New Drug Pipeline Monitor, 7th Edition – December 2015

New Drug Pipeline Monitor, 7th Edition – December 2015

ISSN: 2292-3136
Catalogue number: H79-5E-PDF
PDF version (1.42 MB)

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:
    • Branka Pejcic-Karapetrovic – Pharmaceutical Analyst
    • Greg McComb – Senior Economic Analyst
    • Tanya Potashnik – Director, Policy and Economic Analysis
    • Elena Lungu – Manager, NPDUIS
    • Carol McKinley – Communications Advisor
    • The PMPRB scientific and communication groups
  • Patricia Carruthers-Czyzewski, BScPhm, MSc, Sintera Inc., for providing pharmaceutical expertise in the development of the methodology and the scientific input to 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.

Although based in part on data obtained under license from IMS AG's MIDAS™ database, the statements, findings, conclusions, views and opinions expressed in this report are exclusively those of the PMPRB and are not attributable to IMS AG. All rights reserved.

Table of Contents

Executive Summary

The New Drug Pipeline Monitor (NDPM) provides information on drugs currently under development that may have an impact on future drug expenditures in Canada. This annual 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 seventh edition of the NDPM. It updates the pipeline list reported in the December 2014 edition and identifies additional drugs for this list, as of October 2015. This edition also includes a summary of the status of all of the drugs identified in previous editions of the NDPM along with a review of Canadian and international sales and prices of the drugs that have subsequently been granted market authorization in Canada.

Key Findings

This edition of the NDPM identifies 10 new pipeline drugs, 5 of which are biologics. Of the 27 pipeline drugs carried forward from the previous NDPM editions:

  • 16 are retained in this edition of the NDPM, as they continue to satisfy the criteria for drug selection, 4 of which are biologics;
  • 3 were removed from the list after being granted market authorization by Health Canada;
  • 2 were removed from the list following an updated scientific assessment; and
  • 6 were removed from the list as there is no information on current clinical trials in Canada.

The current pipeline list features a total of 26 drugs, 9 of which are biologics. To date, a total of 71 new drugs have been selected in the seven NDPM reports published since 2007, 20 of which subsequently received market authorization granted by Health Canada. These include the following recent top-selling and/or high-priced Canadian launches: aflibercept (Eylea, Zaltrap); ipilimumab (Yervoy); plerixafor (Mozobil); ticagrelor (Brilinta); eculizumab (Soliris); raltegravir (Isentress); and rivaroxaban (Xarelto).

Results based on data contained in the MIDAS™ database (IMS AG. All rights reserved) suggest that the sales for these drugs were higher in foreign markets than in Canada in Q4-2014. Factors that may explain this include: higher relative price levels (especially in the United States), earlier market launches and/or increased market uptake for the new drugs in foreign countries. The foreign markets analyzed are the seven that the Patented Medicine Prices Review Board considers in reviewing the prices of patented drug products (PMPRB7): France, Germany, Italy, Sweden, Switzerland, the United Kingdom and the United States.

The NDPM is an annual publication, with the next edition planned for 2016. Future editions will continue to monitor the pipeline list and identify new drugs to be featured in the NDPM.

Introduction

This is the seventh edition of the New Drug Pipeline Monitor (NDPM), an annual publication that provides information on drugs currently under development that may have an impact on future drug expenditures in Canada. Each report contains a list of pipeline drugs identified as part of a search of the BioPharm Insight® databaseFootnote 1; a specialized database that provides information on over 21,000 drugs in clinical trials. The search is supported by a review of recent scientific literature.

Only drugs that meet a set of selection criteria are candidates for the NDPM. The selection criteria were prepared by Sintera Inc. for the Patented Medicine Prices Review Board (PMPRB) and were approved by the NPDUIS Advisory Committee in 2006. 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 a 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 the manufacturer received authorization to market the drug in Canada or because a scientific assessment no longer supports their retention on the pipeline list. Similarly, drugs were retained if ongoing trials supported the initial assessment for inclusion on the pipeline list.

The report is organized into three sections. Following an overview of the methodology and process for drug selection, Section 1 identifies the new pipeline drugs added to this edition of the NDPM; Section 2 provides status updates of the pipeline drugs identified in previous editions; and Section 3 reviews the past and current pipeline drugs.

Drug Selection – Methodology and Process

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 of investigational drugs and may contain more than 21,000 drugs at any one time. 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.

Four main criteria are used for selecting drugs in the pipeline:

Phase of Development
Only drugs in Phase III clinical trials or under review by the US Food and Drug Administration (FDA) are considered as potential candidates for the NDPM. 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.

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.

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.

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.

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 United States, 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. Algorithm for drug selection for the New Drug Pipeline Monitor*

*Figure 1 modifies the diagram presented in previous editions of the NDPM, as it includes a search of drugs accepted in one or more US FDA expedited drug development programs for serious conditions.
†New Drug Application/Biologic License Application.
‡US FDA expedited drug development programs for serious conditions include: fast track designation, breakthrough therapy designation, accelerated approval pathway and priority review designation.

Figure description

This schematic drawing summarizes the three steps in the process of drug selection for the New Drug Pipeline Monitor. As fully described in the text, at the end of each step, drugs either meet the criteria and move to the next stage or are deemed to be unlikely candidates for inclusion in the report and are removed.

Step 1

As a first step in identifying potential candidates for the NDPM, the BioPharm Insight® database is searched for drugs currently in Phase III clinical trials or under review by the FDA, with a New Drug Application (NDA) or Biologic License Application (BLA) filed. As Phase III trials may have just been initiated for some of the drugs, the search is further narrowed to focus solely on drugs with available Phase III results to allow for their scientific assessment.

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 of action. 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 1,037 drugs were identified in Phase III clinical trials, and 479 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.

Table 1. Step 1 in the drug selection process:
Number of drugs in Phase III clinical trials or under review by the US Food and Drug Administration by therapeutic area
Therapeutic area In Phase III NDA/BLA* filed
Cancer 229 37
Cardiovascular 82 28
Central nervous system 92 69
Dermatology 38 17
Eye and ear 41 15
Gastrointestinal 43 39
Genitourinary 32 24
Hematological 46 30
HIV infections 9 10
Hormonal system 79 33
Immune system 80 37
Infectious diseases 101 66
Musculoskeletal 59 12
Nephrology 14 5
Pain 57 37
Respiratory 35 20
Total 1,037 479
* 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 the new drugs added to the NDPM was completed as of June 17, 2015.

Step 2

For the second step, drugs in Phase III clinical trials are screened by therapeutic area and indication. Drugs are considered as potential candidates for the NDPM if they have been accepted by the FDA in one or more of the four FDA expedited drug development programs for serious conditions: fast track designation, breakthrough therapy designation, accelerated approval and priority review designation. The FDA expedited drug development programs are intended to facilitate and expedite development and review of new drugs to address an unmet medical need in the treatment of a serious condition, including a life-threatening condition. In addition, drugs intended for the treatment of rare diseases and granted an orphan designation by the FDA are also considered as potential candidates for the NDPM.

