2016 Clinical Trials Roundup Steady course or changing tides? 2015 Trial Starts 2016 Clinical Trials Roundup – Steady course or changing tides? Welcome to this year’s roundup where we’ll review clinical trials that initiated in 2015 to elucidate any ongoing, or new, trends within the world of pharma R&D. Here we’ll provide a high-level overview of trial activity, focused on the six major therapeutic areas (TAs) of autoimmune/inflammation, cardiovascular, CNS, infectious disease, metabolic/endocrinology, and oncology, with metrics by TA, trial phase, and disease. We’ll then zoom in on the most active industry sponsors, including a closer look at how they may (or may not be) maximizing their assets. Now, let’s take a look at the new clinical research from 2015, and see how the course of pharma R&D fared. Doro Shin, MPH Principal Analyst, Infectious & Genitourinary Diseases Manager, Thought Leadership Program 2 April 2016 © Informa UK Ltd 2016 (Unauthorized photocopying prohibited.) Rounding up the 2015 debuts Similar to years past, this annual roundup will hone in on unapproved drug3 clinical research, which comprised Approximately 4,900 Phase I-III trials started in 2015 2,769 of trials starting in 2015 (57%). Involvement across the six TAs.1 Industry sponsors2 were involved from the industry is increased as 77% of trials initiated in the majority of these trials (2934 of 4895 trials, in 2015 with an unapproved drug is linked to an 60%), particularly in autoimmune research (487 of industry sponsor (2143 of 2769 trials). Again, 668 trials, 73%). Oncology had the lowest rate and autoimmune has the largest industry participation (383 just over half of cancer trials included an industry of 424 trials, 90%) while oncology has the lowest (750 sponsor (1110 of 2080 trials). However, there was no of 1064 trials, 70%). (Figure 1) lack of activity for oncology as the therapeutic area clearly leads in absolute trial numbers and comprised Figure 2 provides a more granular look at the 42% of all initiated studies in 2015 (2080 of 4895 unapproved drug trials starting in 2015 with a trials). (Figure 1) breakdown by trial phase for each TA. Trial counts were Figure 1. Phase I-III Clinical Trials Started in 2015 by Sponsor Type and Drug Status 1200 Unapproved Drug: Non-Industry Unapproved Drug: Industry 1000 Approved Drug: Non-Industry 314 Approved Drug: Industry 800 656 600 41 Trial Count Trial 400 79 750 116 53 395 35 200 360 226 383 140 136 296 253 111 103 104 110 87 134 0 73 72 CNS Oncology InfectiousDisease Metabolic/ Autoimmune/ Cardiovascular Source: Trialtrove February 2016 Inflammation Endocrinology 1 Trial counts as of February 11, 2016 and reflects initiated trial activity publically disclosed up to the data pull date. Also, trials that include multiple indications across different therapeutic areas will be counted for each TA it targets. As such, the sum of trial counts for the six TAs will be higher than the total number of Phase I-III trials started in 2015. 2 Excludes companies developing generics as well as the generics business of any industry sponsors (i.e. Novartis’ Sandoz or Teva’s generics arm). 3 Unapproved drugs have not received regulatory approval for any indication. This excludes drugs that were approved for an initial indication, but are unapproved for additional indications in other patient populations. slightly lower for nearly all TAs in comparison to last of the smaller therapy groups, making up only 7% of year, although this could partially be attributed to an the pipeline.4 earlier data cutoff date. The exceptions were infectious Oncology trial initiations were mostly early stage disease and oncology, both of which had slightly research, with nearly 2/3 of studies in Phase I (42%) to higher trial counts for 2015 in comparison to 2014. I/II (20%). In contrast, only 9% of new cancer trials As usual, oncology continued to reign as the leading were Phase III, which is the lowest percentage across TA by far, with over twice the trials for the runner up, the TAs. The distribution of phases was generally CNS. Cardiovascular research was the least active weighted toward earlier stages of development, which with only 169 unapproved drug trials starting in is in line with the nature of clinical R&D, and Phase I 2015. These trends in trial starts by TA parallel the comprised the largest percentage of initiated trials for makeup of the R&D pipeline by therapy group, which all TAs except autoimmune. Unlike other TAs, was outlined in Ian Lloyd’s recent Pharma R&D autoimmune started an equal number of Phase I and Annual Review. Nearly a third of 2015’s drugs in II trials in 2015. Autoimmune also had the highest active development were anticancer and percentage of Phase III research (25%), so research neurologicals were close to the top, but at a distant within this TA isn’t quite as heavily concentrated in 18% of the pipeline. Cardiovascular drugs were one earlier trial phases. (Figures 2, 3b) Figure 2. Clinical Trials Started in 2015 with an Unapproved Drug Phase I Phase I/II Phase II Phase II/III Phase III Oncology (ONC) CNS Autoimmune/Inflammation (AI) Infectious Disease (ID) Metabolic/Endocrinology (MET) Cardiovascular (CV) 0 200 400 600 800 1000 1200 Source: Trialtrove February 2016 Trial Count 4 The Pharmaprojects Pharma R&D Annual Review 2016, which provides a detailed review of trends in pharmaceutical R&D in 2015, is available to download for free at https://citeline.com/category/whitepapers/. 