The BTD pathway - implemented under the Food and Drug Administration Safety and Innovation Act (FDASIA) in 2009 - is designed to fast-track reviews of new drugs for life threatening diseases.
Roche, through its subsidiary Genentech, was the first firm to attain a breakthrough status for a biologic – Gazyva (obinutuzumab) – and earlier this month received such status for its investigational cancer immunotherapy MPDL3280A (anti-PDL1).
Speaking this week at the BioProcess International Summit in Dusseldorf, Germany, Roche’s Head of Technical Development, Biologics Europe, Niklas Engler, said the firm hoped to achieve breakthrough status for a third candidate by the end of the year, but said preparing for BTD meant pre-planning, pragmatism and a certain amount of risk.
“You make a thorough plan years in advance – we planned Gazyva for years, what was going to happen when [in terms of development] – and then [the BTD] and you’re asked to accelerate,” he told delegates, comparing the R&D timeline with a 4-day expedition suddenly cut to just one day. “You really have to skip some of the parts and this comes with a lot of risk.”
In such circumstances Engler said communication with the FDA is crucial, as does the Chemistry, Manufacturing, and Controls (CMC) activities which “may define the critical path.”
Phase III development steps may need to be shortened, and process characterization/validation may need to be accelerated, he said.
Furthermore, with Gazyva, key aspects of the Phase I operations – cell line selection, downstream process, formulation etc – were maintained for later stages and commercialization which means they needed to be adjusted post-launch to ensure supply.
More R&D projects, more knowledge
For a big firm like Roche that may have upwards of twenty different potential BTD programmes on the go at one time the risk is manageable. For small-and mid-sized pharma firms (SMEs) the risk is greater according to Engler, who said some may have trouble in being so flexible with their R&D approaches.
For an SME, “they will have difficulties as they will only have one or two programmes,” he said. “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.”
Of course Roche doesn’t want to waste resources and has to choose the candidates with the highest probability.
“At the heart of the industry is which projects will succeed. The competition is helping us to find the best and most clever ways. A company dealing with a portfolio by itself has an advantage because you gain biological understanding, the platform knowledge to use across projects.
"We are extremely fortunate in a way because when Roche acquired Genentech in 2008 we brought together two different approaches and we can really combine the knowledge and there is so much platforming and even in the more complex candidates in the future there are bits of your platform and processes which will apply."
According to Engler, so far there have been 285 applications for BTD, of which 82 have been granted, and 23 approved (including seven biologics).