For Phase III drugs that are neither in any of the FDA expedited drug development programs nor designated as orphan drugs, the drug profiles are searched for keywords relating to specific drug descriptions, such as first-in-class, different mechanism of action, 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.

Table 2 reports the drugs from Table 1 that were 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 expenditures. Of the 160 drugs screened in, 29 were biologics. In most therapeutic areas, one or more biologics were identified, with the greatest number selected for respiratory system (6) and central nervous system diseases (5). Similarly, for the therapeutic area of cancer, as well as cardiovascular diseases, 4 biologics in Phase III clinical trials or with a NDA/BLA filed were retained in this second step.

Table 2. Step 2 in the drug selection process:
Number of drugs by therapeutic area, pharmaceutical and biologic
Therapeutic area In Phase III NDA/BLA* filed
Pharmaceutical Biologic Pharmaceutical Biologic
Cancer 3 3 1
Cardiovascular 27 3 5 1
Central nervous system 29 5 16 0
Dermatology 2 1 2 1
Eye and ear 15 2 4 0
Gastrointestinal 6
Genitourinary 1
Hematological 3
HIV infections 2
Hormonal system 6 2
Immune system 5
Infectious diseases 1
Musculoskeletal 1 1
Nephrology
Pain 2
Respiratory 2 3 2 3
Total 75 18 56 11
Total 160

* New Drug Application/Biologic License Application.
Source: BioPharm Insight®. Note that the database search for the new drugs added to the NDPM was completed as of June 17, 2015.

Step 3

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. This is followed by a scientific assessment of the identified drugs. If the preliminary Phase III results suggest a positive efficacy/safety impact, the drugs are then considered for inclusion in the NDPM.

The list of drugs reported in Table 2 was further narrowed by checking all drugs against Health Canada’s Clinical Trials Database and the US National Institutes of Health (NIH) clinical trials registry to determine whether there was information on ongoing clinical trials in Canada. In previous editions of the NDPM, the primary source of information was the journal Pharmacy Practice, which no longer prepares a list of investigational drugs in Canada. To assess pipeline candidates that could be available in Canada, clinical trial sites information in the BioPharm Insight® database was consulted. In addition, the database of clinical trials in Canada, published on the Health Canada’s websiteFootnote 2, was used as a source for information on current clinical trials in Canada. Since Health Canada’s Clinical Trials Database lists trials that were authorized by Health Canada starting on April 1, 2013, before excluding a candidate, the clinical trials registry maintained by the NIHFootnote 3 was also consulted to confirm whether Canada was listed as an investigating site.

The next step was a scientific assessment of this preliminary list. For this assessment, details of the Phase III results from the BioPharm Insight® drug profiles were reviewed, specifically looking for significant improvements in efficacy and safety outcomes. In addition, the MEDLINE® database was searched to determine 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. New drugs entering a class with high utilization (e.g., cardiovascular) or costly drugs (e.g., cancer) are more likely to be featured in the NDPM, as these have the potential to impact drug expenditures. The same logic can be applied to drugs entering a therapeutic area with a high utilization of generic drugs.

1. New Drugs Added to the NDPM

Based on the drug selection process described in the previous section, 10 drugs were added to this edition of the NDPM, 5 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.

Table 3. Drugs added to the New Drug Pipeline Monitor
Drug
(Trade name)*
Company
Therapeutic area (ATC‡)
Indication
Rationale for inclusion in the NDPM
Cancer
Blinatumomab
(Blincyto)

Amgen Astellas BioPharma K.K.; Amgen, Inc.; Astellas Pharma Inc.; Lonza Group Ltd.; MedImmune, LLC
Cancer (L01)

Leukemia

Biologic
  • Received orphan drug designation and breakthrough therapy designation for acute lymphoblastic leukemia (ALL) and was granted accelerated approval by the FDA in December, 2014.
  • A first-in-class bispecific T-cell engager (BiTE) antibody that may have the potential to selectively direct and activate the human immune system to act against cancer cells.
  • In Phase III studies in Canada for ALL.Footnote 4
  • Has demonstrated a favourable safety profile and promising results.Footnote 5
  • Administered intravenously.
Nivolumab§
(Opdivo)

Bristol-Myers Squibb; Celgene Corporation; Celldex Therapeutics; Kyowa Hakko Kirin Pharma, Inc.; Novartis AG; Ono Pharmaceutical Co., Ltd.
Cancer (L01)

Melanoma

Biologic
  • Received orphan drug designation and breakthrough therapy designation for melanoma and was granted accelerated approval by the FDA in December 2014; in March 2015, the FDA approved its use for squamous non-small cell lung cancer (NSCLC).
  • A programmed death-1 (PD-1) immune checkpoint inhibitor.
  • In Phase III studies in Canada for various cancers, including melanoma.Footnote 6
  • “Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor. Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need.”Footnote 7
  • Administered intravenously.
Olaparib
(Lynparza)

AstraZeneca PLC
Cancer (L01)

Ovarian cancer
  • Received accelerated approval by the FDA in December 2014.Footnote 8
  • A poly (ADP-ribose) polymerase (PARP) inhibitor and the first drug in its class approved in the US as a monotherapy for patients with gBRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.Footnote 9 The FDA also approved a test called BRACAnalysis CDx specifically to identify women who may be candidates for treatment with Lynparza.
  • The first 'personalized' therapy for patients with BRCA mutation-positive ovarian cancer.Footnote 10
  • In Phase III studies in Canada for breast cancerFootnote 11, ovarian cancerFootnote 12,Footnote 13,Footnote 14, pancreatic cancerFootnote 15 and prostate cancer.Footnote 16
  • “Lynparza is an example of how a greater understanding of the underlying mechanisms of disease can lead to targeted, more personalized treatment.”Footnote 17
  • Administered orally.
Palbociclib
(Ibrance)

Onyx Pharmaceuticals, Inc.; Pfizer, Inc.
Cancer (L01)

Breast cancer
  • Received FDA breakthrough therapy designation in April 2013, priority review designation in October 2014, and was granted FDA accelerated approval in February 2015.
  • Selective inhibitor of cyclin-dependent kinase 4/6 (CDK4/6).
  • Add-on drug: for use with letrozole (aromatase inhibitor).
  • In Phase III studies in Canada for breast cancer.Footnote 18
  • When palbociclib was combined with letrozole, patients experienced a significantly longer progression-free survival period (20.2 months) vs. patients who received letrozole alone (10.2 months).Footnote 19
  • Administered orally.
Cardiovascular
Alirocumab
(Praluent)

