Osteoarthritis in Dogs: Novel Therapeutic Advances What's New? - Aratana Therapeutics
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Osteoarthritis in Dogs: Novel Therapeutic Advances
What’s New?
Lesley Rausch-Derra, DVM, MS
Vice President of Regulatory Affairs and Drug Development, Aratana Therapeutics
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 1
©2016 Aratana
Provided April 2,Therapeutics,
2016, as part ofInc. Confidential.
an oral Alland
presentation Rights Reserved.
the speaker and/or Aratana disclaims any duty to update.
Safe Harbor Statement Special Note Regarding Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements with respect to our ability to bring several innovative products to market; expectations regarding the timing or scope of commercialization of Galliprant; and the Company’s plans and opportunities, including without limitation offering innovative therapeutics that fulfill serious unmet needs. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our history of operating losses and expectations of losses for the foreseeable future; failure to obtain sufficient capital to fund our operations; risks relating to the impairment of intangible assets AT-004, AT- 005, AT-007 and AT-011; effects of unstable market and economic conditions; restrictions placed on our operating and financial flexibility by the terms of our credit facility; our substantial dependence on the success of certain of our product candidates; our dependence on novel technologies and compliance with complex regulatory requirements; our inability to obtain regulatory approval for our existing or future product candidates; the lack of commercial success of our current or future product candidates; our inability to realize all of the anticipated benefits of our acquisitions and difficulty integrating acquired businesses; the uncertainty of outcomes of the development of pet therapeutics, which is a lengthy and expensive process; effects of competition; our inability to identify, license, develop and commercialize additional product candidates; our failure to attract and keep senior management and key scientific personnel; our reliance on third-party manufacturers, suppliers, and partners; regulatory restrictions on the marketing of our product candidates; unanticipated difficulties or challenges in the relatively new field of biologics development and manufacturing; our small commercial organization; difficulties managing the growth of our organization; our significant costs of operating as a public company; risks related to the restatement of our financial statements for the year ended December 31, 2013 and the identification of a material weakness in our internal control over financial reporting; changes in distribution channels for pet therapeutics; consolidation of our customers; limitations on our ability to use our net operating carryforwards; impact of generic products; unanticipated safety or efficacy concerns; our limited patents and patent rights; our failure to comply with our intellectual property license obligations; our infringement of third party patents and challenges to our patents or rights; litigation resulting from the misuse of our confidential information; the uncertainty of the regulatory approval process; our failure to comply with regulatory requirements or obtain foreign regulatory approvals; our failure to report adverse medical events related to our products; legislative or regulatory changes; the volatility of our stock price; our status as an "emerging growth company," as defined in the JOBS Act; the potential for dilution if we sell shares of our common stock in future financings; the influence of significant stockholders over our business; and effects of anti-takeover provisions in our charter documents and under Delaware law. These and other important factors discussed under the caption "Risk Factors" in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC, on March 15, 2016, along with our other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this presentation. ©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 2 Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.
A Prostaglandin E2 (PGE2) EP4 Receptor Antagonist
or
EP4 PRA
For the control of pain and inflammation associated with
osteoarthritis (OA) in dogs
FDA approved March 2016
IMPORTANT SAFETY INFORMATION: GALLIPRANT® (grapiprant tablets) is for use in dogs only. Do not use in dogs younger than 9
months of age and less than 8 lbs (3.6 kg), dogs used for breeding, or in pregnant or lactating dogs. Adverse reactions in dogs may
include mild gastrointestinal effects including, vomiting, diarrhea and decreased appetite. Should not be used in dogs that have a
hypersensitivity to grapiprant. Avoid use with COX-inhibiting NSAIDs or corticosteroids. Please see the full Prescribing Information.
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 3
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 4 Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.
Safety Study
Evaluation of the safety of
long term (9 month), daily oral
administration of grapiprant, a
novel drug for treatment of
osteoarthritic pain and inflammation,
in healthy dogs
Pharmacokinetic comparison of oral tablet and suspension formulations
of grapiprant, a novel therapeutic for the pain and inflammation of
osteoarthritis in dogs
– Rausch-Derra et al., Journal of Veterinary Pharmacology and Therapeutics.
Online 29Mar16
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 5
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Safety Study
Tested at up to 15X the labeled dose of 2 mg/kg
for 9 months
Study Dose Grapiprant Flavored Tablet Exposure of Flavored Tablet
(mg/kg/day) of methylcellulose Equivalent (mg/kg/day) Based Equivalent based on AUC ratios with
suspension Upon Mean AUC Ratios 3 mg/kg as the 1X safety dose*
0 0 Control
1.0 0.75 0.25X*
1.48X*
6.0 4.5
(2.24X the labeled dose)
10.16X*
50.0 30.5
(15.25X the labeled dose)
*Safety dose defined as the highest dose to which a dog of any weight could be exposed
when using whole or half tablets
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 6
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Safety Study
9-month Safety Study Results
– No effect on: food consumption, body weight, ECG, organ weight,
hematology, coagulation
– Dose dependent and mild GI signs: soft stools, sporadic emesis, stools
with mucus or blood. Seen in all groups including controls
– No treatment effect on BUN/creatinine, liver enzymes or platelets
– Mild decrease in total protein, albumin, Ca++ (reversible; dose and time
dependent)
– Histopathology: No effect on liver, kidney, stomach
1 dog in the tablet equivalent of 30.5 mg/kg had mild mucosal regeneration
of ileum
No gastric ulcers seen in any dog.
