2020 HIV TREATMENT

26. Ensure innovation to improve the health of children by supporting CHAI and PENTA in their commitment to accelerate development, registration and catalytic launch of DRV/r 120/20 mg optimal pediatric fixed dose combination and provide DRV API from 2021-23.

27. Support approaches that track access to pediatric patients and to continued transparency around its HIV & TB pediatric work.

28. Enhance collaboration and facilitate knowledge-sharing to promote development of new technologies to enhance effectiveness and acceptability of paediatric medicines, including long-acting injectables for infants and adolescents (Rilpivirine).

43. Through PENTA and IAS CIPHER, work together to develop an enhanced monitoring and safety data platform for new and existing paediatric ARV drugs.

44. Convene or participate in a series of virtual consultations of key stakeholders in 2020-2021 to develop a model and mobilize resources for the platform.

45. In collaboration with EGPAF and other key partners, broaden the impact of the New Horizons Advancing Pediatric HIV Care Collaborative (NHC). The NHC currently provides support to its participating countries with health systems strengthening and access to Darunavir (DRV) & Etravirine (ETR) through donations (from Johnson & Johnson subsidiary Janssen Products LP). Starting in 2021, these two pillars of the program will be enhanced through further expansion of technical assistance in identifying and managing HIV treatment failure in children and adolescents, capacity building, evidence generation, supply chain management, and support for harmonized TB co-infection screening. Johnson & Johnson and the NHC team commit to seek additional stakeholders to support the expansion of these critical initiatives.

46. Continue to work with PEPFAR on catalytic procurement of DRV 75mg for children in the developing world.

47. Rapidly scale up the manufacture of new PADO priority pediatric ARV products (4-in-1 and DTG 10mg dispersible tablets) at a scale that will fully meet market demand as forecast by GAP-f partners and procurement agencies within 6 months of approval.

Updates

Commitment 28:

April 2021

  • In collaboration with ViiV Healthcare and Janssen, the IMPAACT Network initiated the MOCHA study in March 2019 to confirm the dosage and evaluate safety, tolerability, acceptability, and pharmacokinetics (PK) of oral CAB, CAB LA, and RPV LA in virologically suppressed HIV‐1 infected children and adolescents aged 12 to <18 years. The LATA study is also planned to evaluate the safety, efficacy and acceptability of the CAB LA + RPV LA versus standard of care in virologically suppressed HIV-1 infected adolescents 12 to 19 years of age in sub-Saharan Africa, beginning in 2022.

 

Commitment 45:

April 2021

  • Johnson & Johnson recognizes the significant gaps that remain in pediatric HIV & TB care, and as such is taking actions in an effort to broaden availability of pediatric treatments.   ​

  • In collaboration with EGPAF and the other key partners, Johnson & Johnson has committed to support the broadening of the multi-stakeholder consortium of New Horizons Advancing Pediatric HIV Care Collaborative (NHC). To support the planned mid-year launch of NHC’s expansion, two high-level meetings (Q1’21) have been conducted with key stakeholders to gain insights and alignment.  Also, quantitative and qualitative research has been conducted, demonstrating NHC’s impact to patients, caregivers, HCPs and MOH officials. These findings highlight NHCs evidence of value and are being built into the transition plan for NHC. The expansion of NHC offers new opportunities to optimize sequencing of antiretroviral regimens for children, adolescents and youth, strengthen healthcare systems and increase capacity to deliver high quality HIV prevention and care services. 

 

Commitment 46:

April 2021

  • Johnson & Johnson has been coordinating with CHAI and PENTA to support development, registration and catalytic launch (by a generic manufacturer) of Gx DRV/r 120mg/20mg optimal pediatric fixed dose combination through provision of DRV PK model data and continued coordination to plan logistics of the DRV API provision. 

2018 HIV TREATMENT

41. Ensure availability of DRV paediatric formulations in LMIC countries until DRVr FDC is available, and partner with GAP-f partners to develop transition plans to generic products once the generic FDC is available (expected in Q4 2020).

