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Pet Cancer 2019: A Developing MarketCompanies; Regulations; Therapeutics; Future Trends

Animal Pharm Pet Cancer 2019: A Developing Market Contents

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Contents

Contents ..................................................................................................................................... 1

Executive Summary .................................................................................................................... 6

Chapter 1: Introduction .............................................................................................................. 7

1.1 The Animal Health Industry....................................................................................................................... 7

1.2 The Companion Animal Sector .................................................................................................................. 8

1.2.1. Changes in Pet Ownership ............................................................................................................ 8

Pet Ownership in the USA ....................................................................................................... 9

Pet Ownership in Europe ......................................................................................................... 9

1.2.2. The Future of Companion Animal Health in Developed Markets ............................................... 10

1.3 Summary ................................................................................................................................................. 12

Chapter 2: Pet Cancer – Factors Influencing the Market ......................................................... 13

2.1 Overview ................................................................................................................................................. 13

2.2 Translation of Pet Cancer Research to Human Health ............................................................................ 13

2.3 Owner Perceptions of Cancer in their Pet ............................................................................................... 14

2.4 Factors Influencing Owners Decisions in Relation to Chemotherapy ..................................................... 14

2.5 Owners Concerns During Treatment of their Pet for Cancer .................................................................. 15

2.6 Owner Perceptions of Radiotherapy ....................................................................................................... 15

2.7 Assessment of Quality of Life in Pets Receiving Cancer Treatment ........................................................ 15

2.8 Vet Perceptions of Cancer Treatment of Pets ......................................................................................... 16

2.9 Cancer Clinical Trials................................................................................................................................ 16

2.10 A Holistic Approach ................................................................................................................................. 17

2.11 Supporting organisations ........................................................................................................................ 18

Chapter 3: The Animal Health Companies Cited in this Report ............................................... 20

Overview ............................................................................................................................................................. 20

3.1 AB Science ............................................................................................................................................... 20

3.2 Anivive Lifesciences ................................................................................................................................. 20

3.3 Aratana Therapeutics .............................................................................................................................. 21

3.4 ARK Animal Health .................................................................................................................................. 21

3.5 Assisi Research Laboratories ................................................................................................................... 22

3.6 EirGen Pharma ........................................................................................................................................ 22

3.7 Elanco ...................................................................................................................................................... 22

3.8 ELIAS Animal Health ................................................................................................................................ 23

3.9 Jaguar (Animal) Health ............................................................................................................................ 23

3.10 Karyopharm Therapeutics ....................................................................................................................... 23

3.11 Man’s Best Friends Therapeutics ............................................................................................................ 24

3.12 Merial/Boehringer Ingelheim .................................................................................................................. 24

3.13 Novavive .................................................................................................................................................. 24

3.14 Nuovo Biologics ....................................................................................................................................... 25

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3.15 Ogenx Therapeutics Corporation ............................................................................................................ 25

3.16 Oasmia Pharmaceutical ........................................................................................................................... 25

3.17 PharmAust ............................................................................................................................................... 26

3.18 QBiotics ................................................................................................................................................... 26

3.19 Rhizen Pharmaceuticals .......................................................................................................................... 26

3.20 Torigen Pharma ....................................................................................................................................... 27

3.21 Veiove Animal Health .............................................................................................................................. 27

3.22 Vet DC ..................................................................................................................................................... 27

3.23 Virbac ...................................................................................................................................................... 27

3.24 Zoetis ....................................................................................................................................................... 28

Chapter 4: Regulation of Pet Cancer Products ......................................................................... 29

4.1 The United States (US) and European (EU) Regulatory Authorities ........................................................ 29

4.2 Regulatory Guidance ............................................................................................................................... 29

4.3 Availability of Pet Cancer Medicines and Vaccines ................................................................................. 30

4.4 Use of Unlicensed Medicinal Products .................................................................................................... 33

Chapter 5: Pet Cancer - Incidence ............................................................................................ 34

5.1 Overview ................................................................................................................................................. 34

5.2 Pet Cancer Incidence ............................................................................................................................... 34

5.3 Types and Locations of Pet Cancer.......................................................................................................... 39

5.4 Overall conclusion on the incidence and prevalence of cancer in pets .................................................. 42