Regeneron Pharmaceuticals, Inc.; Sanofi
Cardiovascular

Hypercholesterolemia

Biologic
  • Accepted for a priority review by FDA and approved in July 2015 as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C).
  • Ongoing trials, with results expected in 2017, are assessing cardiovascular outcomes and will provide a robust assessment of its long-term safety and efficacy profile.
  • First-in-class of monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) and have a significant role in the regulation of LDL-C.
  • In clinical studies in Canada.Footnote 20
  • Adding alirocumab to atorvastatin provided significantly greater low-density lipoprotein cholesterol (LDL-C) reductions vs. adding ezetimibe, doubling atorvastatin dose, or switching to rosuvastatin, and enabled greater LDL-C goal achievement.Footnote 21,Footnote 22
  • Administered subcutaneously.
Central nervous system
Valbenazine
(NBI-98854)

Mitsubishi Tanabe Pharma Corporation; Neurocrine Biosciences, Inc.
Central nervous system

Tardive dyskinesia
  • Received breakthrough therapy designation by FDA in October 2014.Footnote 23
  • Highly-selective, vesicular monoamine transporter 2 (VMAT2) inhibitor that modulates dopamine release.
  • In Phase III studies in Canada for tardive dyskinesia.Footnote 24
  • “The profound response in this Kinect 2 study demonstrates the potential of NBI-98854 as both a safe and highly effective treatment for patients suffering from tardive dyskinesia.”Footnote 25
  • Administered orally.
Hematological
Idarucizumab
(Praxbind)

Boehringer Ingelheim GmbH
Hematological, Various (V03)

Coagulant

Biologic
  • Received breakthrough therapy designation by FDA in June 2014 and was granted accelerated approval in October 2015Footnote 26; filed with European Medicines Agency (EMA) and Health Canada.Footnote 27
  • Humanized antibody fragment for use as a specific antidote for the anticoagulant effect of dabigatran.
  • In Phase III studies in Canada for uncontrolled bleeding.Footnote 28
  • Administered intravenously.
Infections
Solithromycin

Cempra Pharmaceuticals, Inc.; Merck & Co., Inc.; Toyama Chemical Company Co. Ltd.
Infectious diseases

Community-acquired pneumonia
  • Filing with FDA expected mid-2016 for community-acquired bacterial pneumonia.Footnote 29
  • A next-generation macrolide and first fluoroketolide with high potency against Gram-positive and Gram-negative bacteria commonly associated with community-acquired respiratory tract infections and skin and skin structure infections.
  • In Phase III studies in Canada for pneumonia.Footnote 30
  • Shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors.Footnote 31
  • Administered orally and intravenously.
Respiratory
Mepolizumab
(Nucala)

GlaxoSmithKline
Respiratory, Immune system (L04)

Asthma

Biologic
  • Approved by FDA in November 2015 for add-on maintenance treatment of severe eosinophilic asthma.
  • A humanized monoclonal antibody that blocks interleukin-5 and reduces inflammatory mediators-producing white blood cell accumulation in the lungs.
  • In clinical studies in Canada for asthma.Footnote 32
  • A potentially important and well tolerated therapy in carefully selected populations of patients with asthma.Footnote 33
  • Clinically significant reductions of asthma exacerbations with improvements in markers of asthma control.Footnote 34
  • Administered subcutaneously and intravenously.
Miscellaneous
Lumacaftor/Ivacaftor combination
(Orkambi)

Vertex Pharmaceuticals, Inc.
Genetic diseases, Respiratory (R07)

Cystic fibrosis (CF)
  • Received breakthrough therapy designation and orphan drug designation by FDA; approved by FDA in July 2015; has been submitted for approval by Health Canada.Footnote 35
  • Lumacaftor is a CF transmembrane conductance regulator (CFTR) corrector, designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del CFTR. Ivacaftor is a CFTR potentiator (approved in Canada in 2012 as Kalydeco) designed to enhance the function of the CFTR protein once it reaches the cell surface.
  • The first medicine designed to treat the underlying cause of cystic fibrosis in people who are homozygous for the F508del mutation in the CFTR gene (i.e., with two copies of the F508del mutation in the CFTR gene), the most common form of the disease.
  • In Phase III studies in Canada for cystic fibrosis.Footnote 36
  • The rate of pulmonary exacerbations was 30–39% lower in combination groups than in the placebo group; the rate of events leading to hospitalization or the use of intravenous antibiotics was lower in the lumacaftor–ivacaftor groups as well.Footnote 37
  • Administered orally.
* 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.
‡ When listed in the WHO ATC/DDD Index.
§ Nivolumab was approved by Health Canada on September 25, 2015.
Source: BioPharm Insight®. Note that the database search for the new drugs added to the NDPM was completed as of June 17, 2015.

2. Status Update of Current NDPM Drugs

The previous edition of the NDPM (December 2014) featured a total of 27 pipeline drugs. This edition provides a status report for these drugs, as follows:

  • 16 drugs are retained in this edition of the NDPM, as they continue to satisfy the criteria for drug selection, see Table 4;
  • 3 drugs were removed from the NDPM, after being granted market authorization by Health Canada, see Table 5;
  • 2 drugs were removed from the NDPM, as current scientific assessments of the results of the Phase III clinical trials no longer support the potential for the drug to have a significant clinical impact, see Appendix A;
  • 6 drugs were removed from the NDPM, as confirmation of current clinical trials in Canada could not be obtained, see Appendix B.

Table 4 lists the 16 drugs (including 4 biologics) from previous editions of the NDPM that remain as pipeline candidates, as they continue to satisfy the criteria for drug selection. 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. Other key resources consulted include Health Canada’s Clinical Trials Database and the US National Institutes of Health (NIH) clinical trials registry.

Table 4. Drugs retained in the New Drug Pipeline Monitor
Drug*
(Trade name)†
Company‡
Therapeutic area (ATC*)
Indication
Update and rationale for retaining in the pipeline list
ABT-199 (see Venetoclax below) Blank Blank
Ataluren
(Translarna)

Genzyme Corporation, a Sanofi Company; PTC Therapeutics, Inc.; Sanofi
Genetic diseases,
Musculoskeletal system (M09)

Cystic fibrosis; Duchenne muscular dystrophy
Previous description:
  • “Correction of the underlying gene effect is a particularly exciting prospect as a new therapy for cystic fibrosis.”Footnote 38
  • Approved conditionally in Europe in July 2014 for Duchenne muscular dystrophy.Footnote 39
  • In Phase III studies in Canada for cystic fibrosisFootnote 40 and Duchenne muscular dystrophy.Footnote 41,Footnote 42
Update:
  • Received orphan drug designation by the FDA in December 2014 for treatment of mucopolysaccharidosis type I. Previously granted FDA orphan drug designations for the following indications: cystic fibrosis resulting from a nonsense mutation (September 2004), Duchenne muscular dystrophy (January 2005), spinal muscular atrophy (March 2008).
Rationale: Current literature continues to suggest that ataluren is an important new therapy for cystic fibrosis and muscular dystrophy.
Avatrombopag
(also known as E5501)

