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PDR001Product Analysis

Ref Code: DMKC0192025Author: Michael Ramirez

Product Analysis : PDR001 2

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Published on 23 May 2018



CONTENTS

LIST OF FIGURES

LIST OF TABLES

4 OVERVIEW

4 Drug Overview

5 Product Profiles

5 PDR001 : Melanoma

8 Figure 1: PDR001 for melanoma – SWOT analysis

9 Figure 2: Datamonitor Healthcare’s drug assessment summary of PDR001 for melanoma

10 Figure 3: Datamonitor Healthcare’s drug assessment summary of PDR001 for melanoma

12 Figure 4: PDR001 sales for melanoma across the US, Japan, and five major EU markets, by country, 2017–26

6 Table 1: PDR001 drug profile

7 Table 2: PDR001 ongoing late-phase trial in melanoma

13 Table 3: PDR001 sales for melanoma across the US, Japan, and five major EU markets, by country ($m), 2017–26

15 Table 4: PDR001 patient numbers for melanoma across the US, Japan, and five major EU markets, by country, 2017–26




OVERVIEW

DRUG OVERVIEW PDR001 (Novartis) is a fully humanized monoclonal antibody designed to inhibit the negative immunoregulatory receptorprogrammed death-1 (PD-1). PDR001 blocks the interaction between PD-1 and its ligands, programmed death-ligand 1 (PD-L1) andPD-L2; the signaling elicited by this interaction inhibits T-cell activation. Therefore, disrupting the interaction allows T-cells to becomeactivated, and mount cytotoxic effects against cancer cells. PDR001 is being tested in several combinations in addition to as a monotherapy across various cancer types, including incombination with mitogen-activated protein kinase (MAPK) inhibitors Tafinlar (dabrafenib; Novartis) and Mekinist (trametinib;Novartis/Japan Tobacco) in previously untreated unresectable or metastatic BRAF V600-mutant melanoma. Although PDR001 facessteep competition from established marketed PD-1 inhibitors Opdivo (nivolumab; Bristol-Myers Squibb/Ono Pharmaceutical) andKeytruda (pembrolizumab; Merck & Co), it may benefit from the fact that these drugs are not in development in combination withMAPK inhibitors. However, pipeline drug Tecentriq (atezolizumab; Roche/Chugai), a PD-L1 inhibitor, is in a Phase III trial in a triplecombination with MAPK inhibitors Zelboraf (vemurafenib; Roche/Chugai/Daiichi Sankyo) and Cotellic (cobimetinib; Exelixis/Roche) forBRAF V600-mutant unresectable locally advanced or metastatic melanoma. If approved, this combination could compete strongly withPDR001.




Product Profiles PDR001 : Melanoma PRODUCT PROFILE

ANALYST OUTLOOK PDR001 is a cornerstone of Novartis’s immuno-oncology program, and is being tested in several combinations in addition to as amonotherapy across various cancer types, including in combination with mitogen-activated protein kinase (MAPK) inhibitors Tafinlar(dabrafenib; Novartis) and Mekinist (trametinib; Novartis/Japan Tobacco) in previously untreated unresectable or metastatic BRAFV600-mutant melanoma. Although PDR001 faces steep competition from established marketed programmed death-1 (PD-1)inhibitors Opdivo (nivolumab; Bristol-Myers Squibb/Ono Pharmaceutical) and Keytruda (pembrolizumab; Merck & Co), it may benefitfrom the fact that these drugs are not in development in combination with MAPK inhibitors. However, pipeline drug Tecentriq(atezolizumab; Roche/Chugai), a programmed death-ligand 1 (PD-L1) inhibitor, is in a Phase III trial in a triple combination with MAPKinhibitors Zelboraf (vemurafenib; Roche/Chugai/Daiichi Sankyo) and Cotellic (cobimetinib; Exelixis/Roche) for BRAF V600-mutantunresectable locally advanced or metastatic melanoma. If approved, this combination could compete strongly with PDR001.