Chapter 6: Pet Cancer - Current Management Modalities for common tumours .................. 43

6.1 Mast Cell Tumours .................................................................................................................................. 43

6.2 Mammary tumours ................................................................................................................................. 44

6.3 Melanoma ............................................................................................................................................... 45

6.4 Lymphoma .............................................................................................................................................. 46

6.5 Injection site sarcoma/fibrosarcoma ...................................................................................................... 47

6.6 Squamous cell carcinoma ........................................................................................................................ 48

6.7 Osteosarcoma ......................................................................................................................................... 50

Chapter 7: Pet Cancer Pharmaceuticals ................................................................................... 52

7.1 Overview ................................................................................................................................................. 52

7.2 Palladia (Zoetis) ....................................................................................................................................... 52

7.3 Masivet (AB Science) ............................................................................................................................... 53

7.4 Tanovea-CA1 (VetDC) .............................................................................................................................. 54

7.5 Paccal Vet-CA1 (Oasmia) ......................................................................................................................... 55

7.6 Pet Cancer Pharmaceuticals in Development ......................................................................................... 55

Doxophos Vet (Oasmia) ......................................................................................................... 55

Tigilanol tiglate (QBiotics/Virbac) .......................................................................................... 56

Verdinexor (Anivive Lifesciences) .......................................................................................... 56

RC-2b geroxane (Ogenx Therapeutics Corporation) .............................................................. 56

Asparaginase (Assisi Research Laboratories)......................................................................... 57

Resiniferatoxin (ARK Animal Health) ..................................................................................... 57

SP-SAP: Substance P & Saporin (Veiove Animal Health) ....................................................... 57

RV1001, PI3Kδ inhibitor (Rhizen Pharmaceutical) ................................................................. 57

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Chlorambucil (EirGen Pharma) .............................................................................................. 57

Canalevia (Jaguar Animal Health) .......................................................................................... 57

Dactinomycin (Assisi Research Laboratories) ........................................................................ 58

7.7 Other Potential Pet Cancer Products ...................................................................................................... 58

Chapter 8: Pet Cancer Immunologicals .................................................................................... 59

8.1 Overview ................................................................................................................................................. 59

8.2 Oncept Canine Melanoma Vaccine DNA (Merial/Boehringer Ingelheim) ............................................... 59

8.3 Oncept IL-2 (Merial/Boehringer Ingelheim) ............................................................................................ 60

8.4 Immunocidin (Novavive) ......................................................................................................................... 61

8.5 Pet Cancer Immunotherapies in Development ....................................................................................... 62

Osteosarcoma vaccine (Aratana Therapeutics) ..................................................................... 62

Torigen Pharma ..................................................................................................................... 63

ELIAS Cancer Immunotherapy: ECI (Elias Animal Health) ...................................................... 63

Prophylactic Vaccine Project ................................................................................................. 63

Man’s Best Friends Therapeutics (MBFT) .............................................................................. 64

Summary .................................................................................................................................. 65

References ................................................................................................................................ 66

List of Figures

Figure 1: Percentage of European Households owning at least one cat or one dog....................................... 9

Figure 2: Pet age in human years .................................................................................................................. 11

Figure 3: Holistic approach ............................................................................................................................ 17

Figure 4: Feline fibrosarcoma ........................................................................................................................ 40

Figure 5: Canine mammary tumour .............................................................................................................. 41

Figure 6: Canine osteosarcoma ..................................................................................................................... 42

Figure 7: Mast Cell Tumours .......................................................................................................................... 43

Figure 8: Mammary Tumours ........................................................................................................................ 44

Figure 9: Canine Oral Melanoma ................................................................................................................... 45

Figure 10: Feline Ocular Melanoma ................................................................................................................ 46

Figure 11: Canine lymphoma ........................................................................................................................... 46

Figure 12: Feline lymphoma ............................................................................................................................ 47

Figure 13: Feline fibrosarcoma ........................................................................................................................ 48

Figure 14: Canine Squamous cell carcinoma ................................................................................................... 48

Figure 15: Feline Squamous cell carcinoma (extremities) ............................................................................... 49

Figure 16: Feline Squamous cell carcinoma (oral) ........................................................................................... 49