Eisai Co., Ltd.
Hematological

Thrombocytopenia
Previous description:
  • An oral, second-generation thrombopoietin receptor agonist that stimulates platelet production.
Update:
  • There is no new published data.
  • Listed in Health Canada’s Clinical Trials Database.Footnote 43, Footnote 44
Rationale: Phase III studies are ongoing for avathrombopag as a treatment for thrombocytopenia and available information does not suggest any issues.
Betrixaban

Lee's Pharmaceutical Holdings Limited; Merck & Co., Inc.; Millennium Pharmaceuticals, Inc.; Portola Pharmaceuticals Inc.
Cardiovascular

Stroke, thrombosis
Previous description:
  • An oral, highly selective factor Xa inhibitor anticoagulant with distinct pharmacological characteristics, that offers convenience of once daily dosing, less drug interactions and may allow greater flexibility for use in patients with poor renal function.
  • Not listed in Health Canada’s Clinical Trials Database, but Canada is listed as one of the investigating sites for study NCT00742859, a phase II study.Footnote 45
Update:
  • The ongoing Phase III APEX Study is assessing betrixaban for both hospital and post-discharge prevention of venous thromboembolism, or blood clots, in acute medically ill patients. Preliminary data on efficacy trends and safety are positive.Footnote 46
Rationale: Current literature continues to suggest that betrixaban may be an effective anticoagulant.
Istradefylline
(Nouriast)

Kyowa Hakko Kirin Pharma, Inc.; Valeant Pharmaceuticals International, Inc.
Central nervous system

Parkinson's disease
Previous description:
  • First in a new class: selective adenosine A2A receptor antagonists.
  • Data obtained from seven randomized controlled trials, including 2,205 patients, showed significant reductions in the daily off-time (primary outcome).Footnote 47
  • In Phase III studies in Canada for Parkinson’s disease.Footnote 48
Update:
  • A Phase III study of 308 patients showed that istradefylline treatment was well tolerated and produced a sustained reduction in off-time in levodopa-treated Parkinson’s disease patients over a 52-week period.Footnote 49
Rationale: Current literature continues to suggest that istradefylline may be a promising non-dopaminergic therapy for the treatment of Parkinson’s disease.
Ixekizumab

Eli Lilly & Co.
Dermatology

Psoriasis

Biologic
Previous description:
  • Interleukin-17A (IL-17A) inhibitor that represents a new therapeutic approach for patients with psoriasis.
Update:
  • Results from Phase III studies show greater efficacy of ixekizumab compared to etanercept, both given as a subcutaneous injection.Footnote 50
  • In Phase III studies in Canada for plaque psoriasisFootnote 51, Footnote 52 and ankylosing spondylitis.Footnote 53
Rationale: Current literature continues to suggest that ixekizumab is an effective treatment for patients with psoriasis.
Laquinimod
(Nerventra)

Active Biotech AB; Teva
Pharmaceutical Industries Ltd.
Central nervous system (N07)

Multiple sclerosis; Crohn’s disease; Huntington’s disease; lupus nephritis
Previous description:
  • Novel once-daily, orally administered immunomodulatory compound with a favourable risk–benefit profile.Footnote 54
  • Phase II study in Crohn’s has been published.Footnote 55
Update: Rationale: Current literature continues to suggest that laquinimod may be a promising therapy for the treatment of relapsing–remitting multiple sclerosis and for Crohn’s disease.
Lebrikizumab

Chugai Pharmaceutical
Co., Ltd.; Genentech, Inc.;
Roche
Respiratory

Asthma

Biologic
Previous description:
  • An anti-IL-13 monoclonal antibody for the treatment of asthma that demonstrates benefits in patients with poorly controlled asthma.
  • In Phase III studies in Canada.Footnote 61, Footnote 62, Footnote 63
Update:
  • Data from two randomised placebo-controlled studies “extend, previously published results demonstrating the efficacy of lebrikizumab in improving rate of asthma exacerbations and lung function in patients with moderate-to-severe asthma who remain uncontrolled despite current standard-of-care treatment.”Footnote 64
  • It was granted orphan designation by FDA (March 2015) for treatment of idiopathic pulmonary fibrosis.
Rationale: Current literature continues to suggest that lebrikizumab may be a promising therapy for the treatment of asthma and other indications are also being explored.
Mipomersen
(Kynamro)

Genzyme Corporation, a Sanofi Company; Isis Pharmaceuticals, Inc.
Cardiovascular (C10)

Hypercholesterolemia
Previous description:
  • An injectable (via subcutaneous route) second-generation 2'-O-methoxyethyl chimeric antisense oligonucleotide that reduces hepatic production of apolipoprotein B-100 (Apo B), the principal apolipoprotein of LDL and its metabolic precursor, VLDL, and is “effective for lowering Apo B-containing lipoproteins in patients with severe hypercholesterolemia.”Footnote 65
  • Approved in the US in 2013 for homozygous familial hypercholesterolemia (as an orphan indication).
  • Not listed in Health Canada’s Clinical Trials Database, but Canada is listed as one of the investigating sites for study NCT00607373, a Phase III study.Footnote 66
Update:
  • In a meta-analysis of all published randomized controlled trials comparing safety and efficacy of mipomersen with placebo in adults with dyslipidemia, “mipomersen resulted in a significant improvement in lipid parameters except for HDL-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo.”Footnote 67
Rationale:Current literature continues to suggest that mipomersen may be an effective therapy for the treatment of hypercholesterolemia.
Ocrelizumab

Biogen Idec Inc.; Genentech, Inc.; Roche Holdings AG
Musculoskeletal, Immune system

Multiple sclerosis (MS)

Biologic
Previous description:
  • A humanized monoclonal antibody that selectively targets the CD20-positive B-cells implicated in the inflammatory and neurodegenerative processes of MS.
Update:
  • Results from two Phase III studies involving 1,656 relapsing MS patients (both relapsing–remitting and secondary progressive) randomized to either an ocrelizumab infusion every 6 months (600 mg) or Rebif 44 mcg three times a week showed that ocrelizumab significantly reduced relapse rates, new lesion formation on MRI and disability progression during the two years of the study compared to Rebif. A Phase III study of ocrelizumab in primary progressive MS is still underway.Footnote 68
  • Regulatory submissions in the US and Europe planned for early 2016.Footnote 69
  • Not listed in Health Canada’s Clinical Trials Database but Canada is listed as one of the investigating sites for study NCT01412333, a Phase III study.Footnote 70
Rationale: Current literature continues to suggest that ocrelizumab may be an effective treatment for multiple sclerosis.
Ponesimod

