Breakthrough Therapy Designation: Worth The Development Time Crunch, Experts Say

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

When I hear the words “Breakthrough Therapy Designation” (BTD), I immediately picture a gold-embossed certificate with a blue ribbon. After all, the designation is reserved for those candidates that, early on in clinical studies, promise more extraordinary benefits than the current standard-of-care treatments for a disease. Judging from the recent buzz I’ve noticed in the industry, the increasing number of treatments boasting this designation is in no way eliminating its prestige. Rather, it would seem BTD still holds a certain amount of allure, not only from a regulatory perspective, but also because of the challenges it presents for pharma and pushes them to overcome.

Since BTD was launched under the 2012 FDA Safety and Innovation Act (FDASIA), 82 drugs have been named breakthrough therapies, and 23 of these have been approved for release onto the market as of March 2015, according to The Brookings Institution. While 82 might seem like a high number, there have been 293 BTD requests, and the FDA’s rescinding of Merck’s BTD in February for its investigational hepatitis C drug implies that keeping the designation can be just as difficult as getting it in the first place. (Merck’s treatment has since regained its BTD crown — two crowns, in fact, for two smaller patient populations: those with genotype 1 [GT1] with end stage renal disease on hemodialysis and GT4 patients.)

Indeed, the pharma giant’s recent loss of BTD emphasizes the rapid pace at which competitive therapies are entering the market — especially in hot therapeutic areas like hepatitis C. If pharma companies thought remaining innovative and on top of the market was a challenge before BTD, after this incident, it would seem that challenge has been amplified.  Despite some of the industry grumblings about the arguably still too-slow pace at which the FDA might approve a breakthrough, the agency still seems to know what’s up in terms of which needs are and are not being met by current treatments on the market.

In an interview with in-PharmaTechnologist.com, GlobalData analyst Christopher Pace said, “This move [to take away Merck’s HCV treatment BTD] may potentially signify a willingness by the FDA to monitor BTDs in real time and revisit them in response to changes in the standard of care in a particular indication and/or therapy areas…”

BTD Challenges: Why It’s Worth The Effort

Just last week, BTD was the topic of discussion amongst R&D execs during a roundtable hosted by the Tufts Center for the Study of Drug Development. In addition to the benefits of the FDA’s assistance and the (hopefully) quicker timeline (three to five years, as opposed to seven) for getting a drug to market, execs argued that BTD is invaluable because it pushes drug companies and regulators to be flexible and willing to learn from each other.

According to the Tufts announcement, there are, naturally, a number of challenges that arise for sponsors in the process of pursuing a breakthrough designation. For one, execs homed in on the difficulties sponsor companies can have determining what constitutes a serious condition, how effectively current drugs treat the condition, and what unmet health needs exist. The execs argued that pursuing a BTD is “emphatically worth the effort.” This designation requires sponsors to show initiative in building FDA reviews and evaluation points into the study’s development plan, as well as in preparing a development strategy and study design even before meeting with the FDA.

Pursuing this designation also requires that a company have the plans in place to accelerate development and manufacturing as well, said Christopher-Paul Milne, Tufts’ director of research.

Genentech in particular has been vocal when it comes to striving for and realizing the benefits of BTD — most likely because it was the first company to receive this designation for a biologic, Gazyva. In an interview with Trisha Gladd, Bioprocess Online’s chief editor, Senior Director of Pharmaceutical Development at Genentech, Dana Andersen, highlighted several key steps companies should consider when looking to increase CMC development efficiency. In addition to fixing CMC issues upfront, Andersen also emphasized the need to screen sequence candidates early and to “learn from your past experience” and use standard approaches, in turn cutting down on development work.

Judging from Andersen’s discussion, as well as a recent speech by Roche’s Niklas Engler, head of technical development, Biologics Europe, at the BioProcess International Summit in Dusseldorf Germany, perhaps the largest challenge is confronting and accepting the risks inherent in the accelerated development process that accompanies BTD. As Engler said, “You make a thorough plan years in advance…and then [the BTD] and you’re asked to accelerate. You really have to skip some of the parts, and this comes with a lot of risk.” For example, Engler highlighted the need to accelerate process characterization/validation, and to maintain cell line selection, downstream process, and formulation beyond Phase 1 to ensure supply following the product’s launch, in-PharmaTechnologist.com reported.

The size of the company pursuing BTD is also a factor to consider. Small-and-midsized pharma companies (SMEs) are likely to have a more difficult time taking the leaps required by BTD. “[SMEs] will have difficulties as they will only have one or two programs. They strongly believe in their technology and that is what they are pushing for, so I think they will have to probe their investors and get the feedback in way of funding in how much belief there is in their molecule,” Engler said.

However, as the experts in the Tufts roundtable touched upon, it ultimately comes down to determining the appropriate candidate. “Betting on the right data” to ensure the selection of the candidate with the best possible chances of success, according to Engler, is a big part of the process for a larger company, such as Roche, as it approaches BTD programs. While this discussion can lead to some “internal debate,” it seems that it’s these requirements that make a treatment and its company live up to its “breakthrough” label. The designation is just another way of keeping industry competitive and moving forward in the “best and most clever ways,” said Engler.

When facing a shorter timeline, it’s certainly daunting to know “you can’t always do everything you want to do,” Andersen told Bioprocess Online. However, there will always be pressure to fill a pipeline and to do so with limited resources. In being pushed to streamline and accelerate a product’s development, Andersen says the company stands to learn a lot more about the “processes and products that we need to investigate and explore in order to do things better.”