DRUG OVERVIEW PDR001 is a fully humanized monoclonal antibody designed to inhibit the negative immunoregulatory receptor PD-1. PDR001 blocksthe interaction between PD-1 and its ligands, PD-L1 and programmed death-ligand 2 (PD-L2); the signaling elicited by this interactioninhibits T-cell activation. Therefore, disrupting the interaction allows T-cells to become activated, and mount cytotoxic effects againstcancer cells (Alsaab et al., 2017).




DEVELOPMENT OVERVIEW Novartis took on PDR001 in its acquisition of immuno-oncology startup CoStim in 2014 (Novartis press release, 2015). PDR001 iscurrently being tested in a Phase III trial (ClinicalTrials.gov identifier: NCT02967692) evaluating its use in combination with Tafinlar andMekinist in previously untreated unresectable or metastatic BRAF V600-mutant melanoma patients. This trial was initiated in January2017, and its estimated primary completion date is July 2019. Novartis has announced that it plans to file a New Drug Application(NDA) based on this trial in 2019 (Novartis investor presentation, 2017).

ONGOING LATE-PHASE TRIALS The ongoing clinical trial is summarized in the table below.

Table 1: PDR001 drug profile

Molecule PDR001

Phase of development Phase III

Mechanism of action PD-1 inhibitor

Originator Novartis

Marketing company Novartis

Formulation Intravenous

Alternative names PDR-001

PD-1 = programmed death-1

Source: Biomedtracker



Table 2: PDR001 ongoing late-phase trial in melanoma

Trial Sample size Target patients Study design Dosing Primary endpoints Study start/primarycompletion date

NCT02967692(Phase III)

538 Previously untreated, BRAFV600 mutation-positivepatients with unresectable ormetastatic melanoma

Randomized, parallel-assignment, quadruple-blind (participant, careprovider, investigator,outcomes assessor),treatment trial

Arm 1: PDR001 + Tafinlar +MekinistArm 2: Tafinlar + Mekinist

PFS determined byinvestigator usingRECIST guidelinesIncidence of dose-limiting toxicitiesImmunemicroenvironment andbiomarker modulation

January 2017/July 2019

PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors

Source: ClinicalTrials.gov




SWOT ANALYSIS

CLINICAL AND COMMERCIAL ATTRACTIVENESS

Figure 1: PDR001 for melanoma – SWOT analysis

Source: Datamonitor Healthcare; Biomedtracker




The figures below depict Datamonitor Healthcare’s assessment of PDR001’s clinical and commercial attractiveness as a therapy formelanoma in relation to all of the other key marketed and pipeline drugs profiled. Figure 2: Datamonitor Healthcare’s drug assessment summary of PDR001 for melanoma

Source: Datamonitor Healthcare




For more information about how PDR001 compares to other marketed drugs and pipeline agents for melanoma, please refer to theMarket Dynamics chapter of the melanoma forecast. PATIENT BASED FORECAST

FORECAST ASSUMPTIONS Datamonitor Healthcare makes the following assumptions in its forecast of PDR001 for melanoma:

REGULATORY

COMPETITION

Figure 3: Datamonitor Healthcare’s drug assessment summary of PDR001 for melanoma


PDR001, in combination with Tafinlar and Mekinist, is expected to gain approval for first-line treatment of BRAF V600-positivemelanoma in Q2 2020 in the US and in Q3 2020 in Japan and the five major EU markets (France, Germany, Italy, Spain, and theUK). Approval in this setting will be based on PDR001’s pivotal Phase III study (ClinicalTrials.gov identifier: NCT02967692).

•

PDR001 is expected to compete with marketed immune checkpoint inhibitors Opdivo, Keytruda, and Yervoy (ipilimumab;Bristol-Myers Squibb/Ono Pharmaceutical), as well as MAPK-targeted inhibitors Zelboraf and Cotellic; these regimens are allused in the BRAF V600-positive patient population.

•


https://service.datamonitorhealthcare.com/disease/oncology/skin-cancer/malignant-melanoma/forecast/article191403.ece



DOSING

PRICING

PDR001 FORECAST, 2017–26

Novartis’s combination of PDR001/Tafinlar/Mekinist will compete with Roche’s combination of Tecentriq/Zelboraf/Cotellic in thefirst-line treatment of BRAF V600-positive unresectable or metastatic melanoma upon initial approval of Roche’s combination inQ3 2020.

