Market Insight - Clinical trials metrics tell all about pharma's R&D investment
19 November 2009
Dr Christine Blazynski

When examining the competitiveness of company pipelines and the extent of firms' commitment to R&D, it is arguably more relevant to consider the number of drug projects as reflected by clinical trials' activity as opposed to the overall number of drugs in the pipeline. Using data from TrialTrove for the 12-month period from September 1st, 2008, to August 31st, 2009, where trial start dates were disclosed in the public domain, trial activity was analysed to determine overall rankings by industry sponsor and company R&D spend per trial.

Looking across all of TrialTrove's therapeutic areas and diseases, the five leading company sponsors with the greatest number of clinical trials initiated during this 12-month study period were Novartis, Roche, GlaxoSmithKline, Pfizer and Lilly (see Table 1). The companies occupying the top three positions shifted compared with rankings for the previous 12-month period, with Novartis and GSK exchanging rankings between third and first place. Lilly moved from ninth place in 2008 to fifth this year, displacing Sanofi-Aventis.

Table 1: Top company-sponsored trial starts comparison

2008 rank	Company	Trial starts*	2009 rank	Company	Trial starts**
1	GlaxoSmithKline	125	1	Novartis	155
2	Roche	120	2	Roche	139
3	Novartis	117	3	GlaxoSmithKline	118
4	Pfizer	116	4	Pfizer	90
5	Sanofi-Aventis	115	5	Lilly	87
6	Johnson & Johnson	90	6	Merck & Co	79
7	AstraZeneca	90	7	Sanofi-Aventis	77
8	Bristol-Myers Squibb	84	8	AstraZeneca	75
9	Lilly	80	9	Bristol-Myers Squibb	62
10	Genentech	74	10	Bayer	51
11	Merck & Co	73	11	Johnson & Johnson	47
12	Bayer	56	12	Boehringer Ingelheim	41
13	Schering-Plough	55	13	Wyeth	37
14	Takeda	53	14	Amgen	33
15	Boehringer Ingelheim	47	15	Takeda/Millennium	30
16	Abbott Laboratories	46	16	Celgene	28
17	Wyeth	40	17	Genzyme	25
18	Eisai	37	18	Forest Laboratories	24
19	Celgene	33	19	Daiichi Sankyo	22
20	Merck KGaA	32	20	Eisai	21
21	UCB Pharma	23	21	Astellas Pharma	19
22	Amgen	21	22	Merck KGaA	17
22	Novo Nordisk	21	23	Lundbeck	15
23	Alcon	18	24	Alcon	14
23	Astellas Pharma	18	24	Ferring	14
23	Lundbeck	18	24	Gilead Sciences	14
24	Genzyme	15	24	Otsuka Pharmaceutical	14
25	Daiichi Sankyo	14	25	Schering-Plough	12
25	Otsuka Pharmaceutical	14	25	Cephalon	12
-	-	-	25	Baxter	12
-	-	-	25	UCB Pharma	12
-	-	-	25	Abbott Laboratories	12

*September 1st, 2007, to August 31st, 2008; **September 1^st, 2008, to August 31st, 2009

Source: TrialTrove; data accessed October 9th, 2009

Moving beyond the top five leading industry trial sponsors, the companies that significantly increased trial sponsorship in the most recent 12-month period compared with the year before include Amgen (moved from 22nd to 14th place), Daiichi Sankyo (25th to 19th), Genzyme (24th to 17th), Lilly (9th to 5th), Merck & Co (11th to 6th) and Wyeth (17th to 13th).

Industry sponsors that dropped down the rankings between the two years include Abbott Laboratories (16th to 25th), Johnson & Johnson (6th to 11th), Schering-Plough (13th to 25th) and UCB Pharma (21st to 25th). Due to Roche's complete buy-out of Genentech in late March 2009, Genentech is no longer included in the 2009 sponsor list. Details in TrialTrove data reveal that 57 of Roche's 139 trial starts for the initial six-month 2009 period originated from Genentech, a decrease from the 74 recorded in 2008.

When trial starts for the 12-month period are compared with the companies' 2008 pharmaceutical sales and R&D spend figures (see Figure 1), there is an overall correlation between the two: more research spend correlates to more trial starts. An important caveat is that not all R&D spend is earmarked for clinical development; however, clinical development is known to consume the greater part of research monies.

Figure 1: Trial activity, pharma sales and R&D spend metrics

Source: TrialTrove; Scrip's Pharmaceutical Company League Tables 2009

A ranking of companies by least spend per trial (a proxy for the effectiveness of companies' R&D spend) reveals several speciality companies as the front runners (see Figure 2). Both Forest and Lundbeck, with a strong focus on CNS diseases, have low spend per trial ratios, as does Celgene, with its cancer focus. The only big pharma players to feature among the 10 companies spending the least per trial are Novartis, Lilly and Bayer.

Figure 2: R&D spend effectiveness and focus on novelty

Source: TrialTrove; Scrip's Pharmaceutical Company League Tables 2009

The top performers in terms of novelty in the pipeline are AstraZeneca (73% of its 75 trials involve a novel pipeline drug) and GSK (71% of 118 trials; see Table 2). The other large pharma industry sponsors with 50% or more of their trials involving pipeline drugs are J&J, Lilly, Pfizer and Bristol-Myers Squibb. It is likely that these companies will be the ones to watch in terms of bringing new products to market in the near term.

