N - ViiV | Paediatric HIV

2020 HIV TREATMENT

29. Support and facilitate long-term follow up in the ODYSSEY trial, including long-term safety profile data.

30. Support the Impaact P2019 study to evaluate ABC/3TC/DTG for children under 12 years including new dispersible tablet formulation.

31. With CHAI and Unitaid, expedite development of a dispersible fixed dose combination of pediatric ABC/3TC/DTG with Aurobindo and Viatris.

32. Supporting rapid product introduction and broad access post-registration for both originator and generic versions of dispersible paediatric DTG.

40. Through novel collaborative approaches, enable marketing authorisation applications in target NRA countries (Botswana, Malawi, Namibia and Zimbabwe) in parallel to the EMA assessment to accelerate national registration of DTG 5mg dispersible tablets

41. Utilise the WHO CRP process in other African countries to enable quickest possible registration of DTG 5mg dispersible tablets.

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.

Updates

June 2022

Clinical data updates

We would like to highlight the following publications:

Ruel TD, Acosta EP, Liu JP, et al. Pharmacokinetics, safety, tolerability, and antiviral activity of dolutegravir dispersible tablets in infants and children with HIV-1 (IMPAACT P1093): results of an open-label, phase 1-2 trial. Lancet HIV. 2022 May;9(5):e332-e340.
Waalewijn H, Chan MK, Bollen PDJ, et al. Dolutegravir dosing for children with HIV weighing less than 20 kg: pharmacokinetic and safety substudies nested in the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. Lancet HIV. 2022 May;9(5):e341- e352.
Singh RP, Adkison KK, Baker M, et al. Development of Dolutegravir Single-entity and Fixed- dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237.

Regulatory updates

On 30th March ViiV received U.S. Food and Drug Administration (FDA) approval for Triumeq PD (abacavir/dolutegravir/lamivudine, 60mg/5mg/30mg), a dispersible tablet formulation of the fixed dose combination of abacavir, dolutegravir and lamivudine for the treatment of pediatric patients weighing 10kgs to <25 kgs with human immunodeficiency virus type 1 (HIV- 1). In addition, a supplemental new drug application (sNDA) was approved for Triumeq tablet (abacavir/dolutegravir/lamivudine, 600mg/50mg/300mg), lowering the minimum weight that a child with human immunodeficiency virus type 1 (HIV-1) can be prescribed this medicine from 40kgs to 25kgs.
In December 2021, ViiV also made a similar regulatory submission for Triumeq to the European Medicines Agency (EMA) – review is ongoing.
ViiV is on track for the submission of our second sNDA for Triumeq PD to the US FDA to extend the licence to children weighing more than 6kg by the end of 2022.
With regards to our ongoing regulatory activities for Tivicay (dolutegravir), for the revised dosing for the 50mg tablet and the new 5mg dispersible tablet dose form, we have continued to make good progress submitting to several National Regulatory Authorities utilising the WHO Collaborative Registration Procedure, national procedures and other accelerated approval processes.
Regulatory Authority submission and approvals update are updated quarterly and accessible from our website: Improved Access To Our HIV Medications | ViiV Healthcare.
ViiV-CHAI/Unitaid and Gx initiative to expedite generic DT formulations
We are encouraged by the breadth of adoption of generic DTG 10mg DT through 2021 as a result of the technology transfer programme between ViiV, CHAI/Unitaid and Mylan (now part of the Viatris Group) and Macleods and the subsequent catalytic procurement programme funded by Unitaid, in addition to the standard procurement pathways with USAID, The Global Fund and countries.
The partnership programme between ViiV, CHAI and Unitaid and Mylan (now part of the Viatris Group) and Aurobindo to expedite generic development of a dispersible tablet formulation of the fixed dose combination of DTG/ABC/3TC is progressing well. Mylan (Viatris) and Aurobindo will provide updates on their respective development programmes and estimated timelines.

