New Drug Pipeline Monitor

June 2007

Acknowledgements

The New Drug Pipeline Monitor was prepared by the Patented Medicine Prices Review Board (PMPRB) under the provisions and conditions of the National Prescription Drug Utilization Information System (NPDUIS).

The report was produced with the invaluable assistance of the NPDUIS Steering Committee. The NPDUIS Steering Committee members for this report are:

Olaf Koester
Chair, NPDUIS Steering Committee, and Director,Drug Management Policy Unit Corporate and Provincial Program
Support Division
Manitoba Health

Dee-Jay King, Assistant Director
Pharmaceutical Policy and Programs Branch
Alberta Health and Wellness

Colleen Janes, Director
Pharmaceutical Services
Newfoundland and Labrador Department of Health and Community Services

Brett Wilmer, Senior Economist Policy Outcomes, Evaluation and Research
Pharmaceutical Services
British Columbia Ministry of Health

Patrick Crawford,
Pharmacy Services Consultant
PEI Drug Programs
Prince Edward Island Department
of Health and Social Services

Dianne Tait, Manager
Extended Benefits and
Pharmaceutical Program
Yukon Health Services

Dawn Frail, Manager
Drug Technology Assessment
Pharmaceutical Services
Nova Scotia Department of Health

Susan Pierce, Pharmaceutical Consultant
Non-Insured Health Benefits Directorate
First Nations and Inuit Health Branch
Health Canada

Hugh Ellis, Drug Policy
and Program Consultant
New Brunswick Prescription Drug Program
Department of Health

Bill Leslie, Manager
Quality Use of Medicines
Health Policy Branch
Health Canada

Tommy Cheung, Manager
Pharmaceutical Strategy
Ontario Ministry of Health
and Long Term Care

Michael Hunt, Manager
Pharmaceuticals
Canadian Institute for Health Information

Kevin Wilson, Executive Director
Drug Plan and Extended Benefits Branch
Saskatchewan Health

Christine McKennirey, Manager NPDUIS
Policy and Economic Analysis Branch
Patented Medicine Prices Review Board

The PMPRB also wishes to acknowledge the generous contribution of the Canadian Agency for Drugs and Technology in Health (CADTH) in providing both advice and information on emerging new drugs in Canada

I Introduction

This is the inaugural edition of the New Drug Pipeline Monitor (NDPM), a new web-based publication that summarizes information on new drugs that are expected to be launched in Canada within the next two to five years and could potentially have a significant impact on federal, provincial and territorial (F/P/T) drug plan expenditures.

In recent years, drug expenditures in Canada have been rising rapidly, due largely to increasing utilization and changes in the composition of drug utilization. Greater use of drug therapy instead of other forms of treatments, shifts away from older, less expensive drugs to newer, more expensive medications, as well as the use of new drug products to treat conditions for which no effective treatment existed previously, have contributed to rising drug expenditures.

The NDPM is intended to support informed decision-making by providing information on drugs which are in the latter phases of research and could have a significant impact in terms of therapeutic value. These drugs have the potential to change clinical practice, or treat a condition with no existing treatment, a life-threatening condition, or a rare disease affecting a small population.

This first edition of the NDPM describes the criteria that have been selected to identify potentially high impact investigational drugs, and the methodology used to apply these criteria. Ten new drugs in the pipeline are identified in this issue. A brief description of the drugs and their therapeutic potential is provided. Future editions will continue to track the clinical development of these drugs, and will identify other investigational drugs that meet the selected criteria. Preliminary market analyses will be provided when evidence is available.

II Criteria for drug selection

In order to identify potentially high impact new drugs that could be on the Canadian market in two to five years, criteria for selection were developed. The criteria used for selection include: phase of development, place in therapy (e.g., new approach to therapy, first to treat), specific drug characteristics (e.g., first in a class, niche target), and a preliminary assessment of efficacy (e.g., significant improvement, increased survival) and safety. A brief description of the key selection criteria follows.

i. Phase of development

Only drugs in Phase III clinical trials are considered as potential candidates for the NDPM. Most drugs reaching this stage in clinical development would have a high likelihood of proceeding to regulatory approval and marketing within the 2-5 year time period. Drugs in earlier phases of development (e.g. Phase I and II), on the other hand, may not necessarily progress beyond those stages.

ii. Indication and therapeutic area

In order to be considered as potential candidates for the NDPM, new drugs in Phase III trials are considered in conjunction with therapeutic area and indication. Drugs are considered to be potential candidates if they could be used to treat life-threatening conditions, conditions with unmet needs, or rare diseases, or if they could potentially change clinical practice in a therapeutic area.

iii. Drug description

Drug descriptions that would flag that a new drug could potentially change clinical practice include: first drug in a class, different mechanism of action, novel technology, add-on therapy, targeted niche, or existing drug with a new indication. Drugs are considered to be potential candidates for the NDPM if these descriptors apply to them.

iv. Clinical and other impacts

In order to be selected for the NDPM, drugs must demonstrate the potential to have a significant clinical impact and/or significant impact on other sectors of the health care system. Examples of potential clinical impacts include: increased efficacy vs. existing drugs; impacts on patient health (e.g. increased life expectancy or quality of life); new or redefined outcome measures; and, an improved safety profile vs. existing drugs. Examples of potential impacts on the health care system include: changes in therapeutic monitoring requirements; specialized administration requirements; and, changes in hospitalization rates.