Actelion Pharmaceuticals Ltd; Roche
Immune system

Multiple sclerosis (MS) and psoriasis
Previous description:
  • Belongs to the class of sphingosine-1-phosphate receptor 1 (S1P1) modulators.
  • Potential for once-a-day oral dosing, for multiple autoimmune disorders.Footnote 71
  • “Significant clinical benefit was seen [with ponesimod for treatment of psoriasis] at week 16 that increased with maintenance therapy.”Footnote 72
Update:
  • Phase III trials in MS were initiated in April 2015.Footnote 73
  • Not listed in Health Canada’s Clinical Trials Database, but Canada is listed as one of the investigating sites for study NCT02425644, a Phase III study.Footnote 74
Rationale: Although current literature is limited, ponesimod may be an important therapy for multiple sclerosis and effective for treatment of psoriasis.
Ranirestat (also known as AS3201)

Dainippon Sumitomo Pharma Co. Ltd.; Eisai Co., Ltd.; Kyorin Pharmaceutical Co., Ltd.
Pain

Diabetic neuropathy
Previous description:
  • An oral aldose reductase inhibitor (ARI) with a stronger and longer-acting inhibitory effect compared to other drugs (e.g., pregabalin (Lyrica)) used for managing diabetic neuropathy.
Update:
  • Still in Phase III trials.
  • Not listed in Health Canada’s Clinical Trials Database, but Canada is listed as one of the investigating sites for study NCT00101426, a Phase III study.Footnote 75
Rationale: There is no new published literature on ranirestat since the last update. As Phase III studies are ongoing, it is retained and will be monitored.
Safinamide
(Xadago)

Meiji Seika Pharma Co., Ltd.; Merck Serono SA; Newron Pharmaceuticals; Zambon Group
Central nervous system

Parkinson’s disease (PD), epilepsy and restless leg syndrome
Previous description:
  • An oral α-aminoamide derivative with both dopaminergic properties (highly selective and reversible inhibition of monoamine oxidase-B) and non-dopaminergic properties (selective sodium channel blockade and calcium channel modulation, with consequent inhibition of excessive glutamate release).Footnote 76
  • “In Phase III trials, safinamide has been found to be a useful adjunctive to dopamine agonists in early PD and has been shown to increase time without increasing troublesome dyskinesias when used as an adjunct to levodopa in patients with advanced PD.” Footnote 77
  • Not listed in Health Canada’s Clinical Trials Database, but Canada is listed as one of the investigating sites for study NCT00605683, a Phase III study.Footnote 78
Update:
  • Approved in Europe (February 2015) as an add-on therapy to stable-dose levodopa, alone or in combination with other PD therapies in mid- to late-stage fluctuating PD patients; it has been filed in the US.Footnote 79
Rationale: Current literature continues to suggest that safinamide may be an effective treatment for Parkinson’s disease.
Selexipag
(Uptravi)

Actelion Pharmaceuticals Ltd.; Nippon Shinyaku Co., Ltd.
Cardiovascular

Pulmonary arterial hypertension (PAH)
Previous description:
  • An oral, selective prostacyclin (PGI2) receptor (IP receptor) agonist.
  • “The Phase III trial – GRIPHON – has a clinically relevant and highly robust primary end-point of time to first morbidity/mortality event and will provide vital information on the long-term effects of selexipag in patients with PAH.” Footnote 80
  • Not listed in Health Canada’s Clinical Trials Database, but Canada is listed as one of the investigating sites for study NCT01106014, a Phase III study.Footnote 81
Update:
  • Filed in December 2014 with FDA for the treatment of pulmonary arterial hypertension.Footnote 82
Rationale: Current literature continues to suggest that selexipag may be an effective treatment for pulmonary arterial hypertension.
Tanezumab

Eli Lilly & Co.; Pfizer, Inc.
Pain

Biologic
Previous description:
  • A humanized monoclonal antibody, given by subcutaneous injection, that inhibits nerve growth factor and may have therapeutic benefit in patients with osteoarthritis (OA) who experience inadequate pain relief with nonsteroidal anti-inflammatory drugs (NSAIDs).
Update:
  • Tanezumab compared to NSAIDs and opioids showed greater efficacy in OA.Footnote 83
  • Also being evaluated in diabetic peripheral neuropathyFootnote 84 and pain from bone metastases.Footnote 85
  • In Phase III studies in Canada.Footnote 86
Rationale: Current literature continues to suggest that tanezumab may be an effective treatment for pain management of OA.
Vatalanib

Bayer AG; Novartis AG
Cancer

Colorectal cancer, pancreatic cancer
Previous description:
  • Potentially first oral tyrosine kinase inhibitor to be used long-term in combination with standard chemotherapy for the treatment of patients with metastatic colorectal cancer.
  • “Vatalanib was well tolerated as a second-line therapy and resulted in favourable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.”Footnote 87
Update:
  • Not listed in Health Canada’s Clinical Trials Database, but Canada is listed as one of the investigating sites for study NCT00056459, a Phase III study.Footnote 88
Rationale: Current literature continues to suggest that vatalanib may be an effective treatment for pancreatic cancer.
Venetoclax
(previously referred to as ABT-199)

Abbott Laboratories; AbbVie; Genentech, Inc.; Roche Holdings AG
Cancer

Leukemias
Previous description:
  • An oral selective B-cell lymphoma/leukemia 2 (BCL-2) inhibitor that is thought to impact tumour formation, tumour growth and resistance and appears to spare platelets while achieving potent antitumour activity.Footnote 89
Update:
  • Has been granted breakthrough therapy designation by the FDA for the treatment of chronic lymphocytic leukemia (CLL) in previously treated (relapsed/refractory) patients with the 17p deletion genetic mutation.Footnote 90
  • AbbVie plans to submit regulatory applications to the FDA and the European Medicines Agency (EMA) before the end of 2015.
  • In clinical trials in Canada for chronic lymphocytic leukemia.Footnote 91
Rationale: Current literature continues to suggest that venetoclax may be an effective treatment for chronic lymphocytic leukemia.
* 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.
‡ When listed in the WHO ATC/DDD Index

Table 5 reports the three drugs (including one biologic) from the previous edition of the NDPM (December 2014) that were removed from this edition because 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 (if available), are provided in the table.

This table 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 price reviews by the Patented Medicine Prices Review Board (PMPRB). 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 a 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.