March 2022

International Meetings participation:

Triumeq (abacavir, dolutegravirand lamivudine): IMPAACT2019 study data presented as poster at CROI 2022 conference, 12- 16 Feb2022, Virtual meeting: Brooks KM, et al. IMPAACT2019: PK & SAFETY OF DISPERSIBLE ABC/DTG/3TC IN CHILDREN WITH HIV 6TO <14 KG. Poster737
Tivicay ( dolutegravir): ODYSSEY study publication in New England Journal of Medicine, 30 Dec 2021: Turkova A, et al. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. N Engl J Med 2021; 385:2531-2543. DOI:10.1056/NEJMoa2108793

Regulatory updates

ViiV has received confirmation of priority review status from the U.S. FDA for our regulatory submissions at the end of September 2021 tointroduce a new dispersible tablet formulation ofTriumeq ( abacavir, dolutegravir and lamivudine) and to extend its current approval tolower the minimum weight at which a child can be prescribed Triumeq, from 40kg and above to 14kg and above. Target approval date isexpected by the end of Ql 2022.
In December 2021, ViiV also made a similar regulatory submission forTriumeq to the European MedicinesAgency(EMA).
With regards to our ongoing regulatory activities for Tivicay (dolutegravir), for the revised dosing for the 50mg tablet and the new 5mgdispersible tablet dose form, we have continued to make good progress submitting to several National Regulatory Authorities utilisingthe WHO Collaborative Registration Procedure, national procedures and other accelerated approval processes.
Regulatory Authority submission and approvals update are updated quarterly and accessible from our website:lmprovedAccessToOurHIV Medications I ViiV Healthcare.

ViiV-CHAI/Unitaid and Gx initiative to expedite generic DTformulations

We are encouraged by the breadth of adoption of generic DTG 10mg DT through 2021 as a result of the technology transfer programme between ViiV, CHAI/Unitaid and Mylan ( now part of the Viatris Group) and Macleods and the subsequent catalytic procurement programme funded by Unitaid, in addition to the standard procurement pathways with USAID, The Global Fund and countries.
The tech transfer programme and partnership between ViiV, CHAI and Unitaid and Mylan (now part of the Viatris Group) and Aurobindo to expedite generic development of a dispersible tablet formulation of the fixed dose combination of DTG/ABC/3TC is progressing well.

October 2021

Clinical data updates: We would like to highlight the following presentations at international meetings:

DTG ODYSSEY study: A total of 6 presentations at IAS & HIV Paediatric Workshop 2021, IAS 2021 (1 oral, 5 posters) – including the <14 kg cohort week 96 data as Late Breaker, which showed superiority vs standard of care.
HIV Paediatric Workshop (2 oral, 3 posters)
ABC/DTG/3TC IMPAACT 2019 study: Preliminary results presented at IAS & HIV Paediatric Workshop 2021 on the pharmacokinetics and safety of dispersible and immediate Release
FDC Abacavir/Dolutegravir/Lamivudine in Children with HIV Weighing ≥14 kg

Regulatory updates

Today we announced that ViiV has made regulatory submissions to the U.S. Food and Drug Administration (FDA) to introduce a new dispersible tablet formulation of Triumeq (abacavir, dolutegravir and lamivudine) and to extend its current approval to lower the minimum weight at which a child can be prescribed Triumeq, from 40kg and above to 14kg and above.
With regards to our ongoing regulatory activities for Tivicay (dolutegravir), for the revised dosing for the 50mg tablet and the new 5mg dispersible tablet dose form, we have continued to make good progress submitting to several National Regulatory Authorities utilising the WHO Collaborative Registration Procedure, national procedures and other accelerated approval processes.
Regulatory Authority submission and approvals update are updated quarterly and accessible from our website: Improved Access To Our HIV Medications | ViiV Healthcare.
ViiV-CHAI/Unitaid and Gx initiative to expedite generic DT formulations
We are very excited that as a result of the technology transfer programme between ViiV, CHAI/Unitaid and Mylan (now part of the Viatris Group) and Macleods and the catalytic procurement programme funded by Unitaid and through standard procurement pathways with USAID, The Global Fund and countries, that dispersible DTG is now reaching a number of African countries and starting to benefit CLHIV.
The tech transfer programme and partnership between ViiV, CHAI and Unitaid and Mylan (now part of the Viatris Group) and Aurobindo to expedite generic development of a dispersible tablet formulation of the fixed dose combination of DTG/ABC/3TC is progressing.

April 2021

Clinical data updates

In relation to our commitment to support and facilitate long-term follow up in the ODYSSEY trial – 96 week data was presented recently at CROI 2021, the positive clinical data presented was well received by conference attendees and provides further support for the efficacy and safety of the use of DTG in paediatric populations.