Figure 17: Canine Osteosarcoma ..................................................................................................................... 50

Figure 18: Feline Osteosarcoma ...................................................................................................................... 51

Figure 19: Palladia ........................................................................................................................................... 53

Figure 20: Masivet ........................................................................................................................................... 54

Figure 21: Tanovea-CA1 ................................................................................................................................... 54

Figure 22: Paccal Vet-CA-1 .............................................................................................................................. 55

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Figure 23: VET JET system ............................................................................................................................... 60

Figure 24: Oncept IL-2 ..................................................................................................................................... 61

Figure 25: Immunocidin ................................................................................................................................... 62

List of Tables

Table 1: Top ten dog and cat ownership countries in the EU in 2017 ......................................................... 10

Table 2: Anti-cancer guidelines issued by the EMA and FDA CVM .............................................................. 30

Table 3: CVM designations with a canine cancer indication ........................................................................ 31

Table 4: Summary of Veterinary Cancer Registries (Active and Dormant) .................................................. 35

Table 5: Incidence of Canine Cancer in Developed Countries ...................................................................... 37

Table 6: Incidence of Feline Cancer in Developed Countries ....................................................................... 38

Table 7: Common Anatomical Locations for Canine Cancer ........................................................................ 39

Table 8: Common Anatomical Locations for Feline Cancer .......................................................................... 40

Executive Summary Animal Pharm Pet Cancer 2019: A Developing Market

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Executive Summary

Dear Reader,

The pet market is growing at a dramatic rate with health care products and services comprising a

significant portion of the expenditure on pets. This will likely increase as pet life spans lengthen and the

pet population ages.

There has been significant growth in the prevalence of age-related pathologies such as cancer in companion

animals, creating market pressure for reformulation of current human products and the discovery of new

drugs. Cats and dogs are increasingly humanized by their ageing affluent owners, who are now prepared to

treat age-related and chronic conditions that were previously considered too costly. Simply, there are more pet

owners, they are living for longer and expect their pets to do likewise.

Increasing demand from pet owners to treat their pet’s cancer combined with leveraging human health

advances and collaborative research with universities and biotech companies has led to the development of

new therapeutic approaches and new technologies. As novel technologies challenge the current regulatory

infrastructure, the FDA and EMA have responded by issuing new guidance and encouraging innovation through

Minor Use Minor Species (MUMS) for less common indications.

Many biotech firms believe that development of pet cancer treatments is a good opportunity for the

companion animal market. The start up scene in animal health has been burgeoning, especially in the USA,

resulting in a diverse network of companies providing a new source of product innovation. This has been

encouraged by human health interest in comparative oncology which speeds up the development of

medications for human cancer patients by treating animal patients with naturally developing tumours. Many of

these companies are recognizing that animal health offers a shorter and cheaper route to the market than the

human pharma market, and that sales of an animal health product helps fund human R&D.

In conclusion, pet cancer has recently seen a huge and diverse investment in R&D, primarily by smaller firms

and not-for-profit entities with limited financial resources. However, there remains plenty of room for

innovation and success in the pet cancer treatment area, whether a product is used alongside another

treatment or as a second-line/later-stage therapy. New veterinary products, such as VetDC’s Tanovea have

recently been conditionally approved, and there are a significant number of drugs and immunotherapies

approaching conclusion of their development phases. Therefore, it is probable that more products will shortly

become commercially available to treat pet cancer. However, cancer remains a challenging disease to treat

effectively. As human health technologies advance, the animal health industry will follow. This is certainly an

interesting space to watch in the future!

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Cat ownership across Europe exceeds dog ownership (74.4 million cats vs 66.4 million dogs), although dog

ownership in the EU has increased from 63.7 million in 2016 (Table 1). The UK Pet Food Manufactures

Association estimates the population of dog and cats in the UK to be 9 million and 8 million respectively.

An average of 18% of households own a cat and an average of 26% of households own a dog

(https://www.pfma.org.uk/dog-population-2018; https://www.pfma.org.uk/cat-population-2018).

1.2.2. The Future of Companion Animal Health in Developed Markets

Growth within the developed markets will most likely be established through the following means:

1. Animal health companies will increasingly focus their sales strategy on building customer relations by

linking value added services to purchase targets rather than the mass promotions, designed to capture a

large customer base which have previously been used. Additionally, emphasising the importance of their

contribution to R & D will provide a unique selling point that differentiates them from generic

competitors.

