With lots of talk in the industry about declining R&D productivity and many big pharma companies currently restructuring their research models with the aim of not only improving output quantity and quality, but also to reduce the chances of damaging late-stage clinical failures, EP Vantage has conducted a review of recent trends in research failures and highlights the main clinical disappointments of 2008.
Overall, the number of abandoned or suspended products in 2008 fell 15% to 422 pipeline candidates compared with 2007, although interestingly the number of products put on hold almost doubled to 51, as increasing numbers of cash-strapped companies rationalise their pipelines to conserve cash. Meanwhile, 2008 was a major disappointment for the future success of cancer vaccines, accounting for three of the top ten biggest clinical failures (see tables below).
The analysis presented here is based on pipeline and archive consensus forecast data from EvaluatePharma.
Development put on ice
The increase in products, across all stages of development but particularly at the pre-clinical phase, that were put on hold last year is interesting and is most likely a reflection that more companies can no longer afford to develop all their pipeline candidates, causing the products to be temporarily shelved until cash starts to flow again.
|Suspended in R&D|
|Suspended - Filed||1||0||0|
|Suspended - Phase III||5||2||7|
|Suspended - Phase II||17||14||4|
|Suspended - Phase I||6||4||1|
|Suspended - Pre-clinical||18||5||4|
|Suspended - Research project||4||2||13|
|Total (Suspended in R&D)||51||27||29|
|Abandoned in R&D|
|Abandoned - Approved||0||6||1|
|Abandoned - Filed||6||4||14|
|Abandoned - Phase III||57||59||45|
|Abandoned - Phase II||110||134||137|
|Abandoned - Phase I||79||87||88|
|Abandoned - Pre-clinical||78||116||126|
|Abandoned - Research project||41||62||60|
|Total (Abandoned in R&D)||371||468||471|
Credit crunch and cut backs
Whilst Pfizer abandoned the most products last year, mainly as a result of a significant R&D restructuring program which cut back the number of therapy areas the pharma giant will continue to operate in, the interesting aspect of this league table is the emergence of small biotech companies who have had to slash R&D activities to reduce cash burn and ensure short-term survival.
|Count of Abandoned or Suspended Products|
|DevGen||9||Merck & Co||12|
Leaving CNS and endocrine
The only therapeutic areas that showed an increase in the numbers of abandoned products last year were CNS and endocrine, reflecting the increased developmental and regulatory risk associated with developing drugs in these areas; the FDA’s review last year of the requirement for long-term safety data for all new anti-diabetic agents is a case in point (FDA quells political pressure with new diabetes drug guidelines, December 18, 2008).
|Abandoned products by therapeutic category||Count||% of Total||Count||% of Total||Count||% of Total|
|Oncology & Immunomodulators||109||26%||122||25%||131||26%|
|Central Nervous System||77||18%||55||11%||80||16%|
Conventional products for the chop
As sales growth for biotech products gathers pace and increasing numbers of big pharma companies seek to enhance their ability to discover, develop and commercialise biotech-based drugs, it is hardly surprising that the proportion of conventional products abandoned between 2006 and 2008 has steadily increased to represent three-quarters of all pipeline failures last year.
|Abandoned products by technology||Count||% of Total||Count||% of Total||Count||% of Total|
A bad year for cancer vaccines
The biggest clinical disappointment of 2008 was the failure of Myriad Genetics’ Flurizan to demonstrate meaningful efficacy compared to placebo in phase III trials for the treatment of Alzheimer’s disease.
Whilst Myriad Genetics somewhat surprisingly managed to easily overcome this setback (Flurizan failure highlights Myriad's diagnostic potential, June 30, 2008), unfortunately for Favrille, Genitope and Cell Genesys the failures of their respective cancer vaccines in phase III trials has proved almost terminal.
|Key Products Abandoned in 2008||Archive forecast WW sales ($m) as of Jan 2008|
|Product||Technology||Therapeutic subcategory||Company||Termination Date||Abandoned Phase||2008||2010||2012|
|1||Flurizan (Alzheimer's disease)||Chiral chemistry||Nootropics||Myriad Genetics||30-Jun-2008||Phase III||16||334||694|
|2||Sulonex||Small molecule chemistry||Anti-diabetics||Keryx Biopharmaceuticals||10-Mar-2008||Phase III||19||238||485|
|3||SpecifId||Bioengineered vaccine||Immunostimulants||Favrille||27-May-2008||Phase III||17||188||445|
|4||MyVax||Bioengineered vaccine||Immunostimulants||Genitope||10-Mar-2008||Phase III||0||140||399|
|5||AIR Inhaled Insulin||Recombinant product||Anti-diabetics||Eli Lilly||07-Mar-2008||Phase III||-||91||392|
|6||Amibegron (SR 58611)||Small molecule chemistry||Anti-depressants||Sanofi-Aventis||31-Jul-2008||Phase III||-||121||305|
|7||Dacart||Small molecule chemistry||Anti-parasitics||GlaxoSmithKline||29-Feb-2008||Phase III||-||76||226|
|8||MK-0364||Small molecule chemistry||Anti-obesity agents||Merck & Co||02-Oct-2008||Phase III||-||54||217|
|9||GVAX Prostate||Bioengineered vaccine||Immunostimulants||Cell Genesys||16-Oct-2008||Phase III||-||65||215|
|10||TAK-475||Small molecule chemistry||Anti-hyperlipidaemics||Takeda||28-Mar-2008||Phase III||-||62||177|