatory attorney. [Intellectual property, IP] attorneys could give you a number of different answers, but I think there’s really 4 main differences.

The first one is for biosimilars, there’s no patent linkage. What I mean by that is, the approval of the application does not depend on the patents. For Hatch-Waxman, there is patent linkage. If a company does not want to challenge a patent, they have to get what’s called a paragraph 3 certification and they cannot get approval for that application until the patent expires. Even if they want to challenge the patents, there’s something called a 30-month-stay, which delays approval of the application until the patent litigation runs.

For biosimilars, there’s no patent linkage. There are processes for resolving patent disputes, but those are completely separate from whether or not FDA will approve the product. That difference is something that FDA specifically requested when the legislation was passed because one of their biggest headaches is the whole Hatch-Waxman patent process. For biosimilars, they just wanted to stay completely out of that.

The second big difference is that there’s no list of patents for biosimilars. So, for small molecule drugs, you’ve got the FDA orange book. In that publication, the FDA lists all of the patents that apply to the brand product. For biosimilars, FDA has what’s called a purple book, but that does not include any of the patents. The idea is that the patents will be identified and litigated through the process that Congress set out. That’s another main difference.

I guess I said there were 4, now I’ve only got 3 [laughter]. But the third difference I would say is the BPCIA, the biosimilar patent process, is actually much more complex than the Hatch-Waxman requirements. I actually didn’t think Congress could come up with something more complex, because the Hatch-Waxman provisions are 

 complex, but they exceeded my wildest expectations and they’ve included an unbelievably complex process for biosimilars.

Scott Lassman, JD, partner in Goodwin's Technology and Life Sciences Group, discusses the differences between patent litigation for biologics and biosimilars under the BPCIA and small-molecule drugs and their generics under the Hatch-Waxman acts.

Scott Lassman: The BPCIA Versus Hatch-Waxman Litigation

What are some trends in state-level legislation concerning substitution of biologics?

Transparency and safety are big themes at the state-level concerning substitution of biologics. We want physicians and patients to be aware of any changes or substitutions that occur. Ultimately, we believe that in order for biosimilar uptake to be successful, confidence needs to be established in the patient and physician communities. This can only happen through transparency. Thirty-six states and Puerto Rico* have passed patient-friendly legislation that, now by law ensures that a doctor and patient are informed of a substitution, and if for some reason a doctor doesn’t think it’s appropriate, they have the opportunity to prevent the substitution.

Seth Ginsberg, co-founder and president of the Global Healthy Living Foundation, discusses trends in state laws that address the eventual substitution of interchangeable biosimilars for reference biologics.

Seth Ginsberg: Trends in State-Level Legislation on Biosimilar Substitution

Do you foresee the FDA stepping in to clarify issues concerning the BPCIA?

Well, they have issued a number of guidance documents and draft guidance documents. I think they’re going to continue to finalize the draft guidance documents they’ve got out there. I don’t think there’s a lot more on the horizon.

The question about [whether they’re] going to do something in response to the court cases is another interesting question; I actually don’t think they are.

The 1 thing they could do, it would be easy, and this is to me the 1 thing they might do, is they could basically say that for biosimilars there is such a thing as tentative approval. That would address some of the issues that have been swirling around as to when you can give the notice that you’re going to start marketing.

That would be very consistent with what they do with [abbreviated new drug applications, aNDAs] and what they do with 505b2 applications, so I don’t think that would be much of a stretch for them. But they really do not want to get involved in any of this BPCIA litigation. I know the courts and some of the litigators are trying to pull them in; I think they’re going to push back and try not to get roped in. At least that’s my guess.

Scott Lassman, JD, partner in Goodwin's Technology and Life Sciences Group, discusses whether the FDA might involve itself in answering the lingering questions concerning the Biologics Price Competition and Innovation Act (BPCIA).

Scott Lassman: FDA and the BPCIA

Humana recently reclassified Herceptin from a preferred drug to a non-preferred drug in some Florida markets. Have you heard of this happening elsewhere?

I haven’t heard of a reclassification to a non-preferred drug. I think that they’re doing that ahead of time in preparation for the biosimilar availability in the next year. I’m guessing that that will happen wholesale, that every regulatory group and mass insurer will change to say trastuzumab is what is preferred, and the type of trastuzumab doesn’t matter.