2. The absence of novel veterinary drugs is likely to negatively impact on the predicted overall market

growth, however increasing demand particularly from pet owners, to treat conditions previously

considered not worthy of treatment such as cancer has led to the development of new therapeutic

areas and new technologies. (http://www.marketwatch.com/story/veterinary-drugs-market-to-reach-

us267-bn-by-2024-rising-inclination-toward-ensuring-health-and-wellness-of-companion-animals-to-aid-

growth-says-tmr-2017-03-10-72033126). The advancement in technology has enabled a ‘spill-over’ from

human health to animal health. Biotechnology companies are involved in developing companion animal

products for ailments usually considered of high importance in human medicine, including cancer. These

new therapeutic strategies may still hold a relatively small share of the segment but are likely to be high

value. When it was introduced in 2009, Merial’s mAbs cancer vaccine for dogs with stage II and stage III

oral melanoma was the first USDA-approved therapeutic vaccine for the treatment of cancer in either

animals or humans (https://www.lifescienceleader.com/doc/why-animal-health-is-the-next-big-growth-

area-0001?user=C89F7196-FF9D-490C-A97C-8358CE26C4FD&vm_tId=1951530)

Table 1: Top ten dog and cat ownership countries in the EU in 2017

Country Number of Dogs (million) Country Number of Cats (million)

Germany 9.20 Germany 13.70

UK 8.65 France 13.50

Poland 7.55 UK 7.90

France 7.40 Italy 7.48

Italy 6.97 Poland 6.10

Spain 6.27 Romania 4.30

Romania 4.13 Spain 3.15

Czech Republic 2.15 Netherlands 2.62

Portugal 2.05 Hungary 2.28

Hungary 2.05 Belgium 2.03

Source: FIDIAF Facts and figures, 2017

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Many factors influence a pet owner’s decision as to whether to enrol their animal on a clinical trial, often

recruitment can be frustrating either because the pet owners “don’t trust the drug companies” or they see

clinical trials as a last resort or they don’t want their pet to receive placebo.

Gruen, Jiamachello et al. (2014) conducted a survey of cat owners to determine the factors that greatest

influenced their decision as to whether to participate in clinical trials with their cats. Of the 366 completed

surveys, the greatest factors that influenced participation in decreasing order of importance were: trust in the

organisation (drug company), potential benefit for their cat, whether the veterinarian recommended the

clinical trial, the number of visits the cat would have to make to the vet, the benefit to other cats, the ability to

withdraw from the trial at any stage, the number of visits the owner would have to make, the advancement of

veterinary knowledge and finally recommendation by a friend was the least important factor influencing their

decision. Seventy one percent of owners who had previously participated in a clinical trial would consider doing

so again. Of respondents, 38% indicated that they would consider participating in a clinical trial with their cat,

44% were unsure about participation, and 18% indicated that they would not consider participating. It

appeared that free diagnostics and evaluation of their cat was a positive incentive to participating in clinical

trials. The authors also concluded that “though trial features are clearly important, trial design, advertisement

and explanation emphasizing the benefit to cats, and encouraging the endorsement of primary care

practitioners can enhance participation in clinical trials with cats”.

2.10 A Holistic Approach

Despite many dogs and cats geting diagnosed with cancer each year, shock is a typical reaction among caretakers.

Learning that their pet has cancer can be a very stressful, and often devastating experience. As with human

health, this has fuelled the need for emotional support and information. A holistic approach to pet cancer that

includes more than conventional veterinary medicine has been advocated by some in the animal health sector.