Table 5. Drugs removed from the New Drug Pipeline Monitor:
Market authorization granted by Health Canada
Drug
(Trade name)
Company
Indication NOC date*
Date of first sale
Common Drug
Review (CDR)
recommendation
PMPRB review status
Albiglutide
(Eperzan)

GlaxoSmithKline Inc.
Type 2 diabetes mellitusFootnote 92

Biologic
NOC granted: 2015-07-15

Not marketed in Canada as of October 30, 2015
Not currently under review Not currently under review
Nintedanib
(Ofev)

Boehringer Ingelheim (Canada) Ltd./Ltée
Idiopathic Pulmonary FibrosisFootnote 93 NOC granted: 2015-06-25

Date of first sale: 2015-06-29
List with clinical criteria and/or conditions (October 2015) Under review
Sacubitril/valsartan
(Entresto)

Novartis Pharmaceuticals Canada Inc.
Heart failure NOC granted: 2015-10-02

Not marketed in Canada as of October 30, 2015
Under review Under review

*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/.

3. Review of Past and Current NDPM Drugs

To date, a total of 71 new drugs have been selected in seven NDPM reports published since 2007. When they were selected, 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 (14%) are new drugs identified in this edition of the NDPM;
  • 16 (23%) continue to satisfy the NDPM criteria for drug selection;
  • 25 (35%) no longer satisfy the NDPM criteria for drug selection;
  • 20 (28%) were subsequently granted market authorization by Health Canada.

The majority of the NDPM drugs (65%) continue to have promising scientific assessments (37%) or have already received market authorization by Health Canada (28%). However, a number of the drugs (35%) were removed from the NDPM either (i) because the scientific assessments no longer supported their retention or (ii) because there was no current information to indicate that these drugs were being investigated in clinical trials in Canada.

Table 6 lists the drugs that have subsequently received market authorization granted by Health Canada. Drugs with relatively high sales and/or prices are highlighted: aflibercept (Eylea, Zaltrap); ipilimumab (Yervoy); plerixafor (Mozobil); ticagrelor (Brilinta); eculizumab (Soliris); raltegravir (Isentress); and rivaroxaban (Xarelto).

The table indicates the current Common Drug Review recommendation, the PMPRB review status and the PMPRB Maximum Average Potential Price (MAPP). Using the MIDAS™ database for the fourth quarter of 2014 (Q4-2014), the table also provides an indication of the foreign price relative to the Canadian level (foreign-to-Canadian price ratio) as well as a measure of the market penetration for the molecule in Canada and in foreign markets (sales per 1 million people for the molecule).

The results suggest that the sales for the drugs with available data were higher in foreign markets than in Canada in Q4-2014. For instance, in the case of rivaroxaban (Xarelto), which is the top-selling drug in Q4-2014 amongst the 20 featured in the NDPM, the sales for 1 million people in foreign markets were $1,188,374, which were higher than the Canadian sales of $915,396. This drug, which is an antithrombotic agent (B01), was one of the earliest drugs featured in the NDPM; it received an NOC in 2008, and a subsequent recommendation from the CDR for listing with criteria/conditions.

Factors that may explain higher sales for the new drugs in foreign markets than in Canada include: higher relative price levels (especially in the United States), earlier market launches and/or increased market uptake for the new drugs in foreign countries. Higher sales in foreign markets, however, may suggest a potential for market growth in Canada.

A price analysis of the drugs with available foreign and Canadian prices in the MIDAS™ database indicates that manufacturer-level prices in foreign markets were above the Canadian levels for some of the drugs in the table. For instance, the median price for rivaroxaban (Xarelto) 20 mg film-coated tablets in foreign markets was 12% higher than in Canada, as indicated by a foreign-to-Canadian ration of 1.12.

Note that some of the drugs may be available in the countries analyzed but may not have sales and pricing information available in IMS AG’s MIDAS™ database. The results are reported only for drugs with available information in this database.

The Canadian and international prices reported in IMS AG’s MIDAS™ database are manufacturer ex-factory prices and reflect all sales to the pharmacy sector. Market spot exchange rates were used to convert foreign currency prices into their Canadian dollar equivalents.

The foreign markets analyzed are the seven that the PMPRB considers in reviewing the prices of patented drug products (PMPRB7): France, Germany, Italy, Sweden, Switzerland, the United Kingdom and the United States.

Table 6. Past drugs identified in the New Drug Pipeline Monitor with market authorization
granted by Health Canada Sales and prices in Canada and foreign* markets, Q4-2014
NDPM
Ed.
Drug
(Trade Name)
Company
ATC Therapeutic subgroup
Indication
Notice of Compliance (NOC) date /
Date of first sale
Common Drug Review (CDR) recommendation PMPRB review status PMPRB Maximum Average Potential Price
(MAPP)
Foreign-to-Canadian price ratio‡ Sales§ per 1 million people for the molecule
Canada Average in foreign markets
7th Nintedanib
(Ofev)

Boehringer Ingelheim (Canada) Ltd./Ltée
Antineoplastic agents (L01)

Idiopathic pulmonary fibrosis
NOC granted:
June 25, 2015

Date of first sale:
June 29, 2015
List with clinical criteria and/or conditions (Oct. 2015) Under review $37,607
7th Albiglutide
(Eperzan)

GlaxoSmithKline Inc.
Drugs used in diabetes (A10)

Type 2 diabetes mellitus

Biologic
NOC granted:
July 15, 2015

Not marketed in Canada as of Oct. 30, 2015
Not currently under review Not yet sold $21,253
6th Aflibercept
(Eylea)


Bayer Inc.







(Zaltrap)
Aflibercept (Eylea):
Ophthamologicals (S01)

Macular degeneration neovascular, age-related;
macular edema secondary to central retinal vein occlusion;
macular edema, diabetic

Aflibercept (Zaltrap):
Antineoplastic agents (L01)

Metastatic colorectal cancer

Biologic
Aflibercept (Eylea):
NOC granted:
Nov. 8, 2013

Date of first sale:
Dec. 23, 2013


Aflibercept (Zaltrap):
NOC granted: Feb. 12, 2014
Date of first sale: May 8, 2014
Aflibercept (Eylea):
List with conditions
(Oct. 2014)
List with clinical criteria and/or conditions (May 2015)




Aflibercept (Zaltrap):

The pan-Canadian Oncology Drug Review (pCODR) Expert Review Committee does not recommend funding aflibercept in combination with an irinotecan-fluoropyrimidine (FOLFIRI) based therapy for patients with metastatic colorectal cancer previously treated with an oxaliplatin-containing regimen (Sept. 2014)
40 mg/mL
Within Guidelines





100 mg/vial
Within Guidelines

200 mg/vial
Within Guidelines
40 mg/mL
$1,851.1629/mL





100 mg/vial
$500.0000/vial

200 mg/vial
$1,250.0000/vial
0.78
(40 mg/mL)
$260,898** $822,165††
6th Macitentan
(Opsumit)

Actelion Pharmaceuticals Ltd.
Antihypertensives (C02)