III Methodology for applying criteria

The main source of information for the NDPM is the Biopharm Insight database which tracks drugs from pre-clinical discovery through clinical trials to market launch and subsequent sales. The database is a comprehensive resource on investigational drugs and, at any one time, may contain more than 21,000 drugs. The database search capabilities allow drugs to be selected under various headings, including: phase of development, therapeutic area, indication, drug mechanism, orphan drug, fast track, and molecule type.

An algorithm, developed for selecting drugs for the NDPM, is illustrated in Figure 1. The algorithm combines the search capabilities of the BioPharm Insight database and the key criteria used to identify a potentially high impact drug. Because the sources of information for this database are largely from the US, additional Canadian information sources are used to determine whether the new drugs are in development in Canada.

• As a first step in identifying potential candidates for the NDPM, the BioPharm Insight database is searched for drugs currently in Phase III development. Phase III trials may have just been initiated for these drugs, or some Phase III results may be available.

• Drugs in Phase III development are then screened by therapeutic area and indication. Drugs are considered as potential candidates for the NDPM if they have been identified by the US Food and Drug Administration (FDA) as orphan drugs (that treat a rare disease) or fast track drugs. The FDA considers drugs for fast track development if they are intended to treat serious or life-threatening conditions or if they demonstrate the potential to address unmet medical needs.

• For drugs that are neither fast tracked nor designated as orphan drugs, the drug profiles are searched for keywords relating to specific drug descriptions, e.g. first in class, different mechanism, novel technology, add-on therapy, targeted niche, or existing drug with a new indication, etc. If the drugs have these key descriptors, Phase III results are scanned to further validate the drug characteristics identified in the profile, e.g., significantly increased efficacy, increased safety, etc.

• At this point, drugs just entering Phase III trials are screened out, since there is insufficient information on these drugs to make a scientific assessment. However, these drugs will be tracked and assessed for future editions of the NDPM as potential candidates.

• Canadian information sources are consulted to determine whether there is information on any Canadian development. The main source of information is Pharmacy Practice which publishes, on a yearly basis, a list of promising new drugs in the later stages of development (Phase III or beyond) in Canada.

• The next step in identifying potential drugs for the NDPM involves the scientific assessment of all drugs for which preliminary Phase III results suggested an efficacy/safety impact. Details of Phase III results from the BioPharm Insight drug profiles are reviewed, particularly with regard to efficacy and safety outcomes. These reviews are supplemented by a review of the published literature.

• Finally, to confirm the selection of new drugs for the NDPM, consideration was given to the likelihood of coverage by the F/P/T public drug plans, based on indication and form. New Drug Pipeline Monitor

IV Selection of pipeline drugs for 1st edition

For this first edition of the NDPM, drugs that have recently been filed with the FDA for a New Drug Application (NDA) or a Biologic License Application (BLA), but have not yet been filed in Canada, were considered as potential candidates, along with all drugs with some Phase III results. It is expected that these drugs would be launched in Canada within the two to five year timeframe established for the NDPM.

Results of the selection process are presented in Table 1. Over 1500 drugs currently in Phase III development or recently filed with the FDA were initially considered as candidates for the NDPM. This group was reduced to 178 drugs that had descriptors described in the algorithm or were designated as orphan or fast track drugs. 61 of these drugs had preliminary Phase III results that suggested an efficacy/safety impact on the therapy of the disease. Following a scientific assessment of this group of drugs, 10 new drugs in the pipeline were identified as potentially high impact drugs and were selected for the NDPM.

Table 1 – Results of the drug selection process

The drugs highlighted in this edition of the NDPM are presented in Table 2. These drugs have several features in common. Most are new classes of drugs with different mechanisms of action, thereby representing a new approach to the specific disease management. While this has the potential to change clinical practice, the results of ongoing Phase III trials will be important to follow.

Five of the drugs selected for this edition are cancer drugs. There are different jurisdictional approaches to funding cancer drugs and these drugs may not have an impact on all F/P/T drug plans. However, these drugs will potentially have a significant impact in terms of cost or therapeutic value.

Table 2 – New pipeline drugs

1. The Biopharm Insight database provides information on whether a drug is currently in Phase III trials or whether it is under review by the FDA or the EMEA (European Medicines Agency). “In development in Canada” means that a drug company has provided confirmation via a survey published in Pharmacy Practice that clinical trials are planned or ongoing for Canada. The drug has not yet been submitted to Health Canada for approval.

V Future editions

Future editions of the NDPM will track the clinical development of the drugs that appear in this edition, and will highlight potential new drugs. It is anticipated that, over time, some of these drugs will fall off the list. Reasons for this could include the development of serious adverse effects that outweigh potential benefits.

The NDPM is intended to complement other horizon scanning activities. For example, the Canadian Agency for Drugs and Technology in Health (CADTH) publishes the Emerging Drug List, an online series that profiles new drugs and vaccines while they are at an early stage of development, prior to Health Canada approval. CADTH is developing a new drug tracking database and this database will be used in the future as a resource for the NDPM.

It is difficult to predict new drug trends with complete accuracy. The methodology used to identify drugs for the NDPM provides a systematic approach to screening new drugs and to identifying candidates that could potentially impact drug trends. To ensure that the tracking of the new drugs is as useful as possible, the selection criteria and methodology will be evaluated periodically to determine if they are appropriate and reliable.

Future editions will also provide preliminary market analyses to inform decision makers of potential cost impacts of new drugs. Sources of information on disease incidence and prevalence will be identified and these information sources will assist in defining target populations. A methodology to estimate potential cost impacts will be developed and analyses will be conducted as pricing information becomes available.