|Applicable indicator||Not applicable|
Novartis is among the top performing large research-based pharmaceutical companies, following close behind the leaders. This is driven by strong performance in Manufacturing & Production and Appropriate Access & Stewardship. Its performance in Research & Development is on par with the average for this group of companies. The company has an antimicrobial R&D pipeline of 32** projects, of which 16 target a priority pathogen, including two novel antimalarial candidates. It has an access commitment in place for four of its R&D candidates. The company discloses a comprehensive environmental risk-management strategy, which includes discharge limits and reportedly applies to all Novartis’ third-party suppliers of antibiotic APIs and drug products. Novartis has filed its newest antibiotics in some countries in scope* and commits to engaging in inter-country equitable pricing for its antimicrobials. The company reports that it widely applies intra-country equitable pricing for one product. It also reports engaging with local healthcare facilities to align supply and demand. Regarding stewardship, Novartis engages in numerous AMR educational activities aimed at healthcare professionals, taking steps to mitigate conflict of interest, and is currently adjusting incentives for its sales teams to increase the weight of fixed pay in overall compensation and to reduce the variable component. In contrast to other large research-based pharmaceutical companies in scope, Novartis does not report engaging in antibiotic-specific AMR surveillance programmes.
Sales & operations
Novartis is a large research-based pharmaceutical company with three divisions: Innovative Medicines, Alcon (eye-care products) and Sandoz (generic medicines). The Innovative Medicines division has two business units: pharmaceuticals (primary care and specialty medicines) and oncology. The bulk of antimicrobial medicines in the company’s portfolio are marketed by Sandoz. Sandoz markets antimicrobials in about 140 countries globally, of which 71 or more are low- or middle-income countries.* Sandoz also sells other drug products, pharmaceutical intermediates and active pharmaceutical ingredients (APIs). It sold and/or donated 2,425 million doses of antimicrobial medicines during the fiscal year 2016. In 2015, Novartis divested its vaccine business (excluding influenza vaccines) to GSK in an asset swap that included the acquisition of GSK’s marketed oncology portfolio. The influenza vaccines unit ceased operation in 2014 and was finally acquired by CSL Limited in 2015 (including its development pipeline).
Novartis markets at least 67 antimicrobial medicines, the second largest reported antimicrobial portfolio among the large research-based pharmaceutical companies assessed by the Benchmark. Sixty of these 67 medicines are listed on the WHO EML (Section 6). The bulk of the company’s antimicrobial medicines are classical fermentation-derived antibiotics (penicillins, cephalosporins and macrolides), marketed by its generics division Sandoz. Of 41 antibiotics on the market, 36 are listed on the WHO EML (Section 6), including three antibiotics in the EML’s Reserve group (cefepime, daptomycin and linezolid). The remainder (26) of the company’s portfolio includes antivirals, antifungals, antiprotozoals and anthelminthics, the majority of which are listed on the WHO EML (Section 6).
Plan ahead for access and stewardship during R&D. Novartis has a general registration procedure in place for candidates that reach Phase III clinical development, and has specifically stated a commitment to apply this to its late-stage candidates. Novartis can ensure that this procedure is applied, while also implementing further access and stewardship plans for all its candidates in late-stage clinical development.
Improve transparency regarding environmental risk management. Novartis can share more information on how it manages environmental risk, e.g., the company can disclose the levels of antibiotic discharge. Currently, Novartis discloses several elements of its environmental risk-management strategy.
Expand environmental risk-management strategy. Novartis can apply its antibiotic discharge limits to third parties who manufacture antibiotic APIs on its behalf. Novartis has set discharge limits for its own manufacturing sites and external waste-treatment plants as part of its environmental risk-management strategy.
Engage in more stewardship activities. Novartis engages in several stewardship activities. The company can engage in antibiotic resistance surveillance programmes, collaborate with public health authorities and ensure that data is made publicly available through open databases.
Expand its SMS for Life programme to more countries. Novartis can expand its SMS for Life (2.0) programme, a public-private partnership between Novartis and local public health facilities to track medicines stock levels, to more countries in scope.* The programme is already operating in six African countries.
A. Research & Development
32 projects, 16 target priority pathogens
A.1 Average antimicrobial R&D investments.
Novartis reports investments in antimicrobial R&D in 2016, which are average compared to other large research-based pharmaceutical companies in the Benchmark, however the exact amount is confidential. These investments cover antimicrobial medicines only, as Novartis is not involved in vaccine development.
A.2.1-2.2 Pipeline focused on gram-negative bacteria and malaria.
Novartis has 32** antimicrobial R&D projects in its pipeline, seven of which are in clinical stage development. Sixteen of the company’s projects target priority pathogens. It has an average-sized pipeline compared to other large research-based pharmaceutical companies assessed by the Benchmark. The company has a strong focus on malaria and bacteria, mostly gram-negative. It has nine drug candidates in preclinical development (eight of which target bacteria), and four drug candidates in clinical development. Novartis’ clinical pipeline consists of four investigational medicines including: two novel antimalarial medicines (both imidazolopiperazines); LFF571 (an antibiotic targeting C. difficile in Phase II development); and LYS228 (an antibiotic with activity against carbapenem-resistant Enterobacteriaceae spp. (CRE), currently starting Phase II clinical trials). Additionally, Novartis is awaiting approval for the inclusion of tuberculosis as an additional indication for its leprosy medicine, clofazimine (Lamprene®).