Figure 3: Holistic approach

Reproduced from: https://www.holisticpetcentre.com/canine-cancer/complimentary-alternative-medicine-

cam-intergrated-medicine/

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Chapter 3: The Animal Health Companies Cited in this Report

Overview

The animal health industry is experiencing a shift towards novel therapeutics for companion animals, driven by

the global increase in numbers of pets and the humanization of dogs and cats (Animal Pharm Top 50

Companies, 2018). Indeed, the animal health industry, which is usually several steps behind human medicine in

terms of innovation, is narrowing the gap and becoming more of an advanced space. In addition, the start up

scene in animal health has been burgeoning, especially in the USA, resulting in a diverse network of companies

providing a new source of product innovation. Many of these companies are recognizing that animal health

offers a shorter and cheaper route to the market than the human pharma market, and that sales of an animal

health product helps fund human R&D. Here we briefly profile the companies mentioned elsewhere in this

report, but it is likely this is not an exhaustive list of companies currently active in this space. Certainly, the pet

cancer market is dominated by the small and medium sized companies with limited financial resources, with

only 4 of the companies profiled below featuring in the top 50 ranked animal health companies based on sales

2013-2017 (Elanco, Boehringer, Virbac and Zoetis). Most of these companies are currently in the development

phase with their pet cancer products.

3.1 AB Science

AB Science was founded in 2001 by a team of researchers, clinicians and entrepreneurs, and

specialises in targeted therapies through tyrosine kinase inhibitors for treating diseases such as cancer, chronic

inflammatory diseases and neurological degenerative disorders in both human and veterinary medicine

(http://www.ab-science.com/en/). The Company’s turnover is entirely generated by the commercialization of

their only pet cancer drug. For the first half of 2018, this amounted to €872K, as compared with €842K one year

earlier, which represents an increase of 3.6% (http://www.ab-

science.com/file_bdd/content/1538376038_ABSCIENCEpressreleaseS12018-EngVF.pdf). They are developing

the same product for use in human cancer.

3.2 Anivive Lifesciences

Anivive Lifesciences, a privately-held biotech company focused on

innovations in the veterinary drug and bioinformatics space. The company was incorporated in 2015 and is

based in Long Beach, California. Members of the team include individuals who have held senior positions at

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Chapter 4: Regulation of Pet Cancer Products

There are very diverse veterinary product registration procedures across the world. However, the United States

and European markets tend to be the key drivers for the definition of global development programs, in

particular for complex diseases such as pet cancer. This chapter will focus on the authorities in these regions.

4.1 The United States (US) and European (EU) Regulatory Authorities

In the US, the regulation of animal health products is shared between several

agencies. The Food and Drug Administration’s (FDA) Centre for veterinary Medicine (CVM) is responsible for

animal drugs, animal feed (including pet foods) and veterinary devices. Veterinary biologics, including vaccines

and monoclonal antibodies are regulated by the U.S. Department of Agriculture (USDA). Both agencies have

recent experience of reviewing and approving pet cancer products. Guidance as to which agency has authority

for the regulation of a particular product type is available (Ruell et al., 2016).

The European Union currently maintains four different procedures and multiple regulatory

authorities for the registration of veterinary medicinal products. Historically, each EU Member State

maintained its own National Procedure which required national assessments and resulted in licences valid only

in one country. However, as, individual assessment of the same data set can result in different label claims, the

concept of harmonisation between Member States was introduced in the early 1990s via the Mutual

Recognition Procedure. Shortly afterwards, the European Medicines Agency (EMA) was created to enable the

European Commission to issue pan-European marketing authorisations valid in all Member States; this is the

Centralised Procedure. In 2005, a fourth procedure was added (Decentralised Procedure) which has many

similarities with the Mutual Recognition Procedure in that it aims to harmonise assessments and label claims

between the Member States included in the procedure. These procedures currently co-exist in Europe and

many products, particularly innovative ones such a pet cancer therapies, have a number of registration

procedure options open to them. Recently assessed pet cancer products in Europe have used the

Centralised Procedure.

4.2 Regulatory Guidance

The US and the EU, together with Japan are members of the International Cooperation on

Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH). The VICH

harmonises technical requirements for the conduct of studies necessary for the registration of a veterinary

medicinal product. Typically, a VICH guideline describes how a study should be conducted to satisfy quality,

safety or efficacy data requirements. VICH also covers data requirements for post-marketing

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Table 4: Summary of Veterinary Cancer Registries (Active and Dormant)