4 April 2016 © Informa UK Ltd 2016 (Unauthorized photocopying prohibited.) The distribution of phases for each TA remained showed the largest change as the proportion of early relatively consistent between 2014 and 2015, although stage research initiated in 2015 decreased by 11% from some shifts were observed. For the most part, phase 2014, while Phase II and III studies increased by 3% distributions were the same or only differed by +/- 5%. and 7%, respectively. Cardiovascular showed the second CNS’ pipeline has seemingly matured as the early stage largest change, primarily in the percentage of Phase III research that was initiated in 2014 progressed in trial initiations which decreased by 8% in 2015. In turn, development, while the balance of cardiovascular proportions increased slightly for Phase I through II/III, research has downshifted to earlier stages. CNS trials with the largest rise seen in Phase I/II. (Figure 3) Figure 3a. Distribution of Phases of Unapproved Drug Trials per Therapeutic Area in 2014 Phase I Phase I/II Phase II Phase II/III Phase III 100 7% 16% 16% 15% 1% 25% 21% 2% 2% 2% 80 1% 27% 1% 26% 25% 27% 22% 60 29% 20% 4% 5% 9% 6% 40 6% 52% % Trials Per TA Per % Trials 51% 48% 49% 20 39% 45% 0 AI CV CNS ID MET ONC Figure 3b. Distribution of Phases of Unapproved Drug Trials per Therapeutic Area in 2015 Phase I Phase I/II Phase II Phase II/III Phase III 100 9% 14% 25% 23% 21% 17% 2% 2% 80 3% 2% 1% 2% 23% 27% 25% 31% 60 29% 33% 8% 20% 7% 4% 5% 40 6% % Trials Per TA Per % Trials 53% 20 41% 45% 46% 42% 33% 0 AI CV CNS ID MET ONC Source: Trialtrove February 2016 © Informa UK Ltd 2016 (Unauthorized photocopying prohibited.) April 2016 5 When looking at trial counts for specific diseases,5 it’s diabetes, pain (nociceptive and neuropathic), and no surprise to see various cancers dominating the top HIV. Also, trial counts for hypertension and indications. In fact, all but five of the 15 diseases with dyslipidemia warrant inclusion among the top 25 the largest trial counts are in oncology. Unspecified diseases, even though cardiovascular was the least solid tumor sits at the top, largely driven by the vast active TA overall. The bulk of cardiovascular research number of Phase I trials, and non-small cell lung appears to be driven by these two indications as a cancer (NSCLC) follows. Both rankings are consistent total of 81 trials were started for hypertension and/or with prior reviews, but respiratory infection studies dyslipidemia in 2015 (6 studies included both, data climb to third place from last year’s sixth place. Other not shown), or 48% of all cardiovascular clinical common non-oncology indications include type 2 research. (Figure 4) Figure 4. Top 25 Diseases by Trial Count Unspecified Solid Tumor NSCLC Respiratory Infections Breast Cancer Non-Hodgkin's Lymphoma Type 2 Diabetes Pain (nociceptive) Acute Myelogenous Leukemia HIV Ovarian Cancer Renal Cancer Melanoma Head/Neck Cancer Colorectal Cancer Pain (neuropathic) Alzheimer's Disease Phase I Asthma Phase I/II Rheumatoid Arthritis Phase II Psoriasis Phase II/III Diabetic Complications Phase III Hypertension HCV Depression Osteoarthritis Dyslipidemia COPD 0 50 100 150 200 Source: Trialtrove February 2016 Trial Count 5Trial counts by disease represent each study that includes the specified indication, including studies that target multiple indications. As such, trials that include more than one disease will be counted for each indication. 6 April 2016 © Informa UK Ltd 2016 (Unauthorized photocopying prohibited.) Leading captains at the helm companies disclosed 15 trials starting in 2015 each (data not shown). The 20 most active companies were linked to 842 of the 2,769 unapproved drug studies, which is nearly a The balance between early and late stage research third.6 These top sponsors are presented in Figure 5 varied among this cohort of companies, but Phase I with AstraZeneca leading for the third year in a row, research comprised the largest number of trial starts for followed by Johnson & Johnson, Roche, and then the 15 of the 20 top sponsors.