Hope Rugo, MD, director of the breast oncology clinical trials program at the University of California at San Francisco, discusses how payers might address Herceptin after the advent of biosimilar trastuzumab. 

Dr Hope Rugo: Will Herceptin Become a Non-Preferred Drug?

Which molecular subtype of breast cancer is the most challenging, treatment-wise?

Well, in terms of subtypes of breast cancer, really the challenges are—the challenges are different, but there are 2 areas of great challenge.

One is triple-negative disease that doesn’t respond to chemotherapy. That is a very difficult to treat disease, incredibly frustrating and depressing (of course more so for the patient than for us) but it’s tough as an oncologist.

I think we’re really looking towards immunotherapy being an area for us to be able to manipulate and improve outcome. We should have data about the first phase 3 immunotherapy trial later this year; we’re hopeful in any case with chemotherapy in metastatic disease. We already have some encouraging results but clearly this is very, very challenging.

Brain metastases that are refractory to radiation, incredibly challenging situation. And then the biggest patient population of challenges is [estrogen receptor—positive, ER-positive] disease that we think, “Well we have hormone therapy,” but we see late relapses. In the last month I’ve had a ton of people have a late relapse from ER-positive breast cancer, and they said to me, “Wait a minute I was 15 years out how could I have bone mets now?” or 11 years or 10.5 and you’ve just stopped their 10 years of endocrine therapy.

So, I think that that remains a huge challenge. The understanding of dormancy and pathways that are critical to us to target to try and avoid the survival of these clones that can then recur many, many years later, is really an important area of research.

Hope Rugo, MD, director of the breast oncology clinical trials program at the University of California at San Francisco, describes the challenges associated with treating different subtypes of breast cancer.

Dr Hope Rugo: Treating Breast Cancer Subtypes

What are some of the trends you have identified in recent congressional hearings on drug pricing?

I think that the big issue is drug pricing. I mean, that’s been swirling around since you’ve had the Martin Shkreli issues; I think that’s the driving force. I think it’s interesting to see what the administration’s response has been. Typical congressional response has been, “Let’s start importing drugs from Canada.” The FDA hates that idea, I think not just from a safety point of view, but also it really undercuts the FDA’s authority. Or the other issue is, “Let’s just let the government negotiate prices with companies,” and companies hate that.

Congress and the administration I think have been looking for a middle ground, and the middle ground is, “Let’s fix this by competition. Let’s get more generics approved more quickly, let’s try and get rid of the impediments that are holding that up.”

The same [is happening] with biosimilars: “Let’s try and get those approved more quickly. Are there ways to approve biosimilars that are interchangeable?” That’s why you saw the FDA come out with its draft guidance document, and I know companies are looking to do that. There’s been a lot of activity at the FDA on that.

To me, it’s been interesting to see how the congressional focus on drug pricing has really been reflected in agency policies to try to speed up generics, to address it through competition and market-based solutions rather than the typical standby: “Let’s go to Canada, or let’s tell the companies what the price is going to be.”

Scott Lassman, JD, partner in Goodwin's Technology and Life Sciences Group, discusses trends in recent congressional discussions about the high cost of prescription drugs. 

Scott Lassman: Trends in Congressional Concern Over Drug Pricing

Are other breast cancer specialists looking forward to Mylan’s biosimilar trastuzumab coming to market? Are you getting questions from physicians about the biosimilar?

We haven’t really seen questions in the [United States] about biosimilars yet. I think there’s a lot of interest in understanding what a biosimilar is, [and] how the different trials have looked at biosimilars because there are many, many now out there, all looking for regulatory approval in addition to the drugs that are already approved in the [United States] and Europe.

But, I think that, because there’s a lot of experience with biosimilars in rheumatologic disease, there is a greater appreciation for the importance of biosimilars in oncology.

I think once the drugs are available, there’s going to be a big need for education and understanding of where these drugs should be and how comfortable people feel with them. But right now, I think in the United States because we can’t use them yet, that the main interest has been in supportive care and in rheumatologic disease.

Hope Rugo, MD, director of the breast oncology clinical trials program at the University of California at San Francisco, disucusses the conversations she is having and expects to have with fellow prescribers about biosimilars in oncology.

Interviews