Pulmonary arterial hypertension
NOC granted:
Nov. 6, 2013

Date of first sale:
Jan. 15, 2014
List with clinical criteria and/or conditions
(Jan. 2015)
10 mg
Within
Guidelines
10 mg $128.3572/tablet 1.14 $22,917 $58,768
6th Tofacitinib
(Xeljanz)

Pfizer Canada Inc.
Immunosuppressants (L04)

Rheumatoid arthritis
NOC granted:
April 17, 2014

Date of first sale:
June 6, 2014
List with criteria/condition
(April 2015)
5 mg
Within
Guidelines
5 mg
$29.2945/tablet
1.69 $14,054 $297,356
5th Mirabegron
(Myrbetriq)

Astellas Pharma Canada Inc.
Urologicals (G04)

Overactive bladder
NOC granted:
March 6, 2013

Date of first sale: March 28, 2013
List with criteria/condition
(Nov. 2014)
50 mg
Within
Guidelines

25 mg
Within
Guidelines
50 mg
$5.4990/tablet

25 mg
$2.1510/tablet
1.09
(50 mg)
$66,988 $128,114
5th Sacubitril/valsartan
(Entresto)

Novartis Pharmaceuticals Canada Inc
Agents acting on the renin-angiotensin system (C09)

Heart failure
NOC granted:
Oct. 2, 2015

Not marketed in Canada as of Oct. 30, 2015
Under review Not currently under review
4th Pirfenidone
(Esbriet)

InterMune International AG; InterMune Canada Inc.; Hoffmann-La Roche Limited
Immunosuppressants (L04)

Idiopathic pulmonary fibrosis
NOC granted:
Oct. 1, 2012

Date of first sale:
May 31, 2012
List with criteria/condition (April 2015) 267 mg
Within
Guidelines
267 mg $15.8878/capsule $107,752
4th Retigabine or ezogabine
(Potiga)

GlaxoSmithKline Inc.
Antiepileptics (N03)

Epilepsy
NOC granted:
Oct. 18, 2012

Not marketed in Canada as of Oct. 30, 2015

Not currently under review Not yet sold $1,508
4th Ipilimumab
(Yervoy)

Bristol-Myers Squibb
Antineoplastic agents (L01)

Melanoma

Biologic
NOC granted:
Feb. 1, 2012

Date of first sale:
Nov. 7, 2011
The pan-Canadian Oncology Drug Review (pCODR) Expert Review Committee recommended funding conditional on the cost-effectiveness of ipilimumab being improved to an acceptable level (Apr. 2012) 5 mg/mL
Within Guidelines
5 mg/mL
$627.1548/mL
1.30 $279,738 $522,354
4th Plerixafor
(Mozobil)

Genzyme Canada Inc.; Sanofi Aventis Canada Inc.
Immunostimulants (L03)

Hematopoietic stem cell mobilization
NOC granted:
Dec. 8 2011

Date of first sale:
March 26, 2012
Do not list
(Sept. 2012)
20 mg/mL
Within Guidelines
20 mg/mL
$7,100.2321/mL
1.11 $25,611 $38,539
4th Telaprevir
(Incivek)

Vertex Pharmaceuticals (Canada) Incorporated
Antivirals for Systemic Use (J05)

Hepatitis C
NOC granted:
Aug.16, 2011

Date of first sale:
Oct. 3, 2011
List with criteria/conditions
(June 2013)
375 mg
Within Guidelines
375 mg
$71.7040/tablet
0.87 $16,160 $31,446
4th Ticagrelor
(Brilinta)

AstraZeneca
Antithrombotic Agents (B01)

Acute coronary syndromes
NOC granted:
May 30, 2011

Date of first sale:
June 1, 2011
Do not list (Dec. 2011) 90 mg
Within Guidelines
90 mg
$1.4377/tablet
1.07 $141,498 $202,890
4th Vandetanib
(Caprelsa)

AstraZeneca
Antineoplastic Agents (L01)

Thyroid cancer
NOC granted:
Jan.12, 2012

Date of first sale:
Feb. 23, 2012
Not currently under review 300 mg
Does Not Trigger Investigation

100 mg
Within Guidelines
300 mg
$189.4568/tablet

100 mg
$174.2366/tablet
1.25
(300 mg)
$11,906 $17,250
4th Perampanel
(Fycompa)

Eisai Ltd.
Antiepileptics (N03)

Epilepsy
NOC granted:
April 4, 2013

Date of first sale:
May 17, 2013
List with criteria/condition

(Oct. 2013)
2 mg
Within Guidelines

4 mg
Within Guidelines

6 mg
Within Guidelines

8 mg
Within Guidelines

10 mg
Within Guidelines

12 mg
Within Guidelines
2 mg
$9.4500/tablet

4 mg
$9.4500/tablet

6 mg
$9.4500/tablet

8 mg
$9.4500/tablet

10 mg
$9.4500/tablet

12 mg
$10.9300/tablet
0.73
(2 mg)
$15,237 $18,159
3rd Eculizumab
(Soliris)

Alexion Pharmaceuticals Inc.
Immunosuppressants (L04)

Paroxysmal nocturnal hemoglobinuria;
atypical hemolytic uremic syndrome

Biologic
NOC granted:
Jan 28, 2009

Date of first sale:
May 25, 2009
Do not list (Feb. 2010)
Do not list (July 2013)
Notice of Hearing $417,041
3rd Lapatinib
(Tykerb)

GlaxoSmithKline Inc.; Novartis Pharmaceuticals Canada Inc.
Antineoplastic agents (L01)

Breast cancer
NOC granted:
May 15, 2009

Date of first sale:
June 5, 2009
The pan-Canadian Oncology Drug Review (pCODR) Expert Review Committee does not recommend funding lapatinib in combination with letrozole in postmenopausal patients with hormone receptor positive, HER2 receptor positive metastatic breast cancer (July 2013) 250 mg
Within Guidelines
250 mg
$27.0664/tablet
1.03 $22,264 $52,021
3rd Raltegravir
(Isentress)

Merck Frosst Canada Ltd.
Antivirals for systemic use (J05)

HIV-1 infection
NOC granted:
Nov. 27, 2007

Date of first sale:
Nov. 28, 2007
Do not list (June 2010) 400 mg
Within Guidelines

100 mg
Within Guidelines

25 mg
Within Guidelines
400 mg
$13.5000/tablet

100 mg
$4.2033/tablet

25 mg
$1.0509/tablet
1.05
(400 mg)
$361,760 $443,287
3rd Rivaroxaban
(Xarelto)

Bayer Inc.
Antithrombotic agents (B01)

Venous thromboembolic events; stroke; systemic embolism
NOC granted:
Sept. 15, 2008

Date of first sale:
Sept.16, 2008
List with clinical criteria/conditions
(Dec. 2008)
20 mg
Within Guidelines

15 mg
Within Guidelines

10 mg
Voluntary Compliance Undertaking
20 mg
$3.2000/tablet

15 mg
$2.8400/tablet

10 mg
$8.9702/tablet
1.12
(20 mg)
$915,396 $1,188,374
3rd Sapropterin
(Kuvan)

Biomarin Pharmaceutical Inc.
Alimentary tract and metabolism products (A16)

Phenylketonuria
NOC granted:
April 30, 2010

Date of first sale:
July 5, 2010
Do not list
(Jan. 2011)
100 mg
Within Guidelines
100 mg
$34.8421/tablet
$43,319
Note: Some of the drugs may be available in the countries analyzed but may not have sales and pricing information available in IMS AG’s MIDAS™ database. The results are reported only for drugs with available information in this database.