Regulatory updates

In January 2021, we received marketing authorisation from the EMA for the dolutegravir 5mg DT tablet formulation for Europe following the CHMP Positive Opinion in Nov 2020 as well as an expanded indication for the previously approved oral solid dose 50mg tablet formulation.
Further to receipt of the EMA approval, we have been preparing our submission to the WHO Collaborative Registration Procedure to register the dispersible DTG 5mg formulation and enable access in a number of African countries. We are aiming to submit by the end of April 2021, aligned with WHO CRP guidance.
Last year, we worked with the WHO collaborative registration team and the European Medicines Agency (EMA) and country National agencies in Botswana, Malawi, Namibia and Zimbabwe to create an innovative “hybrid registration” approach to enable review of our dolutegravir 5mg DT tablet applications in parallel with the EMA review. We are delighted to confirm that we have now received approval from Botswana and Namibia and wait to hear from the other 2 countries involved in this novel approach in the next few months.
More broadly, we continue to make good progress on regulatory submission plans in other countries around the world.
ViiV-CHAI/Unitaid and Gx initiative to expedite generic DT formulations
We are delighted with the progress and achievements from our partnership with CHAI and Unitaid and Mylan (now part of the Viatris group) and Macleods to expedite generic development of a scored 10mg dispersible tablet formulation of DTG with both companies now having received tentative FDA approval within 9 months of ViiV’s approval.
We are excited that very soon, as a result of Unitaid and CHAI’s catalytic procurement project, children will start to benefit from this innovative partnership programme and medicine.
The tech transfer programme and partnership between ViiV, CHAI and Unitaid and Mylan and Aurobindo to expedite generic development of a dispersible tablet formulation of the fixed dose combination of DTG/ABC/3TC is progressing.

2018 TREATMENT

Updates

Action 43:

On 12 December 2019, ViiV filed regulatory submissions to both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for a 5mg dispersible-tablet formulation of dolutegravir (DTG), as well as a simplified dosing regimen to optimise use of the existing DTG 50mg film-coated tablet in paediatric HIV patients. EMA has validated the submission and FDA accepted the application for priority review with expected decision in June 2020.

ViiV/CHAI/Unitaid partnerships with Mylan and Macleods to expedite generic development of a scored 10mg dispersible tablet formulation of DTG - all activities are on track including confidential, official correspondence with the FDA regarding the filing strategy.
Engagements with donors, Governments and implementers have commenced to enable product introduction planning for the new dispersible formulation(s) – ViiV’s and the Gx - but more to be done here – we count on collaboration with partners to make implementation successful.
Unprecedented collaborative efforts between PENTA/ODYSSEY, WHO, VIIV and IMPAACT: deep and intimate involvement and collaboration to facilitate the submission by December 2019.
April 2020:
- We are responding to information requests and remain focussed on our PDUFA goal date of the 12th June with the FDA. We expect to receive the first round of questions from the EMA in the next few weeks.
- Whilst we also continue to make good progress on regulatory submission plans internationally, we unfortunately now anticipate some delays due to COVID-19 impacting the operations of some regulatory authorities. We are working to understand the impact of COVID-19 on these submissions and remain committed to working with regulators to minimise any delays.
- The cross-functional paediatric team at ViiV has been expanded to support post approval product introduction of the new dispersible formulation of dolutegravir as well as progress plans to ensure continued data generation to support practical clinical use in key paediatric groups, such as those co-infected with TB.
- ViiV/CHAI/Unitaid partnerships with Mylan and Macleods to expedite generic development of a scored 10mg dispersible tablet formulation of DTG are progressing well.
- Engagements with donors, Governments and implementers are ongoing to enable product introduction planning for the new dispersible formulation(s) – ViiV’s and the Gx. We count on active collaboration with partners to make sure implementation is successful post FDA approval – this will become even more critical given the complexities the COVID-19 pandemic is introducing for HIV programmes.
June 2020: The U.S. Food and Drug Administration (FDA) has now approved Tivicay PD (dolutegravir) tablets for oral suspension, which are used in combination with other antiretroviral agents for the treatment of HIV-1 in paediatric patients (treatment-naïve or -experienced but INSTI- naïve) aged at least four weeks and weighing at least 3kg. In addition, they have approved an extended indication to expand the use of the already approved Tivicay 50mg film-coated tablet to include paediatric HIV patients weighing 20kg and above.

