Withers & Rogers issued its report almost a month after KMR Group, a biopharma industry consultancy, released findings of its latest Pharmaceutical Benchmarking Forum (PBF). Companies that submitted data for this analysis were Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck Research Labs, Novartis, Pfizer, Roche, and Sanofi.
KMR found that more than 25% of large molecules in Phase II between 2006 and 2010 reached the market compared to about 10% of small molecules. “One of the reasons that small molecules have fared worse is because most of these companies were already very heavily invested in small molecule work. All the low-hanging fruit was found in the last 10 to 15 years,” explains Scott Martin, a consultant with KMR. “Now, they’re turning toward new technologies, the biotech technologies, and therefore, you’re kind of going in a new area, finding what works.”
KMR reports that 12% of biologics were calculated to advance from preclinical to clinical studies, compared with just 2% of small molecule drugs. The biologics percentage clearing each successive clinical review hurdle grows to 17% at Phase I, 27% at Phase II, leaping to 58% at Phase III, and 82% at the registration phase. For small molecule drugs, according to KMR, success was calculated to be 4% at Phase I, 9% at Phase II, 44% at Phase III, and 78% at registration.
The KMR study did, however, find that industry’s large molecule success rates in development phases have declined in recent years. Martin thus adds a cautionary note: “We’re finding it harder as an industry—I’m talking about the broad R&D industry—to get large molecules to approval, even though they do have a higher success rate all the way up the development pipeline. If you look in three years and you ask, ‘Has the small and large molecule success rate started to even out or not?’ if my view is correct, you’re going to see that these large molecule rates are going to come down.”
In looking beyond success in clinical studies to eventual approval, the Tufts Center for the Study of Drug Development found that large molecules outpaced small molecules 32% to 13% between 1993 and 2004. The study covered the top 50 pharma companies and was published during 2010 in Nature Clinical Pharmacology & Therapeutics. The discrepancy may, however, reflect the small share (15%) of large molecule drugs in the sample of 1,738 new drugs (lead indications). For all molecules, large and small, the approval success rate for the entire study period was 19%.
A few months after the Tufts study was released, a study by the Biotechnology Industry Organization (BIO) and BioMedTracker looked at the success of 4,275 drugs with a total 7,300 indications from 2003 to 2010. Overall success was just 9%–14.5% for lead indications and 3.2% for secondary indications. Most of the drugs studied, though, were small molecule drugs, notes David Thomas, BIO’s director, industry research and analysis.
Overall success rate for lead indications varied from 14% for NMEs to 26% for biologics and 41% for non-NMEs. For secondary indications, success ranged from 3% for NMEs to 7% for biologics to 10% for non-NMEs.