Updates

Commitment 41:

 

October 2020

Johnson & Johnson through Janssen Pharmaceutical NV, part of its Janssen Pharmaceutical Companies, is working with the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) on a catalytic procurement project for children in the developing world.  The parties have agreed on the quantity of Darunavir 75 mg required to support the initiative for 2019/2020, as such manufacturing and shipments have commenced, and product needs continue to be collected from countries. This year, Q1 and Q2 2020 orders have shipped, and orders for Q3 and Q4 2020 have been postponed until Q3/Q4 2021 due to insufficient demand from the countries. Johnson & Johnson production has planned accordingly.

To support Darunavir forecasting and production planning, the parties have agreed to share their respective pediatric demand/order forecast summaries with CHAI & the ARV Procurement Working Group (APWG). This has provided greater visibility to the collective pediatric Darunavir forecasted demand.

June 2020

Since the last update, Q1 and Q2 2020 orders have shipped, and orders for Q3 and Q4 2020 will be postponed until Q3 and Q4 2021 due to insufficient demand from the countries. Johnson & Johnson production has planned accordingly, and PEPFAR HQ is working with countries to identify eligible patients.

To support Darunavir forecasting and production planning, the parties have agreed to share their respective pediatric demand/order forecast summaries with CHAI & the ARV Procurement Working Group (APWG). This has provided greater visibility to the collective pediatric Darunavir forecasted demand.

Pharmaceutical companies, SRAs, WHO Prequalification Programme (PQ) and NRAs commit to:

1. Accelerate the national drug registration process to enable registration of any ARV listed by WHO EOI in around 40 participating countries within 1 year by ensuring that:


FOR PRODUCTS WITH PQ APPROVAL:

  • Company submits for registration in countries requesting use of the CRP (based on PQ approval) and process completed within around 4-5 months (country decisions within 3 months, plus submission processing time)

 

FOR PRODUCTS THAT HAVE NOT YET RECEIVED PQ APPROVAL:

  • Company submits with USFDA for full approval or tentative approval and process completed within 6 months;

  • USFDA approval or tentative approval review shared with WHO for Collaborative Registration

  • Procedure-lite (CRP-lite), a pilot program at first allowing FDA to share up to 5 minimally redacted reviews.

  • Company submits for registration in countries requesting use of the CRP (based on WHO PQ, FDA (CRP-lite) or other SRA review) and process completed in around 4-5 months (country decisions within 3 months, plus submission processing time)

13. Share their methodological approaches to acceptability studies (including palatability and ease of administration) and contribute to a repository held by GAP-f partners to guide future investigation of acceptability for paediatric products.

14. Consider the use of the CRP for national registration of pediatric ARV products on PADO, Optimal formulary and Limited use lists.

15. Ensure all drug registration dossiers meet minimum requirements at the time of filing and that responses to specific queries are complete and provided in a timely manner

20. Manufacture new PADO priority pediatric ARV products “at risk” such that the new product is available for supply at time of approval/tentative approval/prequalification, including validation of manufacturing process during regulatory review.

Updates
2020 TB TREATMENT

32. Ensuring ongoing access to the 20mg bedaquiline tablet, which Johnson & Johnson, in partnership with Stop TB Partnership's GDF Pediatric DR-TB Initiative, has already made available for over 130 countries, following US FDA approval in May 2020.

33. Continue efforts in exploring additional clinical trial sites to ensure timely completion of study investigating the use of bedaquiline in children below 5 years of age.

 

34. Engage early and regularly with GAP-f and other WHO-convened expert groups on pediatric indication development.

 

35. Engage with the Medicines Patent Pool and/or generic companies to evaluate licensing agreements for pediatric formulations, where appropriate.

 

36. Make pediatric formulations and data available to research networks advancing pediatric PK and safety studies, where appropriate under collaborative agreements. Rapidly submit data to regulatory authorities and the WHO to facilitate updating of labelling and recommendations.

 

37. Use the following best practices for the design and implementation of research studies:

  • Engage with regulators to explore options for pediatric studies as soon as a given drug shows promising efficacy and safety in Phase IIa adult studies.