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

14. Explore use of CRP mechanism for DTG dispersible tablets: had productive meeting with the CRP team in January where made it clear that ViiV intends to use CRP mechanism, while hoping to tweak it so they can initiate the process more quickly because need to use it with EMA as a reference rather than FDA. Next stage is to discuss with EMA if that will be possible prior to full EU approval. Would happen in 2020.

20. In order to minimise the time between anticipated FDA approval and delivery to programmes, based on indicated volume demand to-date by procurers, ViiV has agreed to start manufacturing the 5mg DT formulation at ViiV’s risk (i.e. without purchase orders).

43. Continue to work closely with FDA & EMA, IMPAACT and PENTA to strive to meet target submission date of December 2019 for DTG 5mg dispersible tablet and expanded weight band indication for 50mg.

2017 ROME ACTION PLAN

Action 6: Prioritize PADO products in research and development plans.

Action 13: In pre-clinical and clinical development, initiate paediatric formulation development as soon as a given drug shows potential public health impact in adults, soon after Phase II trials are completed.

Action 14: Include adolescents when conducting initial adult efficacy trials, where possible and practical, or conduct parallel trials with the goal of providing information to support licencing for adolescents at the same time as adults.

Action 15: In the design of paediatric PK and safety studies, use weight-based dosing and enroll all children above 4 weeks concurrently, unless a strong rationale exists for not doing so.

Action 17: Engage in early and regular consultations with the PAWG on PIP/PSPs, as well as recommended dosing and ratios for FDC development.

Action 18: Take all possible measures to rapidly complete development of priority paediatric drugs and formulations in the pipeline, with the goal of providing the maximum number of new formulations by end of 2018, especially for infants and young children.

Action 30: Strengthen and expand collaboration to overcome intellectual property challenges and otherwise facilitate technology transfer and knowledge sharing that can promote faster paediatric formulation development, including on challenges like taste-masking.

6. (individual commitment) ViiV Healthcare committed to deploy people, resources and technical expertise to speed up as much as possible the generation of data for regulatory approval of medicines for children living with HIV, including the ongoing development of Dolutegravir for children.

7. (individual commitment) ViiV Healthcare committed to make paediatric Dolutegravir available at cost of production in low income countries, least developed countries and across Sub-Saharan African countries until generics are available.

Updates

Action 6:

ViiV has committed additional resources to Pediatrics and has convened a cross‐functional team to address possible ways to accelerate development of DTG for pediatrics. Delivery against our commitments in paediatric HIV is a key objective for ViiV globally.

Action 13:

ViiV has appointed a Paediatric Medicines Development Lead (MDL) who will further increase resource and focus in paediatrics. The MDL will work across the whole of ViiV’s R&D portfolio to bolster the portfolio approach to ViiV’s efforts in paediatric ARV development.

Action 18:

On 12 December 2019, ViiV filed regulatory submissions to both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for a 5mg dispersible-tablet formulation of dolutegravir (DTG), as well as a simplified dosing regimen to optimise use of the existing DTG 50mg film-coated tablet in paediatric HIV patients. EMA has validated the submission and FDA accepted the application for priority review with expected decision in June 2020.

Action 30:

On 18 July 2018, ViiV and CHAI/Unitaid made a joint announcement to paediatric HIV stakeholders to announce the launch of a partnership to speed up development and introduction of optimized pediatric formulations of dolutegravir for children living with HIV in resource‐limited settings. The initiative provides Mylan and Macleods (who both have voluntary licences for paediatric DTG through the Medicines Patent Pool) with a financial incentive award from Unitaid via CHAI, as well as the technical expertise of ViiV Healthcare, to catalyze thedevelopment, manufacture and supply of generic formulations of pediatric dolutegravir. https://www.viivhealthcare.com/media/press‐releases/2018/july/innovative‐publicprivate‐partnership‐initiative‐to‐accelerate‐development‐of‐optimal‐pediatricformulations‐of‐dolutegravir‐to‐improve‐the‐lives‐of‐clhiv.aspx.

ViiV confirmed (in a meeting with PEPFAR) their intention to provide paediatric drugs at access pricing until generics are available, and potentially beyond in LMIC.