New Drug Pipeline Monitor, 6th edition – December 2014

ISSN 2292-3136
Catalogue number: H79-5/2015E - PDF

Executive Summary

The New Drug Pipeline Monitor (NDPM) provides information on drugs currently under development that may have an impact on future drug plan expenditures in Canada. This publication contains a select list of pipeline drugs that are in Phase III clinical trials or under review by the US Food and Drug Administration (FDA) and that demonstrate the potential to have a significant clinical impact.

The BioPharm Insight^® database is the main data source for this drug selection.

This is the sixth edition of the NDPM, and it updates the pipeline list reported in the December 2013 edition. This report provides an update on the 31 drugs previously identified in the pipeline and identifies 10 additions to the list.

Key Findings

1. Of the 31 pipeline drugs carried forward from the previous NDPM editions:
   • 17 are retained in this edition of the NDPM, as they continue to satisfy the criteria for drug selection, 6 of which are biologics;
   • 7 have been excluded from the list following an updated scientific assessment;
   • 4 have been excluded as they are no longer in the Phase III clinical trials in the US or under review by the FDA, and are not yet approved in Canada; and
   • 3 are removed following the granting of market authorization by Health Canada.
2. This edition of the NDPM identifies 10 pipelines drugs, 3 of which are biologics.
3. The current pipeline list features a total of 27 pipeline drugs that may have an impact on drug plan expenditures in Canada, 9 of which are biologics.

About the PMPRB

The Patented Medicine Prices Review Board (PMPRB) is an independent quasi-judicial body established by Parliament in 1987.

The PMPRB has a dual role: to ensure that prices at which patentees sell their patented medicines in Canada are not excessive; and to report on pharmaceutical trends of all medicines and R&D spending by patentees.

The PMPRB reports annually to Parliament, through the Minister of Health, on its activities, on pharmaceutical trends relating to all medicines, and on R&D spending by patentees.

The NPDUIS Initiative

The National Prescription Drug Utilization Information System (NPDUIS) provides critical analyses of drug price, utilization, and cost trends in Canada to support drug plan policy decision-making for participating federal, provincial, and territorial governments.

The NPDUIS initiative is a partnership between the PMPRB and the Canadian Institute for Health Information. It was established in 2001 by the federal, provincial and territorial Ministers of Health.

Acknowledgements

The PMPRB would like to acknowledge the contributions of:

• The members of the NPDUIS Advisory Committee, for their expert oversight and guidance in the preparation of this report
• The PMPRB NPDUIS staff for their contribution to the analytical content of the report:
  • Greg McComb – Senior Economic Analyst
  • Elena Lungu – Manager, NPDUIS
  • Branka Pejcic-Karapetrovic – Pharmaceutical Analyst
  • The PMPRB scientific and editing groups
• Patricia Carruthers-Czyzewski, BScPhm, MSc, Sintera Inc., for providing pharmaceutical expertise in the development of the methodology and the scientific input of the report

Disclaimer

NPDUIS is a research initiative that operates independently of the regulatory activities of the Board of the PMPRB. The statements and opinions expressed in this NPDUIS report do not represent the official position of the PMPRB.

Parts of this study are based on information obtained from the BioPharm Insight^® database, published by © Infinata. The analyses, conclusions and/or statements in this NPDUIS report do not represent the position of © Infinata.

1. Introduction 

This is the sixth edition of the New Drug Pipeline Monitor (NDPM), a publication that provides information on drugs currently under development that may have an impact on future drug plan expenditures in Canada. Each report contains a list of pipeline drugs identified as part of a search of the BioPharm Insight^® database^{Footnote 1}; a specialized database that provides information on over 21,000 drugs in clinical trials. The search is supported by a review of pharmacy literature, with a focus on Canadian studies.

Only drugs that meet a set of selection criteria are candidates for the NDPM. The selection criteria were prepared by Sintera Inc. for the PMPRB and were approved by the NPDUIS Advisory Committee in 2006.^{Footnote 2} This standardized approach has been consistently applied to all editions of the NDPM. The criteria include: the phase of development, the indication, the mechanism of action and the impact on clinical practice. A decision-tree algorithm was developed to ensure a consistent application of the criteria. The selection of pipeline drugs includes broad representation across therapeutic areas. In addition, consideration is given to high-cost drugs and classes where a new drug could have a financial impact on budgets, along with classes with a high utilization share of generic drugs.