Country Established Species Status Comments

Switzerland 1955 Dogs and

cats

Active Swiss Canine Cancer Registry: Grunzig et al.,

2015; Swiss Feline Cancer Registry: Graf et al.,

2016

USA -

countrywide

1964 Dogs and

cats

Active Veterinary Medical Database (VMDB, 2010. The

Veterinary Medical Database)

http://www.vmdb.org

USA -

countrywide

2013 Dogs and

cats

Active Formerly the Texas Veterinary Cancer

http://texasvetcancerregistry.com/ Registered

now the National Veterinary Cancer Registry

http://nationalveterinarycancerregistry.org/

ITALY

Piedmont

area

2001 Dogs Unknown Baioni, 2017

ITALY Genoa

1985 Dogs and

cats

Unknown Registry of Animal Tumours/the Canine Cancer

Registry of Genoa

Merlo et al., 2008

ITALY Vicenza

and Venice

Dogs Active Animal Tumour Registry of the Vicenza and

Venice Provinces of the Veneto Region Vascellari

et al., 2009

DENMARK

2005 Dogs and

cats

Active Danish Veterinary Cancer Registry

Brønden et al., 2010

NORWAY

1990 Dogs Active Norwegian Canine Cancer Registry

Gamlem et al., 2008

USA Perdue

University

1978 Dogs cats Dormant Perdue Comparative Oncology Programme

Brønden et al., 2007

USA - Cornell

University

Dogs and

cats

Dormant Cancer Registry and Surveillance System for

Companion Animals, Cornell

Page et al., 2004

USA –

California

1968 Dogs and

Cats

Dormant California Animal Neoplasm Registry

Dorn et al., 1968

USA – Tulsa,

Oklahoma

1972 Dogs and

cats

Dormant Mac Vean et al., 1978

USA -

countrywide

1994 All species Dormant VetCancer Registry,

http://www.vetcancerregistry.com

UK 2007 Dogs and

cats

Dormant Managed by the Royal Veterinary College

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Chapter 6: Pet Cancer - Current Management Modalities for common tumours

6.1 Mast Cell Tumours

Mast cell tumours (MCT) are considered amongst the most common and most malignant skin cancer of dogs,

representing 16-21% of all skin tumours. MCTs represent about 20% of skin tumours diagnosed in cats. There is

a distinct breed predisposition Boxers, Labrador Retrievers, Golden Retrievers and Boston terriers are over

represented as breeds. The mean age at presentation is 7-9 years. Most MCTs occur on the trunk with the limb

and head/neck are the second and third most common locations, they are very heterogeneous in presentation.

They can present as single of multiple skin masses and readily metastasize to visceral or systemic mastocytosis.

Mean survival in dogs with advance mast cell tumours is typically in the region of four months. The image

below shows a mast cell tumour in a dog (left) and in a cat (right).

Figure 7: Mast Cell Tumours

Reproduced from: https://www.rvc.ac.uk/vetcompass/news/research-news-%E2%80%93-vetcompass-study-

on-mast-cell-tumours-in-dogs and http://www.petcancercenter.org/Cancer_Types_mast_cell_cat.html

A European consensus document has been developed to standardise the diagnosis and treatment of MCTs and

similar guidelines exist in the USA (Blackwood et al. 2012, Biller et al. 2016). Current treatment options for

MSTs in dogs are:

Surgery with or without radiotherapy: For low to intermediate grade accessible tumours, surgery with or

without follow up radiation and/or chemotherapy therapy is recommended, but this strategy only applies to

easily accessible tumours where wide resection margins can be obtained. The objective of this treatment is to

reduce the incidence of local recurrence and metastasis. For less accessible tumours low or intermediate grade

tumours, limb amputation with radiotherapy and chemotherapy is advocated. For highly aggressive tumours,

all treatment options are usually used including radical excision where possible.

Traditional Chemotherapy: Several protocols have been developed for the control of MCTs in dogs using drugs

that were initially developed for human use. These include, prednisolone, vincristine, cyclophosphamide,

vinblastine and lomustine, developed in protocols in various combinations. Partial and overall responses vary

from 0% to approximately 50% (Miller et al. 2016; Withrow and Vail, 2007).

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at a starting dose of 3.25mg/kg every other day. The dose is titrated according to the dog’s tolerance and is

administered for a duration dependent upon the dog’s response to treatment.

Figure 19: Palladia

Original development program: A number of studies with Palladia were carried out either in laboratory

dogs or in animal patients in veterinary practices or hospitals

(https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/860).

