Word From the Adalimumab Front: A Conversation With Molly Burich, MS, Boehringer Ingelheim: Part 1

In the first portion of a two-part interview with Molly Burich, MS, Director, Public Policy: Biosimilars and Pipeline, Boehringer Ingelheim, we cover the challenges of driving biosimilar uptake, as well as the unique situation that has focused this manufacturer’s attention on biosimilars and interchangeability. 

BR&R: The viability of the US biosimilar industry is being challenged if companies cannot rely on revenue from switching, especially for the autoimmune category.

Molly Burich, Boehringer Ingelheim
Molly Burich, MS

Molly Burich: Yes, biosimilar uptake is certainly going to be dependent on switching. But switching comes in a few different types. One case involves patients who are going to be switched to a therapy with a different mechanism of action. Perhaps their existing therapy no longer works (or didn’t work in the first place).

Another case is medication substitution by the physician. The doctor drives that decision to switch the patient either to a biosimilar or to an interchangeable.

Lastly is automatic substitution, which will come as a result of interchangeability and enabled by state laws. However, that is only in play once a product gains the interchangeability designation.

All of those are important components, but certainly switching overall is an important part of the market viability.

BR&R: When we’re talking about automatic switching, multiple stakeholders are involved, including the prescribers, pharmacies, payers, patients. And none of it matters if we don’t have an interchangeable product or even final guidelines from the FDA on interchangeability. In retrospect, should we have made automatic switching for biosimilars based on something other than interchangeability?

Burich: There are a lot of stakeholders involved and this is. why multiple ways of switching will likely occur. In terms of switching, interchangeability allows pharmacists to switch one reference product prescription for an interchangeable one without intervention of the physician at the front end—pending state laws of course. The physician must be notified of the change.

In our opinion though, automatic switching is certainly not the only way to drive uptake of biosimilars. We believe physician-driven switching and payer-drive substitution via formulary decision-making are very important to drive the uptake of biosimilars.

BOEHRINGER INGELHEIM’S SINGULAR PRODUCT FOCUS

BR&R: Biosimilar utilization, and the overall market, has been growing slowly since the first biosimilar approval. Prospective biosimilar manufacturers have tended to jump into the market with both feet, filling their pipelines with multiple biosimilar agents. Boehringer Ingelheim may be the only major manufacturer with a single biosimilar listed on its pipeline web page. Is the company in a wait-and-see mode, to see if the industry will survive? Or is Boehringer making further investments in biosimilar development behind the scenes?

Burich: We are constantly in an evaluation process of our portfolio. Obviously, we are focused on our approved biosimilar Cyltezo® (adalimumab-adbm) and also on interchangeability, here in the U.S. That is our focus area. We believe that the introduction of biosimilars will improve the lives of patients, as well as contribute to the quality and economic sustainability of healthcare systems.

INTERCHANGEABILITY: MISUNDERSTOOD BUT NO SILVER BULLET

BR&R: The issues around interchangeability are particularly frustrating. At the time the BPCIA was written, was the concept of interchangeability (which does not exist in EMA regulations) an attempt to give prescribers and consumers a warm and fuzzy feeling of an AB-rated generic?

Burich: It’s an important question. As you said, when the BPCIA was written, interchangeability was viewed as a sort of silver bullet. The reality is that interchangeability is an important concept, but perhaps it makes more sense for only certain products. As we gain experience in the biosimilar market, we’re starting to see this.

We believe in the concept of interchangeability and in what the FDA has put forth about interchangeability. We do think there are questions about how an interchangeable product may be perceived compared with one that is not interchangeable. In our comments to the FDA, we encouraged the FDA to come out with educational materials that are geared toward talking about interchangeability, and talking about switching. These are all important questions and need to be addressed for the broad stakeholder community. The FDA is obviously best positioned to bring that type of education in the next round of materials they develop.

BR&R: We’ve heard a great deal about people mischaracterizing interchangeable products as being superior to biosimilars (for the same reference product). Why is this differentiation so important?

Burich: This issue speaks to education. All people engaging in the biosimilar space must realize that the designation of interchangeability does not mean it’s a higher-quality, safer, or more-efficacious product. It means that the manufacturer has conducted additional studies required by the FDA to enable that automatic substitution at the pharmacy level.

The FDA has issued clarifying pieces of information and education on their website about this, but there is room for more. The reality is that when a drug is approved as a biosimilar, it has attained the foundational designation proving that the drug is highly similar to the reference biologic, without any clinically meaningful differences. On the other hand, gaining the interchangeability designation is about conducting trials of multiple switches within the patient and expecting the same results in any given to patient. Those are two different distinctions. It proves something different, allowing for automatic substitution to occur.

In part two and the conclusion of this interview, which will be published in a separate post, Molly Burich speaks to Boehringer Ingelheim’s progress in Cytelzo’s interchangeability studies, its plans for the product in Europe in the face of several adalimumab biosimilars launches in the EU, and also the complexity inherent in CMS’s plans to move biologic agents from part B to part D coverage. 

Largest French Hospital System Decides on Infliximab Substitution

Although Celltrion and Pfizer’s Inflectra® was not approved as an interchangeable product to Remicade®, this will generally not matter to US payers when deciding the coverage of the product in patients who have not had anti-TNF treatment in the past. This is of even less importance to French prescribers, where the European Medicines Agency does not have a mandate to rule on the interchangeability of biosimilars. That means it’s entirely up to the health systems and physicians to decide this matter, including whether to allow substitution or switching.

The basic question is whether the evidence exists this biosimilar monoclonal antibody is close enough therapeutically to the innovator product to justify substitution. In a commentary, French physicians stated that substitution is a foregone conclusion in their country. There is a French law forbidding the practice of automatic therapeutic interchange, preventing systematic institution of the practice.

The biosimilar version of infliximab was approved in 2014, and as governments in the EU have generally not taken a stance on substitution, hospitals and other healthcare systems have addressed this issue, building a consensus based on the experience of the Assistance-Publique Hôpitaux de Paris (AP-HP) (this is the largest public hospital group in Europe, accounting for 22,000 beds and caring for 12 million patients). Unlike in the US, infliximab is administered in the hospital setting in France.assistance-publique-hôpitaux-de-paris-office

However, AP-HP does have its version of the typical US Pharmacy & Therapeutics Committee, called the Committee on Medicinal Products (COMED). This hospital system decided that COMED should decide for itself whether infliximab biosimilars yielded essentially equivalent outcomes and on substitution issues within its hospitals. Last year, it came to the conclusion that the two available biosimilars were substitutable for each other and the originator product.

Furthermore, COMED recommended that (1) “a vigorous post-approval surveillance (full traceability) of these products should be implemented in AP-HP” and (2) “physicians should be encouraged to take part in the registries that will be implemented by the medical disciplines concerned in the AP-HP.”

Back in the US, will payers make their own public statements on switching? This is unlikely, owing to the potential for negative press, but it could ease any concerns prescribers have in using biosimilars. Again, the choice of prescription, without an interchangeability designation, is still in the doctor’s hands. It will be largely up to them to speed adoption.