* France, Germany, Italy, Sweden, Switzerland, the United Kingdom and the United States (PMPRB7).
NDPM edition when the drug was removed from the pipeline list as it received market authorization from Health Canada.
At manufacturer levels. Results are restricted to the retail market (excluding hospital sales) and prescription bound products.
§ In Canada, where available; otherwise, in the PMPRB7.
** Sales for Eylea. Zaltrap has no available sales in the retail market in Canada, as reported by IMS AG’s MIDAS™ database.
Sales for Eylea and Zaltrap combined.

Source: MIDAS™ database, October–December 2014, IMS AG. All rights reserved.

Appendix A: Drugs removed from the list due to scientific assessment

Table A identifies the two drugs from the previous edition of the NDPM (December 2014) that were excluded from this edition, as current scientific assessments of the results of the Phase III clinical trials no longer support the potential for a significant clinical impact.

Table A. Drugs removed from the New Drug Pipeline Monitor:
Current scientific assessment
Drug
(Trade name)
Company
Therapeutic area
Indication
Rationale for Removal
Cethromycin
(Restanza)

Advanced Life Sciences, Inc.; Pfizer, Inc.
Infections

Community-acquired pneumonia
Previous description:
  • An oral antibiotic designed to overcome emerging bacterial resistance to macrolides and penicillins in the treatment of community-acquired pneumonia.
Update:
  • “…two studies did find significantly more adverse events with use of cethromycin as compared to clarithromycin and nemonoxacin when compared to levofloxacin.”Footnote 94
NX-1207

Nymox Pharmaceutical Corporation; Recordati S.P.A.
Genitourinary

Benign prostatic hyperplasia
Previous description:
  • A first-in-class drug for the treatment of benign prostatic hyperplasia, a disorder that causes difficulties with urination associated with aging.
Update:
  • Phase III studies failed to meet primary endpoint.Footnote 95

Appendix B: Drugs removed from the list due to lack of evidence of ongoing clinical trials

Table B lists the six drugs from the previous edition of the NDPM (December 2014) that were removed in this edition, as there is no evidene that they are currently being investigated in clinical trials in Canada. Nevertheless, these drugs may receive market authorization in Canada in the future.

Table B. Drugs removed from the New Drug Pipeline Monitor: No evidence of ongoing clinical trials in Canada
Drug
(Trade name)
Company
Therapeutic area
Indication
Rationale for Removal
Cetilistat
(Cametor)

Norgine BV; Takeda

Pharmaceutical Company Limited
Gastrointestinal

Obesity
Previous description:
  • Showed similar weight loss to that seen with orlistat (Xenical) but with up to 90% fewer severe gastrointestinal side effects.Footnote 96
  • Approved in Japan (September 2013).
  • “Cetilistat showed mild to moderate adverse events, predominantly of gastrointestinal nature (steatorrhea), with an incidence lower than orlistat.”Footnote 97
Rationale for removal:
  • Not listed in Health Canada’s Clinical Trials Database. Canada’s participation could not be confirmed in trials listed on www.clinicaltrials.gov.
DIMS 0150
(Kappaproct)

InDex Pharmaceuticals AB
Immune System

Ulcerative colitis
Previous description:
  • New class: Toll-like receptor 9 (TLR9) agonist that may be an effective, non-invasive treatment option for  patients with severe ulcerative colitis who no longer respond to steroid therapy and whose only current alternative is surgical removal of the colon.
Rationale for removal:
  • Not listed in Health Canada’s Clinical Trials Database. Canada’s participation could not be confirmed in trials listed on www.clinicaltrials.gov.
Lorcaserin hydrochloride
(Belviq)

Arena Pharmaceuticals, Inc.; CY Biotech Company Ltd.; Eisai Co., Ltd.; Ildong Pharmaceutical Co., Ltd.
Gastrointestinal

Obesity
Previous description:
  • An oral, serotonin (5-hydroxy-tryptamine, 5-HT) 5-HT2C receptor agonist that regulates food intake.
  • Approved in the US in 2012.
Rationale for removal:
  • Not listed in Health Canada’s Clinical Trials Database. Canada’s participation could not be confirmed in trials listed on www.clinicaltrials.gov.
Rebamipide
(Mucosta)

Acucela, Inc.; Novartis AG; Otsuka Pharmaceutical Co., Ltd.
Eye and ear; gastrointestinal

Dry eye syndrome
Previous description:
  • An amino acid derivative of 2(1H)-quinolinone, used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis.
  • “The results of the study show that 2% rebamipide is effective in improving both the objective signs and subjective symptoms of dry eye patients for at least 52 weeks. In addition, 2% rebamipide treatment was generally well tolerated.”Footnote 98
Rationale for removal:
  • Not listed in Health Canada’s Clinical Trials Database. Canada’s participation could not be confirmed in trials listed on www.clinicaltrials.gov.
Rigosertib sodium
(Estybon)

Baxter International, Inc.; Onconova Therapeutics, Inc.; SymBio Pharmaceuticals Limited
Cancer

Solid and hematological cancers
Previous description:
  • New class: an inhibitor of the phosphoinositide 3-kinase and polo-like kinase pathways that induces mitotic arrest and apoptosis in neoplastic cells, while sparing normal cells.
Rationale for removal:
  • Not listed in Health Canada’s Clinical Trials Database. Canada’s participation could not be confirmed in trials listed on www.clinicaltrials.gov.
Sotatercept
(ACE-011)

Acceleron Pharma;

Celgene Corporation
Cancer

Anemia, bone cancer

Biologic
Previous description:
  • A protein therapeutic that increases red blood cell levels by targeting molecules in the TGF-β superfamily.
  • Potential to stimulate bone formation: unmet medical need in treatment of bone loss.
  • “Multiple doses of sotatercept plus thalidomide appear to be safe and generally well-tolerated in multiple myeloma patients.” Footnote 99
Rationale for removal:
  • Not listed in Health Canada’s Clinical Trials Database. Canada’s participation could not be confirmed in trials listed on www.clinicaltrials.gov.
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