Annual Review - May 2006
Every May, to coincide with the publication date of the print version of Pharmaprojects,
we take the opportunity to examine the data held in the database as a whole, look
for trends, and identify the winners and losers over the past 12 months. Among
the analyses featured are trends by total number of drugs in R&D, and examinations
of R&D drugs by status, company, therapy and pharmacology. Although developments
can move rapidly in the pharmaceutical world, trends may be only discernible over
a period of years, so we have often compared last year’s data to that of the previous
years', to try to understand the direction in which R&D is moving.
Total R&D projects – plateauing out?
The total number of drugs in active development stands this year at 7,406, up
1.1% on the previous year’s total. However, as graph 1 shows, the overall trend
still seems to be a plateauing out from the significant increases seen in the
overall pipeline size in the early part of the current decade. Although 2005 was
a slightly more productive year than the very poor 2004 in terms of numbers of
new active substances reaching the market, it still seems as though this lack
of productivity may be one reason why the expansion of the pipeline has been pegged
back.
Graph 1
Total R&D projects reported in Pharmaprojects each May, 1998-2005
The number of new drugs entering the pipeline in 2005-6 was 1,840, slightly higher
than the previous year’s 1,817 but still well down on the historical high of 2003-4.
The number of drugs moving from the ‘Active’ to the ‘Ceased’ file in Pharmaprojects
(ie those newly labelled as Discontinued, Withdrawn or No Development Reported)
was 1,938, slightly lower than the 2,007 making the same move last year. Of those,
only 7.5% were actually confirmed as discontinued by companies. The larger proportion
have been labelled as No Development Reported – fortunately, as >90% of drugs
marked this way never return to active development, we can be confident that they
too are genuine leavers for the pipeline. These new Ceased drugs bring the total
number of drugs in this section of the database to 25,716, while there are a further
2,372 in the Fully-Launched section. Thus the total number of drugs recorded in
the Pharmaprojects database in all three sections (Active, Ceased and Fully-Launched)
has now reached a grand total of 35,494.
The Phase II pile-up continues
Moving to look at the pipeline by stage of development, there has been another
significant increase in the number of drugs in Phase II, which at 1,309 is up
10% on the 2005 figure. However, once again, increased numbers of drugs in the
Phase I and Phase II stages have not fed through to the all-important Phase III
stage, which with 423 drugs, is virtually unchanged from last year. This is further
evidence of drugs piling up at the Phase II stage, with an increasing proportion
not making it through to Phase III. In fact, in the calendar year 2005, 28% of
all those drugs positively confirmed as discontinued fell at Phase II, almost
twice the proportion which were dropped at this Phase in 1997. Conversely, the
proportion of drugs discontinued at the preclinical stage has declined. This is
evidence of both more stringent examination of drugs at Phase II, and of companies’
increasing reluctance to reveal the reasons for abandonment of early stage compounds.
Graph 2
Products in active development by stage of development
The lack of increase in the number of candidates at Phase III is continuing cause
for concern for the pharma industry, as it suggests that there is not likely to
be an increased number of first launches in the next year or so.
|
Position 2006 (2005) |
Company |
No of R&D products in 2005 (2004) |
No of own products |
|
1 (1) |
Sanofi-Aventis |
205 (226) |
139 |
|
2 (2) |
GlaxoSmithKline |
181 (170) |
123 |
|
3 (4) |
Merck & Co |
159 (128) |
119 |
|
4 (3) |
Hoffmann-La Roche |
145 (144) |
72 |
|
5 (7) |
Novartis |
123 (109) |
66 |
|
6 (5) |
Johnson & Johnson |
116 (117) |
65 |
|
7 (6) |
Pfizer |
109 (115) |
68 |
|
8 (8) |
AstraZeneca |
108 (105) |
81 |
|
9 (12) |
Astellas |
89 (68) |
52 |
|
10 (10) |
Bristol-Myers Squibb |
81 (84) |
50 |
|
11 (9) |
Wyeth |
81 (90) |
57 |
|
12 (-) |
Daiichi Sankyo |
80 (-) |
55 |
|
13 (-) |
Bioaccelerate |
76 (-) |
70 |
|
14 (11) |
Eli Lilly |
69 (76) |
43 |
|
15 (13) |
Abbott |
55 (66) |
32 |
|
16 (18) |
Takeda |
53 (49) |
20 |
|
17 (14) |
Schering AG |
52 (61) |
29 |
|
18 (21) |
Amgen |
52 (43) |
39 |
|
19 (24) |
Solvay |
52 (41) |
32 |
|
20 (23) |
Azko Nobel |
51 (41) |
39 |
|
21 (16) |
Schering-Plough |
50 (51) |
26 |
|
22 (15) |
Genzyme |
47 (56) |
32 |
|
23 (164) |
Crucell |
38 (11) |
33 |
|
24 (25) |
Medarex |
38 (40) |
29 |
|
25 (22) |
Eisai |
37 (43) |
23 |
Table 1
Top 25 companies based on the number of products in their R&D pipelines
The top 25 companies in terms of numbers of drugs in active R&D are listed
in Table 1. This shows Sanofi-Aventis holding onto its position at the top of
the table, the effects of post-merger consolidation not being sufficient as yet
to end its reign. GlaxoSmithKline is not far behind though, with an increase in
its pipeline size which exactly mirrors the decrease seen in the previous year.