As in previous reports, this edition of the NDPM updates the status of pipeline drugs identified in prior publications. Some drugs were removed from the list either because they received authority to market the drug in Canada or because a scientific assessment no longer supports retention on the pipeline list. Similarly, drugs were retained if ongoing trials supported the initial assessment for inclusion in the pipeline list.

The report is organized into seven sections. Following this Introduction, Section 2 provides an overview of the criteria used for drug selection, while Section 3 describes the algorithm used to apply the criteria. Section 4 discusses the BioPharm Insight^® database search and literature review, while section 5 provides a list of the new pipeline drugs identified for this report. Section 6 provides status updates of the pipeline drugs identified in previous reports, while Section 7 reviews the past and current pipeline drugs.

2. Criteria for Drug Selection

This section provides a brief description of the criteria developed for selecting drugs in the pipeline.

2.1 Phase of Development

Only drugs in Phase III clinical trials or under review by the US FDA are considered as potential candidates for the NDPM. Most drugs reaching this stage are more likely to proceed to regulatory approval and marketing in the near future in Canada. Drugs in earlier phases of development may not necessarily progress beyond these stages.

2.2 Indication and Therapeutic Area

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.

2.3 Drug Description

Drug description keywords that 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 an existing drug with a new indication.

2.4 Clinical and Other Impacts

Drugs must demonstrate the potential to have a significant clinical impact or a significant impact on other sectors of the health care system. Examples include: increased efficacy versus existing drugs; impacts on patient health, such as increased life expectancy or quality of life; new or redefined outcomes; or an improved safety profile. 

3. Methodology for Drug Selection

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 fields, including phase of development, therapeutic area, indication, drug mechanism, orphan drug, fast track and molecule type.

An algorithm developed for selecting drugs 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 sources are used to determine whether the new drugs are in development in Canada.

Figure 1. Algorithm for drug selection for the New Drug Pipeline Monitor*

*Figure 1 modifies the diagram presented in previous editions of the NDPM. While the algorithm has not changed, the diagram clarifies the steps taken to select drugs.

As a first step in identifying potential candidates for the NDPM, the BioPharm Insight^® database is searched for drugs currently in Phase III development or under review by the FDA, with a New Drug Application (NDA) or Biological License Application (BLA) filed. Phase III trials may have just been initiated for these drugs or some Phase III results may be available.

For the second step, 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 FDA as orphan drugs, which treat rare diseases, 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 Phase III drugs that are neither fast tracked nor designated as orphan drugs, the drug profiles are searched for keywords relating to specific drug descriptions, such as first-in-class, different mechanism, novel technology, add-on therapy, targeted niche or existing drugs with a new indication. If the drugs have these key descriptors, Phase III results are scanned to further validate the drug characteristics identified in the profile, such as a significantly increased efficacy or increased safety. At this point, drugs just entering Phase III trials are screened out, since there is insufficient information to make a scientific assessment.

In the third step, the clinical impact of each drug is considered. Canadian sources are consulted to determine whether there is information on any Canadian development. The main source of information is Pharmacy Practice, which publishes an annual list of promising new drugs in the later stages of development (Phase III or beyond) in Canada. This is followed by a scientific assessment of the identified drugs. If the preliminary Phase III results suggest an efficacy/safety impact, the drugs are then considered for inclusion in the NDPM. Finally, to confirm the selection of new drugs for the NDPM, consideration is given to the likelihood of coverage by federal, provincial, and territorial public drug plans, based on indication and formulation.

4. Drug Selection Process

The first step in identifying potential candidates for this edition of the NDPM was a search of the BioPharm Insight^® database to identify drugs currently in Phase III development or under review by the US FDA, with a NDA or BLA filed. The database search for drugs was completed on October 3, 2014, in accordance with the algorithm described in the previous section.