Table 2: Leading sponsors of trials investigating pipeline drugs*

Rank by trial starts	Company	% pipeline drug
8	AstraZeneca	73
3	GlaxoSmithKline	71
11	Johnson & Johnson	62
5	Lilly	58
4	Pfizer	56
9	Bristol-Myers Squibb	52
1	Novartis	50
7	Sanofi-Aventis	50
6	Merck & Co	38
10	Bayer	35
12	Boehringer Ingelheim	33
2	Roche	28

*September 1^st, 2008, to August 31^st, 2009

Source: TrialTrove

When R&D spend per trial is adjusted to reflect trial activity for novel drugs, the top 10 spenders are Baxter, UCB, Wyeth, Abbot, Schering-Plough, Takeda, Boehringer Ingelheim, Amgen, Roche and Celgene (see Figure 2). Baxter has by far the largest number of trials focused on novel drug testing.

For those companies with lower percentages of studies involving pipeline drugs, label expansion is the predominant focus of their trials. The other strategy revealed by trial focus is life cycle management involving combination therapies. Among the top 10 companies in terms of overall trial starts during the 12-month period, those whose trial activity is below a two-to-one ratio between spend on trials with novel drugs and launched drugs include BMS, Pfizer, Lilly, GSK and AstraZeneca.

Novartis is a major player in all six of TrialTrove's therapeutic areas; for trials initiated in the 12-month period of analysis, the company ranks no lower than third place in any area (see Table 3). Pfizer enjoys a top five ranking in four of six areas, missing a leader position in infectious diseases and metabolic/endocrinology. The acquisition of Wyeth should boost Pfizer's position in infectious diseases in the near future due to Wyeth's vaccine holdings. Pfizer is also likely to rise up the ranking in oncology post-acquisition.

Table 4: Top five ranking in trial sponsorship*

Therapeutic area	#1	#2	#3	#4	#5
autoimmune/inflammation	Novartis (31)	Roche (15); Pfizer (15); AstraZeneca (15)	GlaxoSmithKline (13)	Boehringer Ingelheim (12)	Johnson & Johnson (7); UCB Pharma (7)
CNS	Pfizer (31)	Lilly (26)	Novartis (17)	AstraZeneca (16)	Lundbeck (15)
cardiovascular	Novartis (16)	Merck & Co (11)	Astellas (9)	Daiichi Sankyo (8); Sanofi-Aventis (8); Pfizer (8)	Bayer (7)
infectious diseases	GlaxoSmithKline (46)	Sanofi-Aventis (21)	Novartis (19)	Merck & Co (12)	Johnson & Johnson (8)
metabolic disease	Merck & Co (16)	Roche (14)	Forest (11); Novartis (11)	AstraZeneca/Bristol-Myers Squibb (9); Lilly (9)	Sanofi-Aventis (8); Boehringer-Ingelheim (8); Novo Nordisk (8)
oncology	Roche (55)	Novartis (37)	Bristol-Myers Squibb (23)	Lilly (20); Celgene (20)	Pfizer (19)

*September 2008 to September 2009

Source: TrialTrove; data accessed September 17th, 2009

Five companies enjoy a strong presence in three therapeutic areas. Roche dominates in oncology with 55 total trial starts. The company has a significant investment in autoimmune/inflammatory disease studies, and in metabolic diseases. Merck & Co is the overall leader in metabolic disease trials, and a close second to Novartis in cardiovascular focused trials. Merck has also made a significant clinical investment in infectious diseases.

Lilly has a significant focus on CNS, trailing Pfizer by only five trial starts. Lilly has also sponsored a significant number of trials in metabolic diseases and in oncology. Sanofi Pasteur, the vaccines division of Sanofi-Aventis, successfully initiated 21 trials in infectious diseases. Sanofi-Aventis is also active in cardiovascular and metabolic disease areas. AstraZeneca shares second place with Roche and Pfizer in the autoimmune/inflammation area, and is a close fourth to Novartis in CNS. In the metabolic disease arena, AstraZeneca has partnered with BMS for a total of nine trial starts.

Beyond assessing company performance, trial activity can reveal other notable trends. For example, among the nearly 2,000 industry-sponsored trials that have disclosed start dates during the 12-month study period, 139 were identified as being designed for registration application. But the data presented here indicate that the industry is involved in significant novel development that demands clinical trials that may not always be included in regulatory filings – unavoidable costs to trial sponsors.

Among the nearly 2,000 Phase II, Phase II/III and Phase III trials initiated, a mere 53 were terminated, and among these, 24 were terminated at Phase III – at first glance not a harbinger of companies' intentions to kill early, kill fast. But, delving into details, Citeline finds that 10 trials never enrolled any patients (they were terminated before the start of enrolment), four were terminated due to lack of efficacy, two for low enrolment, three for internal business reasons and, for five trials, the reason for termination was not publicly disclosed. The number of Phase III trials that actually began enrolling subjects and were subsequently terminated during the 12-month study period was less than 2%! These metrics indicate that last year was respectable in terms of industry stopping clinical development spend before large expenses were incurred.

Dr Christine Blazynski is Citeline's senior vice-president, product development & strategy. Email: christine.blazynski@citeline.com.