Of particular interest is the first ever entry of a Japanese company into the
Top 10, with Astellas climbing to number 9 just a year after its formation. A
more recently merged Japanese company is Daiichi Sankyo, which is this year’s
highest new entry at number 12. Added to a further advance for Takeda, this shows
the Japanese pharmaceutical industry coming of age on the global stage.
Also of note is further growth in the size of Merck & Co’s pipeline, as the
company battles hard to escape the shadow cast by the Vioxx withdrawal. Amgen
and Akzo Nobel are other companies which show significant proportional increases
of the number of drugs that they have in R&D. Another high new entrant is
Bioaccelerate, although this company is in fact an umbrella organisation which
oversees a number of smaller companies’ development pipelines.
Dropping out of the Top 25 this year are Lexicon Genetics, and Chiron, the latter
of which will shortly be absorbed into Novartis once its takeover is approved.
This will move Novartis up a further place to number four, with a pipeline of
158 projects. The proposed Bayer/Merck KGaA tie-up will see this new entity reach
number 15 in our chart.
The overall number of companies involved in pharma R&D has increased again,
as evidenced by data in graph 3. However, this year’s increase from 1,621 to 1,633
companies is the smallest ever recorded, providing a further indication that a
growth period for the pharmaceutical industry has come to an end. Further evidence
for this is the fact that the number of companies at the bottom end of the pharma
R&D pyramid has declined for the first time. This year, we report 389 companies
with just one candidate, a fall from 416 last year, and 253 companies with two
candidates (261 last year). This drop is a cause for concern as it is a useful
measure for assessing the healthiness of the industry.
Graph 3
The number of companies with active R&D projects
Therapies – big increase in antidiabetics
Table 2 lists the top 25 therapeutic categories by pipeline size out of the 218
different therapeutic areas used by Pharmaprojects to classify drugs. For the
twelfth year running, the two major anticancer categories at the top of the table
have posted very significant increases, and now account for 23.1% of all drugs
in development.
|
Position 2006 (2005) |
Therapy category (code) |
No of products 2006 (2005) |
|
1 (1) |
Anticancer, other (K6Z) |
1093 (1023) |
|
2 (2) |
Anticancer, immunological (K3) |
616 (574) |
|
3 (5) |
Antidiabetic (A10B) |
344 (313) |
|
4 (6) |
Prophylactic vaccine (J7A1) |
341 (308) |
|
5 (3) |
Anaglesic, other (N2Z) |
337 (324) |
|
6 (4) |
Cardiovascular (C9Z) |
323 (323) |
|
7 (7) |
Cognition enhancer (N6D) |
296 (290) |
|
8 (9) |
Antiasthma (R8A) |
275 (262) |
|
9 (8) |
Ant-inflammatory (M1A1) |
267 (265) |
|
10 (14) |
Recombinant vaccine (T2B) |
261 (234) |
|
11 (11) |
Antiviral, other (J5Z) |
245 (249) |
|
12 (10) |
Neuroprotective (N7C) |
245 (261) |
|
13 (13) |
GI inflammatory/bowel disorders (A16) |
242 (236) |
|
14 (12) |
Immunosuppressant (I5) |
236 (236) |
|
15 (15) |
Opthalmological (S1Z) |
224 (198) |
|
16 (16) |
Gene Therapy (T4A) |
200 (193) |
|
17 (17) |
Hypolipaemic/antiatherosclerosis (C10) |
197 (192) |
|
18 (22) |
Antiarthritic, other (M2C) |
194 (169) |
|
19 (18) |
Recombinant, other (T2Z) |
188 (185) |
|
20 (24) |
Urological (G4Z) |
187 (166) |
|
21 (19) |
Antiarthritic, other (M2Z) |
179 (181) |
|
22 (25) |
Antiparkinsonian (N4A) |
178 (164) |
|
23 (23) |
Multiple sclerosis treatment (N7A) |
176 (166) |
|
24 (26) |
Symptomatic antidiabetic (A10C) |
171 (162) |
|
25 (21) |
Antiviral, anti-HIV (J5A) |
168 (175) |
Table 2
Top 25 therapeutic cateories
Overall 28.2% of pipeline projects are targeted against cancer, indicating that
oncological agents account for almost a third of drugs in R&D. This figure
has consistently increased year-on-year, as the industry focuses on this massive
killer which will affect one in three of us in our lifetimes. It is also an area
which has made huge strides therapeutically, and one for which targeted treatments
can command high prices.