The BioPharm Insight^® database is updated on an ongoing basis: some data is updated every few hours, while other sections are updated weekly as the information is refreshed by the source.^{Footnote 3} Just before publication, the status of drugs in the NDPM was checked against current information in the BioPharm Insight^® database.

Table 1 summarizes, by therapeutic area, the results of this first step in the search. The database profile for each of these drugs was reviewed, with particular attention given to the drug description field. Specific keywords were sought, such as first-in-class or different mechanism. If these keywords were identified, the next step was to determine the results, if any, of Phase III clinical trials. Under the development history field of the drug profile, details of the Phase III results were scanned to further validate drug characteristics, such as increased efficacy or safety. If this scan revealed a lack of effect or a safety issue, the drug was screened out.

Based on this selection process, a total of 1,262 drugs were identified in Phase III development, and 592 drugs were identified as currently under review by the US FDA. As reported in Table 1, these drugs cover a large spectrum of therapeutic areas.

* New Drug Application/Biological License Application.

**The total reported for Phase III trials or NDA/BLA filed is not necessarily the sum of the number of drugs in each therapeutic class, as some drugs may belong to multiple therapeutic classes.

Source: BioPharm Insight^®. Note that the database search for drugs was completed as of October 3, 2014.

Table 2 reports the list of drugs from Table 1 that were further screened in as part of the second step in the selection process. Biologics are identified separately, as they tend to be high-cost drugs with the potential to impact drug plan budgets. Of the 112 drugs screened in, 38 were biologics. In most therapeutic areas, one or more biologics were identified, with the greatest number selected for cancer (11) and the immune system (5). Hormonal, infectious disease and musculoskeletal drugs each had four biologics in Phase III clinical trials and NDA/BLA filed that were retained in this second step.

* New Drug Application/Biological License Application.

Source: BioPharm Insight^®. Note that the database search for drugs was completed as of October 3, 2014.

This list was further narrowed by checking all drugs against the most recent pipeline list in Pharmacy Practice^{Footnote 4} and Health Canada’s clinical trial database^{Footnote 5} to determine whether there was information on Canadian development. The next step was a scientific assessment of this preliminary list. For this assessment, details of the Phase III results from the BioPharm drug profiles were reviewed, specifically looking for significant improvements in efficacy and safety outcomes. In addition, the MEDLINE^® database was searched to gain a sense of how the drug was viewed in the published literature.

The final screening ensured that drugs from a diverse set of therapeutic classes were included in the pipeline list. The potential financial impact on public drug plans was also taken into consideration. New drugs entering a class with high utilization (e.g., cardiovascular) or costly drugs (e.g., cancer) can be expected to increase the overall expenditure for a drug plan. The same logic can be applied to drugs entering a therapeutic area with a high utilization of generic drugs.

5. New Drugs Added to the New Drug Pipeline Monitor

Based on the drug selection process described in the previous section, 10 drugs were added to this edition of the NDPM, 3 of which are biologics. Table 3 lists these drugs, clearly identifies the ones that are biologics and provides information pertaining to the drug's trade name, company, therapeutic area and rationale for inclusion in the NDPM.

*If the drug and trade name are the same, only one entry is made.

** Companies 'working on a drug' as defined by the BioPharm Insight^® database. More than one company may develop and market a drug, and their relationship may be defined by a licensing agreement.

6. Status Update

This section provides a status update of the 31 drugs listed in the previous edition of the New Drug Pipeline Monitor for December 2013:

• 17 drugs are retained in this edition of the NDPM, as they continue to satisfy the criteria for drug selection (Section 2), see Table 4
• 7 drugs are excluded from the NDPM, as current scientific assessments of the results of the Phase III clinical trials no longer point toward the potential for the drug to have a significant clinical impact, see Table 5
• 4 drugs are removed from the NDPM, as they are no longer in Phase III clinical trials in the US or are not under the review by the US FDA, and are not yet approved in Canada, see Table 6
• 3 drugs are removed from the NDPM because they received market authorization granted by Health Canada, see Table 7

Table 4 lists the 17 drugs (including 6 biologics) from previous editions of the NDPM that remain as pipeline candidates, as they continue to satisfy the criteria for drug selection (Section 2). A status update based on a review of the BioPharm Insight^® database and recent scientific literature is provided, along with a rationale for retaining the drugs in the pipeline list. Key resources consulted include a summary of drugs in late-stage development in Canada in Pharmacy Practice,^{Footnote 24} and the Health Canada database of clinical trials in Canada^{Footnote 25}.