•

No melanoma-specific dosing information is currently available for PDR001. However, based on a Phase I clinical trial protocol inadvanced solid tumors, Datamonitor Healthcare assumes that patients treated with PDR001 will receive 400mg every fourweeks (ClinicalTrials.gov identifier: NCT02404441) (Naing et al., 2016).

•

As pricing was not available at the time of the forecast, Datamonitor Healthcare assumes PDR001 will be priced similarly tofellow PD-1/PD-L1-targeted therapy Keytruda. Datamonitor Healthcare uses national formularies to gather pricing informationper product and applies backing-out formulas to adjust formulary prices in order to obtain estimates of ex-factory wholesaleprices in each country.

•

Please view the accompanying datapack for a full table of drug costs per patient per year.•




Figure 4: PDR001 sales for melanoma across the US, Japan, and five major EU markets, by country, 2017–26




Table 3: PDR001 sales for melanoma across the US, Japan, and five major EU markets, by country ($m), 2017–26

Country 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026

US - - - 11.2 41.9 94.8 137.9 155.1 162.7 170.5

Japan - - - 0.1 0.5 1.1 1.5 1.7 1.7 1.7

France - - - 1.6 9.1 21.2 31.5 35.0 35.4 35.7

Germany - - - 1.5 8.1 18.6 27.2 30.2 30.5 30.7

Italy - - - 1.1 5.8 13.0 18.8 20.7 20.8 20.9

Spain - - - 0.9 5.1 12.1 18.0 20.0 20.3 20.4

UK - - - 0.8 4.6 10.7 15.9 17.9 18.3 18.6

Grand total - - - 17.2 75.0 171.4 250.8 280.5 289.6 298.5

Note: totals may not sum due to rounding.




Table 4: PDR001 patient numbers for melanoma across the US, Japan, and five major EU markets, by country, 2017–26

Country 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026

US - - - 242 812 1,446 1,761 1,813 1,845 1,877

Japan - - - 4 14 24 30 31 31 31

France - - - 76 304 572 718 741 748 755

Germany - - - 76 297 549 687 709 714 720

Italy - - - 42 158 287 354 363 364 366

Spain - - - 32 130 247 311 321 324 327

UK - - - 38 153 289 366 381 389 395

Grand total - - - 509 1,869 3,415 4,227 4,359 4,416 4,470

Note: totals may not sum due to rounding.





BIBLIOGRAPHY Alsaab H, Sau S, Alzhrani R, Tatiparti K, Bhise K, et al. (2017) PD-1 and PD-L1 Checkpoint Signaling Inhibition for CancerImmunotherapy: Mechanism, Combinations, and Clinical Outcome. Frontiers in Pharmacology, 8, 561. Naing A, Gelderblom H, Gainor J, Forde P, Butler M, et al. (2016) A first-in-human phase I study of the anti-PD-1 antibody PDR001 inpatients with advanced solid tumors. Journal of Clinical Oncology, 34, no 15_supplemental, 3060. Novartis investor presentation (2017) Q1 2017 Results. Available from: https://www.novartis.com/sites/www.novartis.com/files/q1-2017-ir-presentation.pdf [Accessed 25 October 2017]. Novartis press release (2015) Novartis highlights strong innovation momentum at its second Meet Novartis Management investor day.Available from: https://www.novartis.com/news/media-releases/novartis-highlights-strong-innovation-momentum-its-second-meet-novartis [Accessed 26 October 2017].


https://www.novartis.com/sites/www.novartis.com/files/q1-2017-ir-presentation.pdf

https://www.novartis.com/sites/www.novartis.com/files/q1-2017-ir-presentation.pdf

https://www.novartis.com/news/media-releases/novartis-highlights-strong-innovation-momentum-its-second-meet-novartis

https://www.novartis.com/news/media-releases/novartis-highlights-strong-innovation-momentum-its-second-meet-novartis

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PDR001700 clients across the pharma and biotech industries, we are relied upon to provide strategic guidance, not only through published analysis, but also tailored support solutions