VOI News

Cancer Drug Approval Trends 2005 - 2011

 Introduction

This is the first in a series of blog posts VOI Consulting will publish based on high-level examination of the company’s new insiteinvestigator database which contains information on design, endpoints, populations, size, placement, timelines, efficacy outcomes, and safety results for every pivotal trial supporting a cancer drug approved by the U.S. FDA from 2005 through 2011. Each article will examine a specific topic to include: cancer drug approval trends, approval requirements, pivotal trial design, size, location, and key timing elements such recruitment periods and patient accrual per site within specific cancer types.

Cancer Drug Approval Trends

From the start of 2005 through the end of 2011, 48 different drugs were approved by the FDA for 83 different indications, of which 38 were new and 45 were supplemental. One hundred pivotal trials supported these approvals, an average of 1.2 trials per indication. (Note that there is some latitude in what constitutes a pivotal trial. For our purposes, we have defined a pivotal trial as a study that was extensively relied on by the agency for approval purposes. This means extensive discussion in regulatory materials surrounding the approval and, generally, inclusion on the approved prescribing label.) As shown in Figure 1, 60% percent of approved indications were for solid tumors while the remaining 40% were for hematologic malignancies. Of 22 different conditions with approvals, leukemia, breast cancer, and Non-Hodgkin lymphoma saw the highest level of activity; together, these three cancers represented over one-third of all drugs approved during the period. Forty-one percent of all approvals had previously received orphan drug designation. Although more approvals were for solid tumors, the majority of orphan drug indications were for hematologic malignancies.

Figure 1- Cancer Drug Approvals by Cancer Type 2005-2011

The rapid advance in cancer research is clearly evident in Figure 2. As shown, traditional anti-cancer agents such as chemotherapeutics and hormonal drugs accounted for two-thirds of approvals in 2005. By 2011 this had shrunk to less than 15% as new generation treatments such as biologics, targeted oral drugs, and vaccines have come to dominate the field. Although not shown on the chart, the trend towards new generation therapies has been driven mostly by the kinase inhibitor class. The first of these therapies, imatinib, was approved just a little over ten years ago but the category, which also includes erlotinib, nilotinib, sutininib, and several others, accounted for one-third of all approved indications over our total time period and reached 50% of all approvals in 2011.


Figure 2 - Approvals by Drug Type 2005-2011

Therapeutic Cancer Vaccines Webinar

Todd Clark, President of VOI Consulting, will be participating in a webcast hosted by Clinipace Worldwide on Tuesday, December 6, 2011 at 2:00 pm EST. The webcast, “Game Plan for Therapeutic Cancer Vaccines,” will address the nuances of clinical trials in the rapidly growing field of cancer vaccines. Using findings from  VOI’s new insiteinvestigator database, Todd will be covering aspects related to the size, location, timing, and accrual of vaccines trials and how these factors compare to trials of other cancer drugs. Registration is free and can be accessed at http://clinipace.com/webcast-game-plan-for-therapeutic-cancer-vaccines.htm.

Dramatic Leap in Patient Demand for NHL Trials

With multiple drugs entering Phase III clinical trials in 2011, demand for patient enrollment in non-Hodgkin Lymphoma studies is skyrocketing. As shown in the table below, these trials include two Phase III efforts for GA101, which Roche is developing to combat the potential loss of exclusivity on current standard-of-care Rituxan in 2015; a subcutaneous version of Rituxan is also moving into Phase III trials this year. Considering both the importance of Rituxan to the Roche’s bottom line and the company’s presence in the field, one can expect highly competitive recruitment efforts for these trials. Though not shown in the table, several other products including Calistoga Pharmaceutical’s CAL-101 and Pharmacyclic’s PCI-32765 are at earlier stages of development but have generated considerable interest with new mechanisms of action in orally available form.

Drug

Company

NHL Type(s)

Regimen / Comparison

Primary Endpoint(s)

Enrollment

GA101

Roche / Genentech

Indolent, Advanced

GA101-Chemo v. Ritux-Chemo, followed by GA101 v. Ritux maintenance

PFS

1400

GA101

Roche / Genentech

DLBCL

GA101-CHOP v. Ritux-CHOP

PFS

1400

Bortezomib

Takeda-Millennium

DLBCL

Bortezomib-CHOP v. Ritux-CHOP

PFS

940

Bendamustine

Cephalon

Indolent

Bendamustine v. Investigator's Choice

PFS

125

Inotuzumab

Pfizer

DLBCL

Inotuzumab-Ritux v. Investigator's Choice

OS

377

Pixantrone

Cell Therapeutics

DLBCL

Pixantrone-Ritux v. Gemcitabine-Ritux

PFS, OS

350

Rituximab (Subcutaneous)

Roche / Genentech

Follicular

Sub-Q Ritux v. IV Ritux

PK, Response, PFS

530

All this activity will put strains on clinical trial enrollment goals for the foreseeable future. Indeed, VOI Consulting’s analysis shows that an average of 3,160 newly randomized patients will be needed in both 2012 and 2013 to fully enroll all industry-sponsored Phase II/Phase III studies trials in B-cell NHL alone. This represents a 68% increase in patient demand compared to the 2007-2010 average and does not include trials that have yet to be registered.

Data from VOI’s insiteinvestigator shows that major NHL drug trials have accrued at a little under 0.16 patients per site per month in recent years. At this rate, it will require approximately 19,750 “site months” to meet currently scheduled enrollment needs for 2012; a target that would require the industry to enlist a total of 1,645 sites worldwide within the 12-month period. Leaving aside the fact that competition will decrease average site productivity levels, this number is significantly higher than currently available infrastructure.

Now consider that at least the same number of patients will be required in 2013 and it becomes pretty clear that NHL trials are going to experience major delays. Companies in this space should be prepared for stiff competition and plan recruitment efforts and site lists accordingly.