Research failure trends in 2008

Analysis

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.
 

  Product Count
  2008 2007 2006
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
       
Total 422 495 500

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
2008   2007
Pfizer 40   AstraZeneca 42
Merck KGaA 16   GlaxoSmithKline 36
Sanofi-Aventis 15   Bayer AG 17
GlaxoSmithKline 13   Pfizer 14
AstraZeneca 10   Novartis 13
DevGen 9   Merck & Co 12
ADVENTRX Pharmaceuticals 8   Roche 11
Bayer AG 8   Sanofi-Aventis 11
Innogenetics 8   Biovitrum 9
Daiichi Sankyo 7   Novavax 8

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).

  2008   2007   2006
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%
Systemic Anti-infectives 61 14%   78 16%   61 12%
Endocrine 36 9%   29 6%   27 5%
Cardiovascular 26 6%   47 9%   58 12%
Musculoskeletal 20 5%   29 6%   26 5%
Respiratory 20 5%   32 6%   30 6%
Gastro-Intestinal 17 4%   24 5%   29 6%
Blood 16 4%   22 4%   10 2%
Dermatology 15 4%   11 2%   13 3%
Genito-Urinary 9 2%   28 6%   17 3%
Various 9 2%   15 3%   13 3%
Sensory Organs 7 2%   3 1%   5 1%
Total 422     495     500  

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.
 

  2008   2007   2006
Abandoned products by technology Count % of Total   Count % of Total   Count % of Total
Conventional 322 76%   368 74%   348 70%
Biotechnology 100 24%   127 26%   152 30%
Total 422     495     500  

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

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