2362_ASCO_biosimilars_blog_image-468431-editedAs always, clinical innovation dominated the conversation at ASCO 2018, but many attendees also made time to attend sessions on value and financial burden, where biosimilars were a frequent topic. With more than 40 biosimilars already approved in the EU, and rituximab, trastuzumab and bevacizumab biosimilars approaching launch in the U.S., biosimilars will play a major role in the future oncology landscape. 

At ASCO, oncologists worked to understand the product class, the available clinical and real-world data, and the impact that biosimilars will have on their practice. During the presentations and discussions at the conference, there was a clear sense of consensus around three topics: 

1. The data for biosimilars looks solid. Multiple biosimilar clinical trials demonstrated non-inferiority vs. the reference product, and various post-marketing studies showed very consistent real-world outcomes. At one biosimilar session, “The Arrival of Biosimilars,” investigators presented several examples:

  • PF-06439535, a candidate bevacizumab biosimilar that matched Avastin’s overall response rate in a non-small-cell lung cancer trial
  • Trastuzumab-dkst (also known as Ogviri), which achieved highly similar 48-week survival results vs. Herceptin
  • Sandoz’s biosimilar filgrastim, which demonstrated similar efficacy vs. the reference product in controlling febrile neutropenia in a large post-marketing trial
There are many more trials in progress, with scrutiny to see what longer-term experience yields, but for now it seems unlikely that trial failures will be a major barrier for most biosimilars.
 
2. Payers will drive biosimilar adoption, directly or indirectly. Oncologists expect to receive substantial and growing pressure from payers to use biosimilars. In the simplest cases, payers may use familiar mechanisms to directly mandate usage: For example, prior authorization may require the use of biosimilars in treatment-naïve patients. More broadly, some presenters at ASCO expected payers to leverage the entry of biosimilars to transfer some of the financial risk associated with higher-cost treatments from payer organizations to practices, including more generous reimbursement for lower-cost biosimilars vs. higher-cost reference products. Some speculated that the price differential might even trickle down to patients, with lower out-of-pocket costs for patients who receive a biosimilar, though this may be unlikely with infused products like trastuzumab, bevacizumab and rituximab.
 
3. Decreased costs will be the key incentive to use biosimilars. Oncologists aren’t thrilled at the prospect of more outside influence on their treatment decisions, but most are willing to accept these controls in exchange for lower cost. Physicians are acutely aware that cancer therapy costs are high and rising, with the global spend currently around $100 billion and predicted to rise to $150 billion by 2020. Society at large recognizes the problem, too, with 90% of Americans saying that the cost of cancer drugs is too high.

Given the relatively modest discounts for biosimilars launched so far, many physicians have been skeptical of how much they will help control costs, but at an evening continuing medical education session, PharmD Ed Li shared some analyses showing how biosimilars can in fact drive down spending: First, drug categories where biosimilars have already launched in Europe have seen broad price declines, with steeper reductions in specific markets. Second, because the base prices for biologics tend to be so much higher than for small molecules, even a relatively modest discount can lead to considerable absolute savings. For example, a roughly 30% discount for rituximab, bevacizumab and trastuzumab could generate similar absolute savings to about a 90% discount seen for a trio of chemo drugs after generic entry. 

How Will Hesitation Around Data Questions Impact Biosimilar Uptake?

Despite the areas of consensus, uncertainty still lingered around several key questions, especially oncologist comfort with extrapolation and interchangeability. Every biosimilar session at ASCO spent some time on the topic of extrapolation, the concept that a biosimilar that demonstrates equivalence to the reference product for one indication can be approved for use across all of the reference product’s indications. Extrapolation is the most fundamental leap that physicians will need to make for biosimilars to be viable: Many are clearly hesitant about using a product without the level of clinical data they’re accustomed to with new products, but excessive data requirements will increase barriers to market entry, limit competition and ultimately limit the savings that biosimilars can provide. Some attendees did note that oncologists are very comfortable prescribing drugs with limited data in other situations (such as off-label use supported by guidelines), and that a similar comfort may develop around biosimilar extrapolation. 

Though less of a focus than extrapolation, the concept of interchangeability was widely discussed as well. In addition to approval as a biosimilar, manufacturers can choose to pursue an “interchangeable” designation for their biosimilar. This designation requires an additional clinical trial, demonstrating that patients can switch between the originator and the biosimilar and back again without adverse effects in efficacy or safety. If a biosimilar achieves interchangeability, pharmacists may substitute the biosimilar for the reference product without asking the prescribing physician (similar to the “pharmacy-level substitution” that applies to small-molecule generics today). Outside of oncology, Boehringer Ingelheim has announced that it is pursuing interchangeability for its adalimumab biosimilar, but it remains unclear if interchangeability will play a major role in oncology. Several participants noted that due to the more sensitive nature of oncology, pharmacists may feel uncomfortable switching out a reference product for a biosimilar without explicit consent from an oncologist.

While these uncertainties are real, and others—such as the role that patients will play in biosimilar adoption—have yet to be worked out, some have an outlook for quicker adoption: As Dr. Sanjiv Agarwala put it in one presentation, “Biosimilars are here… and you will be using them whether you like it or not.” However, that has yet to be proven in the U.S. Furthermore, the biosimilars sessions at ASCO were somewhat sparsely attended. As one presenter put it, “It’s hard to get excited about something that’s exactly the same as what you’re used to.” Yet as therapeutic biosimilars launch in the U.S., there’s certain to be more buzz and reaction to determine how to approach them than what we saw recently at ASCO.


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Topics: oncology, Biosimilars, oncology manufacturer, payers, ASCO 2018, clinical innovation, clinical data