Elsewhere, diabetes is another area which continues to see growth, as the prevalence
of the disease rises due to poor western diets. The 10% growth in the size of
the antidiabetic pipeline is certainly significant. Vaccine R&D has increased
by an even greater percentage, as emerging infections continue to challenge the
global community. Also posting an increase, although slipping down the chart,
is the analgesic category, which continues to build on rises reported last year.
Also of interest are the fact that gene therapy has arrested its decline, and
Parkinson’s disease and multiple sclerosis appear to be other growth areas.
Pharmacologies – anticancer strategies advance
The big winners this year in terms of pharmacological strategy very much reflect
the changes in therapeutic focus just discussed. The largest rise is made by the
microtubule stimulant category, which covers drugs in the taxoid anticancer class,
climbing from number 28 to number 12. Angiogenesis inhibition also strengthens
its hold on the number 2 position, despite only 6% of its drugs having made it
to pre-registration, registration or launch so far. Somewhat counterintuitively,
COX-2 inhibition rises up the table for the second year running following the
high profile withdrawals of Vioxx and Bextra. Tumour necrosis factor α antagonists,
mainly used in inflammatory conditions such as arthritis but under investigation
for a wide variety of conditions, move back into the Top 10.
|
Position 2006 (2005) |
Pharmacological activity (code) |
No of products 2006 (2005) |
% PR, R or L |
|
1 (1) |
Immunostimulant (IM+) |
776 (727) |
8 |
|
2 (2) |
Angiogenesis inhibitor (ANGG-) |
174 (158) |
6 |
|
3 (3) |
Apoptosis agonist (APOP+) |
137 (151) |
5 |
|
4 (5) |
DNA antagonist (DNA-) |
96 (92) |
14 |
|
5 (4) |
Immunosuppressant (IM-) |
82 (98) |
21 |
|
6 (6) |
Topoisomerase 2 inhibitor (TO-2-) |
73 (77) |
18 |
|
7 (12) |
Tumour necrosis factor a antagonist (TNF-A-) |
62 (57) |
13 |
|
8 (11) |
Cyclooxygenase 2 inhibitor (OX-C-2-) |
62 (59) |
37 |
|
9 (8) |
Opiod u receptor agonist (OPI-M+) |
55 (63) |
20 |
|
10 (9) |
Estrogen agonist (ESTR+) |
55 (61) |
45 |
|
11 (10) |
Sodium channel antagonist (CHA-NA-) |
55 (60) |
18 |
|
12 (28) |
Microtubule stimulant (MICTUBE+) |
53 (39) |
11 |
|
13 (13) |
5-HT reuptake inhibitor (5HTU-) |
53 (56) |
30 |
|
14 (7) |
Cell wall synthesis inhibitor (SY-CW-) |
52 (66) |
31 |
|
15 (20) |
Calcium channel antagonist (CHA-CA-) |
47 (42) |
30 |
|
16 (16) |
Insulin agonist (INS+) |
45 (43) |
18 |
|
17 (15) |
Lipocortins synthesis agonist (CHA-CA-) |
44 (45) |
41 |
|
18 (14) |
Gene expression inhibitor (GE-EXP-) |
44 (47) |
0 |
|
19 (17) |
T-cell stimulant (LYM-T+) |
42 (43) |
0 |
|
20 (30) |
Protein 50S ribosomal subunit inhibitor (PRT-50S-) |
42 (38) |
24 |
Table 3
Top pharmacological activities
There have now been a grand total of 1,668 separate pharmacological drug development
strategies reported by Pharmaprojects, indicating that 56 new strategies were
identified over the course of 2005-6. As this is a smaller increase than seen
in previous years, it could be seen as further evidence of a slowdown in the rate
of expansion of the industry. The total number of drug protein targets which are
or have been investigated over the course of the 26 years of Pharmaprojects’ existence
has increased this year from 1,379 to 1,451, as we continue to refine our recently-introduced
protein target data.
A critical year ahead?
Overall, the data from this year’s Pharmaprojects Annual Report would appear
to confirm trends that appeared tentative last year. The picture is that of a
period of expansion definitely coming to an end, and growth in the pipeline slowing
so as to become virtually static. In a sense, the next twelve months could be
critical if the industry is to avoid the potentially embarrassing spectacle of
pipeline growth sliding into reverse. This would not be good news for pharma,
which has spent billions on new technology and has so far failed to see a good
return on its investment. As we have frequently commented, advances have so far
failed to produce an improvement in candidate quality, leading to too-high attrition
rates at Phase II and a consequent shortfall in the number of innovative new drugs
reaching the market. This is an issue which the industry simply must address if
it is to avoid going into a potentially damaging decline. Next year’s set of statistics
should prove fascinating.
Ian Lloyd
Managing Editor
Top
.gif)