All clinical studies were conducted in the USA.

The pivotal clinical study was a GCP-compliant placebo-controlled double blinded, randomised field study. It

was carried out in two phases in 151 dogs with mast cell tumours. In a first phase (up to six weeks), Palladia

was compared with placebo. If there was disease progression, treatment with Palladia was stopped and the

dog was taken out of the study. After six weeks (second phase), the study continued with all the remaining

dogs receiving Palladia for an average of another four and a half months. The primary efficacy endpoint was

‘Objective Response rate ‘(OR: an evaluation by the veterinarian of the way the tumour changed during

treatment) and the ‘Time to Tumour Progression (TTP: time taken until the tumour started to get worse). The

OR for Palladia vs placebo was 37.2% vs 7.9% (p<0.001) and the TTP was 9 weeks vs 3 weeks. The main adverse

effects concerned the gastrointestinal tract (diarrhoea and vomiting).

Further development: Palladia remains the only pet cancer pharmaceutical fully approved in both the USA and

Europe. Since approval, Palladia has been further evaluated and shown a degree of efficacy in other solid

tumour types (eg anal gland anal sac adenocarcinoma), and in combination with other therapies (eg piroxicam)

(London, 2015). However, the current indications have not been amended.

7.3 Masivet (AB Science)

Overview: Masivet (masitinib mesylate) is a tyrosine kinase inhibitor that was originally conditionally approved

in the USA (under the name Kinavet-CA1) in 2010 for the treatment of recurrent (post-surgery) or

nonresectable Grade II or III cutaneous mast cell tumors in dogs that have not previously received radiotherapy

and/or chemotherapy except corticosteroids, with patent protection until 2023. In Europe, Masivet was

approved in 2008 for the ‘Treatment of non-resectable dog mast cell tumours (Grade 2 or 3) with confirmed

mutated c-KIT tyrosine kinase receptor’. It is available as 50mg or 150mg tablets, administered at a starting

dose of 12.5mg/kg every day. The dose is titrated according to the dog’s tolerance and is administered for a

duration dependent upon the dog’s response to treatment.

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Initially awarded a conditional license by the USDA in 2007, Oncept achieved full approval in the USA in 2010.

However, in Europe an application submitted in 2013 was withdrawn in 2014 as the company felt that

additional investment in the research and development required to answer the remaining regulatory issues

was not justified.

Figure 23: VET JET system

Reproduced from:

http://www.oakhamvethospital.co.uk/images/cache/08609551270f1acbb76033a0c23361f9_w320.jpg

Development program: The vaccine was developed through a partnership between Merial and Memorial Sloan-

Kettering Cancer Center. While Memorial Sloan-Kettering was testing a human melanoma vaccine, they

received an inquiry from Dr Philip Bergmann seeking novel treatments for canine melanoma. The discussions

resulted in clinical trials which refined the dosage and protocol to the current therapeutic regimen for dogs

(Grosenbaugh et al., 2011). The initial clinical work on ONCEPT was completed at Animal Medical Center in

New York. The USDA issued a conditional U.S. Veterinary Biological Product License for ONCEPT in 2007. During

the period of conditional licensure, ONCEPT was available to veterinary oncologists as Merial conducted

additional research to further support the safety and efficacy of the vaccine. The results of that research led to

the full licensure of ONCEPT. Merial obtained licensing rights from Memorial Sloan-Kettering and Dr. Philip

Bergman, and, using their access to and experience with DNA vaccine technology licensed from Vical

Incorporated, completed the industrialization and regulatory requirements for full licensure.

Further development: There is currently further clinical development ongoing in the USA to investigate Oncept

for the treatment of melanoma in horses. Due to this, Oncept can be offered as a treatment for European

horses under the cascade system at specialist equine centers. In addition, Oncept has been successfully

evaluated for safety in cats (Sarbu et al., 2015).

8.3 Oncept IL-2 (Merial/Boehringer Ingelheim)

Overview: Oncept IL-2 (also known as Feline Interleukin-2 Immunomodulator in the USA) is indicated for

immunotherapy to be used in addition to surgery and radiotherapy in cats with fibrosarcoma (2-5 cm diameter)

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