A.3 Six R&D projects being developed with public partners, including two PDPs.
Novartis is developing six R&D projects in its priority pathogen pipeline through public-private partnership (including non-profit organisations). Two antimalarial candidates, cipargamin and KAF156/lumefantrine, are being developed through PDPs with the Medicines for Malaria Venture (MMV). Development of KAF156/lumefantrine is co-funded by the Bill & Melinda Gates Foundation and development of cipargamin is co-funded by the Wellcome Trust. The other four projects are in preclinical stage and involve public research institutes.
A.4 Access commitment in place, but no information regarding stewardship.
Novartis reports that it has an access commitment in place for its four R&D candidates targeting priority pathogens in late-stage development, but reports no information on stewardship provisions. In the 2016 Access to Medicine Index, Novartis was a leader in registering products in countries in scope.* The company commits to applying the same strategy to its latestage investigational candidates. For example, the PDP funding agreements for its antimalarial candidates include clauses to ensure broad access. Regarding stewardship provisions, Novartis signed the Davos Declaration, which includes a general commitment to support the appropriate and responsible use of antimicrobial medicines and vaccines. After the period of analysis, Novartis stated its practice of initiating global surveillance for potential resistance to its novel antimicrobial agents a minimum of four years prior to expected launch (in line with FDA recommendations).
Pipeline targeting priority pathogens
B. Manufacturing & Production
B.1 Comprehensive environmental risk-management strategy.
Novartis undertakes almost all environmental risk-management activities that the Benchmark examines. Namely, it applies an environmental risk-management strategy to minimise the impact of antibiotic manufacturing discharge. This includes auditing at its own manufacturing sites and those of third-party manufacturers of antibiotic APIs and drug products. Novartis sets limits on antibiotic discharge for its own manufacturing sites and external waste-treatment plants, yet not to third-party manufacturers of antibiotic APIs and drug products.
B.2 Limited transparency regarding environmental risk management.
Novartis publishes elements of its environmental risk-management strategy on its website. It does not disclose audit results, or the discharge levels of antibiotics. The company also does not share the identities of its third-party suppliers of antibiotic APIs and drug products or external waste-treatment plants.
B.3 Commits to following GMP, including at 3rd-party sites.
Novartis reports that it has mechanisms for maintaining a high quality of antibiotic production — namely following GMP standards. This commitment applies to its own manufacturing sites. Novartis requires its third-party suppliers of drug products to apply the same quality standards to their production facilities.
C. Appropriate Access & Stewardship
C.1 Filed newest antibiotics in some countries in scope.
Novartis reports information about where it has filed five of its newest antibiotics for registration in some countries in scope* (between one and eight countries). These products were introduced between 2011 and 2017.
C.2 Inter- and intra-country equitable pricing.
Novartis discloses a general (not product-specific) commitment to applying inter-country equitable pricing to its highest-volume antimicrobials including antibiotics. It applies intra-country equitable pricing approaches for artemether/lumefantrine (Coartem®) in the majority of countries in scope.* This approach was first developed and implemented in partnership with WHO in 2001. Novartis has independently extended this approach beyond its initial ten-year term.
C.3 Local engagement to align supply and demand.
Novartis engages with primary and local healthcare facilities to align supply and demand forecasting for two of its highest-volume antimicrobial medicines: artemether/lumefantrine (Coartem®) and efavirenz. This applies in the following countries in scope*: Cameroon, the Democratic Republic of Congo, Ghana, Kenya, Nigeria and Tanzania. Alignment of supply and demand for these products is managed through SMS For Life, a public-private partnership between Novartis and local healthcare facilities set up to track stock levels. Initially established for mobile phones, the programme was updated in Nigeria in 2016 to include a tablet- and smartphone- based version of its stock-level tracking platform.
C.4 Multiple activities in AMR-related educational programmes.
Novartis reports that it is involved in educational programmes for HCPs that include AMR stewardship and rational use of antibiotics, with conflicts of interest (COI) mitigation measures in place. Programmes include topics on diagnosis, treatment and management of multidrug-resistant bacterial infections. The company provides a protocol to mitigate COI. All educational activities reported were developed in collaboration with third parties.
C.5 Comprehensive involvement in appropriate promotion practices.
The Benchmark measures how companies address stewardship through appropriate promotion. Novartis reports that it takes action in this regard: it reflects AMR trends in its marketing materials and is currently adjusting incentives for its sales teams around the world. For example, the company has started to increase the weight of fixed pay in overall compensation and to reduce the variable component.
C.6 Implements brochure and/or packaging adaptations to facilitate appropriate use.
Novartis has adapted several brochures (to include demographic and literacy considerations) to facilitate appropriate use of antibiotics by patients. For example, paediatric brochures have been incorporated to illustrate the appropriate dosage of amoxicillin, and the packaging for its penicillin G antibiotic in Africa has been adapted for patients who may be illiterate.
C.7 No apparent involvement in surveillance programmes.
Novartis reports no involvement in antibiotic resistance-specific programmes aimed at increasing global surveillance capabilities.
* Countries in scope are 106 low- and middle-income countries where access to medicine is likely limited.
** After the period of analysis, Novartis submitted an adaptive project of tobramycin for the treatment of bronchiectasis-related Pseudomonas, including the assessment of resistance.
† EML Section 6: Anti-Infective Medicines
§ Net sales; FYE 31 December 2016