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 7
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Efficacy Study
A prospective, randomized, masked, placebo-controlled multi-site
clinical study of grapiprant, an EP4 prostaglandin receptor antagonist
(PRA), in dogs with osteoarthritis.
Rausch-Derra L., Huebner M., Wofford J., Rhodes, L.
Journal of Veterinary Internal Medicine In Press
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 8
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Efficacy Study
Pivotal Study Objective:
– to evaluate the safety and effectiveness of
GALLIPRANT tablets dosed at 2 mg/kg once daily for
28 days when compared to a placebo, for the pain and
inflammation associated with osteoarthritis in dogs
Study Design:
– prospective, randomized, masked, placebo-controlled,
multi-site study conducted under Good Clinical
Practice (GCP) Guidelines
– 16 Veterinary Hospitals participated in the study
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 9
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Efficacy Study
Treatment Groups:
– GALLIPRANT dosed at 2 mg/kg with
20, 60 or 100 mg tablets
– Placebo (vehicle without active) dosed in tablet size and
shape to match active
– Randomized in a 1:1 ratio in blocks of four
– No restrictions on prandial state when dosed
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 10
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Efficacy Study
Efficacy Assessment:
– Owner assessed Canine Brief Pain Inventory (CBPI)
Validated assessment tool (Brown, Boston and Coyne, AJVR 2007;
Brown, Boston and Coyne, JAVMA 2008)
Completed on Days 0 (baseline), 7, 14, 21 and 28.
– Veterinarian assessment (total orthopedic score)
Completed at screening and Days 7 and 14
Safety Assessment:
– Physical exam at each visit
– CBC, chemistry and urinalysis
Completed at screening and Day 28 or if removed early
– Adverse events
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 11
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Canine Brief Pain Inventory
Pain Severity Score (PSS)
– Score is the mean of these questions (range 0-10)
– Minimum score of 2 to be eligible for study
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 12
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Canine Brief Pain Inventory
Pain Interference Score (PIS)
– Score is the mean of these questions (range 0-10)
– Minimum score of 2 to be eligible for study
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 13
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Canine Brief Pain Inventory
From where did choice of entry criteria and
success criteria come?
Brown, Bell and Rhodes, AJVR 2013
Proven successful in pilot study
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 14
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Canine Brief Pain Inventory
Overall Impression
– Choice of five categories
– No minimum evaluation to be eligible for study
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 15
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Efficacy Study
Success Criteria - CBPI Results
Treatment Success*
% (N)
GALLIPRANT® Placebo
Study Day p-value
(N=131) (N=131)
7 30.5% (40) 16.0% (21) 0.0154
14 41.2% (37) 28.2% (37) 0.0442
21 46.6% (61) 32.8% (43) 0.0443
28 48.1% (63) 31.3% (41) 0.0315
*10 control dogs and 1 Galliprant dog were removed from the study early due
to lack of effectiveness and considered treatment failures.
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 16
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Efficacy Study
CBPI Pain Severity Scores (PSS) over time
Mean percentage change (with 95% confidence intervals ) in PSS from Day 0 to Days 7, 14, 21 and 28
* denotes statistical significance (pEfficacy Study
CBPI Pain Interference Scores (PIS) over time
Mean percentage change (with 95% confidence intervals ) in PIS from Day 0 to Days 7, 14, 21 and 28
* denotes statistical significance (pEfficacy Study
Adverse Events
– Most commonly reported were vomiting, diarrhea/soft
stool, anorexia/inappetence
– Self-limiting, most resolved after a few days Grapiprant Placebo
(N=141) (N=144)
Vomiting Number of Dogs with Evaluations 24 9
Mean Number of Days Affected per Affected Dog 1.75 1.50
Minimum Number of Days 1 1
Maximum Number of Days 5 3
Diarrhea/Soft Stool Number of Dogs with Evaluations 17 13
Mean Number of Days Affected per Affected Dog 1.94 1.69
Minimum Number of Days 1 1
Maximum Number of Days 5 4
Anorexia/Inappetence Number of Dogs with Evaluations 9 7
Mean Number of Days Affected per Affected Dog 2.67 2.86
Minimum Number of Days 1 1
Maximum Number of Days 4 7
– No dog was removed from the study due to an adverse
event related to treatment
– No clinical pathology changes noted
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 19
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.Conclusions
Targeted mechanism of action
focuses on major receptor-ligand pathway responsible
for pain and inflammation in osteoarthritis
9-month safety data to 15X labeled dose of
2 mg/kg
No adverse effects on liver, kidney, or GI
ulceration
Pivotal field study confirmed safety and efficacy
First drug to be approved using validated
assessment tool, CBPI
©2016 Aratana Therapeutics, Inc. Confidential. All Rights Reserved. 20
Provided April 2, 2016, as part of an oral presentation and the speaker and/or Aratana disclaims any duty to update.You can also read