Table 5 lists the seven drugs from the previous edition of the New Drug Pipeline Monitor (December 2013) that are excluded from this edition, as current scientific assessments of the results of the Phase III clinical trials no longer point toward the potential for the drugs to have a significant clinical impact. At this point it is unclear whether these drugs may have an impact on drug plan expenditures in Canada.

A status update based on a review of the BioPharm Insight^® database and recent scientific literature is provided, along with a rationale for excluding the drugs from the pipeline list. Reasons for removal relate to discontinuation of clinical trials for safety and/or efficacy reasons.

Table 6 lists the four drugs from the previous edition of the New Drug Pipeline Monitor (December 2013) that are removed in this edition, as they are not currently in the Phase III clinical trials in the US or are not under the review by the US FDA, and are not yet approved in Canada. These drugs may receive market authorization in Canada in the future, and at that point they may have an impact on drug plan expenditures. A rational for the removal of the drugs from the list is provided in the table.

Table 7 reports the three drugs (including one biologic) from the previous edition of the New Drug Pipeline Monitor (December 2013) that are removed from this edition, as they have received market authorization granted by Health Canada. The Notice of Compliance (NOC) date issued by Health Canada, as well as the date of first sale, are provided in the table.

This table also includes information on recommendations made by the Common Drug Review (CDR). The CDR conducts reviews of the clinical effectiveness and cost-effectiveness of drugs, as well as reviews of patient input for drugs and provides formulary listing recommendations to public drug plans. The CDR is part of the Canadian Agency for Drugs and Technologies in Health (CADTH).

This table also reports on the status of the price review of the Patented Medicine Prices Review Board (PMPRB) for the new drugs. The PMPRB ensures that the prices of patented medicines sold in Canada are not excessive by reviewing the prices that patentees charge for each individual patented drug product to wholesalers, hospitals and pharmacies. Once the review is completed, the drug may be found to (i) be priced within the PMPRB Guidelines, (ii) exceed the Guidelines by an amount that does not trigger the investigation criteria or (iii) exceed the Guidelines and become subject to an investigation.

*A Notice of Compliance issued by Health Canada indicates that the drug product meets the regulatory requirements for use in humans or animals and that the product is approved for sale in Canada.

**The date of first sale is as reported to the PMPRB. This date may precede the Health Canada NOC date, as a product may be sold under the Special Access Programme or the Clinical Trial Applications or it may be an Investigational New Drug.

†CDR recommendations are made by the Canadian Drug Expert Committee (CDEC), an independent advisory body composed of individuals with expertise in drug therapy and drug evaluation. Submissions by manufacturers are voluntary, so recommendations may not be available for some drugs. The information on the current CDR status is available at: http://www.cadth.ca/en/products/cdr/.

7. Review of past and current NDPM drugs

To date, a total of 61 new drugs have been selected in six NDPM reports, published since 2007. At the time of inclusion in the NDPM, these drugs were either in Phase III clinical trials or under review by the US FDA and demonstrated the potential to have a significant clinical impact. Of these:

• 10 (16.4%) are new drugs identified in this edition of the NDPM
• 17 (27.9%) continue to satisfy the NDPM criteria for drug selection
• 17 (27.9%) no longer satisfy the NDPM criteria for drug selection
• 17 (27.9%) subsequently received market authorization granted by Health Canada

This suggests that the majority of the NDPM drugs (72.1%) continue to have promising scientific assessments or have received market authorization by Health Canada. A relatively small proportion of the drugs (27.9%) was excluded from NDPM because (i) the scientific assessment no longer supported retention or (ii) they are no longer in the Phase III clinical trials in the US or under review by the US FDA, and are not yet approved in Canada.