  • Consider Including adolescents when conducting initial adult efficacy trials or conduct parallel trials with the goal of providing information to support licensing for adolescents at or near the same time as adults, when appropriate from a scientific and ethical perspective and allowed by regulations.

  • In the design of paediatric PK and safety studies, when appropriate from a scientific and ethical perspective and allowed by regulations, consider studying weight-based dosing and enrolling all children above 4 weeks of age concurrently (i.e., no age de-escalation).

  • Assess acceptability and palatability of formulations, including for use in low-resource settings, at the earliest appropriate stage of the formulation’s development.

 

38. Support the development of drug susceptibility testing (DST) and methods in parallel to new molecule development and make pure drug substance available for DST at the same time as the introduction of a new molecule.

87. Consider the use of the CRP for national registration of paediatric TB products.

88. Ensure all drug registration dossiers meet requirements at the time of filing and that responses to specific queries are complete and provided in a timely manner.

89. Consider facilitating existing joint assessment procedures by planning the submission in different countries/regions to allow for joint assessment in existing networks.

90. Provide multilingual Patient Information Leaflets or Instructions for Use to facilitate appropriate use by Healthcare workers and caregivers

91. Consider prioritizing registration submission of new TB pediatric products in high burden countries where import waivers cannot be granted.

Updates

Commitment 32:

April 2021

  • Since first approval in May 2020, 17 countries have accessed the 20mg bedaquiline tablet, the vast majority of which are through Stop TB Partnership's Global Drug Facility.    

Commitment 33:

April 2021

  • 1 new clinical trial site has been added since November 2020 bringing the total to 5, with 3 additional new sites expected in 2021.

Commitment 36:

April 2021

  • The SIRTURO® indication was expanded to MDR-TB patients 12 years above and weighing at least 30 kg in the US (2019) and in the EU (2020). 

  • Subsequently, in parallel with the registration of a pediatric formulation (20 mg tablet), the indication was further expanded to MDR-TB patients 5 years and above and weighing at least 15 kg in the US in May 2020 and in the EU in March 2021.

  • Janssen is sharing data on pediatric patients as soon as it’s available to inform WHO recommendations. The WHO Operational Handbook on DR-TB treatment, updated in 2020, includes the bedaquiline 20mg formulation.

Commitment 38:

April 2021

  • Johnson & Johnson is collaborating with stakeholders including the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and drug susceptibility testing device manufacturers to validate bedaquiline breakpoints that would inform the interpretation of DST results when tested using the MGIT 960 or Thermo Fisher dry 96-well microtiter plates. 

  • Johnson & Johnson, in partnership with the U.S. National Institutes of Health (NIH), has made pure bedaquiline substance available free of charge to nationally accredited laboratories globally for use in DST. Bedaquiline can be requested through the NIH AIDS Reagent Program (https://www.hivreagentprogram.org/). 

Commitment 87:

April 2021

  • The Collaborative Registration Procedure is being used in multiple Sub Saharan African countries including Rwanda, Uganda, Nigeria, Cameroon, Tanzania, Burundi, Namibia, Zambia, Ethiopia, Ghana, Kenya, Zimbabwe for the initial registration of bedaquiline to expedite national registrations. The use of the CRP will continue to expedite national registrations of the pediatric formulation and the pediatric indications.

Commitment 89:

April 2021

  • For the initial registration of bedaquiline, several regional joint assessment procedures have been used in Africa (EAC, ZAZIBONA, ECOWAS). They are being considered for the pediatric filings as well.

Commitment 90:

April 2021

  • Johnson & Johnson has worked with Stop TB Partnership's Global Drug Facility on a specific pack with the patient information leaflet in four languages (English, French, Spanish, Russian) most common in DR-TB high burden countries. The addition, on the outer box, of a web URL allows patients and healthcare practitioners to access a global list of Product Safety contacts, to use for Adverse Event and Product Quality Complaint reporting.  

Commitment 91:

April 2021

  • The bedaquiline 20 mg formulation has been approved in the US in May 2020 and in the EU in March 2021. Filings have now been submitted in India and Thailand, with additional country dossiers being prepared.