The Future of HIV Treatment

Greg PerryMelbourne – International AIDS Conference

July 2014

1

The Future of HIV Treatment?All people on treatment have access to the best possible regimens

Treatment side effects are minimal or non-existent

People can stay on the same treatment without developing resistance

Cost is no longer a barrier in determining which treatment to take

The most effective regimens are available as once-daily single tablet regimens or in long-acting formulations

Children have access to the best possible treatment that is suitable for their age

2

Recent progress in HIV treatment

• According to UNAIDS 12.9 million PLHIV were accessing treatment in end 2013

• Drugs with higher toxicity (e.g. d4T) are being replaced with better drugs

• Price of TDF-based first-line treatment has come down significantly in most countries

• Lower cost second line treatments increasingly available in many developing countries

3

New Medicines Being Developed

• 4 new ARVs approved since 2011

• 2 new single tablet regimens since 2011 and more in development

• There are new drugs with lower side effects and potential for being cheaper than current drugs

• Long-acting formulations under study that could enhance treatment options

4

Some Challenges

1. Accelerating availability of new ARVs in developing countries

2. Ensuring new ARVs become available in the most suitable

formulations

3. Promoting robust market competition to bring down prices of

new treatments

9.7 million have

access to treatment

5

PATENT HOLDERS

LicencesSub-Licences Medicines

MANUFACTURERS PEOPLE LIVING WITH HIV

ROYALTIES

Medicines Patent PoolPartnering for Innovation and Access

Established in 2010 with the support of

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1. Accelerating Availability of New ARVs in Developing Countries

77

Long Lag from Originator Market Approval to Generic Availability

FDA/EMA Approval

0 1 2 3 4 5 6 7 8 9 10

Timeline From Originator Approval to Generic Availability:

Generic Approvals

Years

• Time from FDA approval of new ARV molecules to availability of quality assured generics for developing countries has generally been between 5 to 10 years

Could the future look like this?

FDA/EMA Approval

0 1 2 3 4 5 6 7 8 9 10

Generic Approvals

Years8

1985 1990 1995 2000 2005 2010 2015 2020 2025 2030

TRIPS Transition for

Developing Countries TRIPS Transition for Least Developed Countries Zidovudine Didanosine Stavudine Saquinavir Nevirapine Abacavir Emtricitabine Lamivudine Indinavir Efavirenz

Darunavir1985 1990 1995 2000 2005 2010 2015 2020 2025 2030

` Lopinavir Atazanavir Tenofovir Disproxil Fumarate (TDF) Fosamprenavir Maraviroc Etravirine

Tenfovir Alfenamide Fumarate (TAF) Rilpivirine Raltegravir Elvitegravir

Ritonavir heat-stable Dolutegravir Cobicistat 1985 1990 1995 2000 2005 2010 2015 2020 2025 2030

* Secondary patents on some of these products may extend patent protection beyond the date shown.

Patents on new ARVs could delay the timeline even further

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Accelerating availability of new medicines in developing countries through voluntary licensing

Drug Approval in US (FDA)

Approval in Europe (EMA)

Expiry of main patent

Date of MPP licence

Projected filing for market approval by MPP Sub-licensees(estimate - subject to change)

Cobicistat August 2012*

September 2013

2027 July 2011 mid-2015

Elvitegravir August 2012*

November 2013

2023 July 2011 mid-2015

Dolutegravir August 2013

January 2014

2026 April 2014 2016

Tenofovir Alafenamide Fumarate (TAF)

Not yet approved (in phase III clinical trials)2015 ?

2021 Very soon 2017/2018?

Availability of quality generics can be accelerated by licensing medicines during final phase of development or shortly after approval and managing licences to accelerate development and registration

10* As part of the QUAD

2. Ensuring ARVs Become Available In The Most Suitable Formulations

1111

Licensing to Facilitate Fixed Dose Combinations

• Fixed-dose combinations improve treatment adherence for adults and children alike

• But face particular patent challenges:

• Patents on one component can impact access to entire regimen

• Patents on the combinations

No patent

Patented

Patented

No patent

Patented, but licensed to MPP

• Within the MPP, patents are “pooled” in one place, easing the development of new FDCs

Patented, but licensed to MPP

ARV Formulations For Children

• Simpler treatment options• Suitable for different age groups• Fixed-dose combinations

Current pediatric formulations of HIV medicines are often inappropriate (e.g. alcohol based, bitter liquids, require refrigeration, not available as FDCs).

Key missing formulations identified by WHO Paed AIDS Working Group

• AZT or ABC/3TC/LPV/r • ABC/3TC/EFV• DRV/r• TDF/3TC(or FTC)/EFV)• ATV/r• RAL• DTG based combinations• COBI as an alternative booster to RTV 13

The Paediatric HIV Treatment Initiative

Goal: To ensure that appropriate and affordable medicines are available to the World’s 3.3 million children living with HIV.

Key focus: partner with all stakeholders to:• Share IP and data on formulations

and access • Accelerate development of urgently

needed paediatric ARV formulations• Effectively shape the paediatric HIV

market

Launched in May 2014. A UNITAID-MPP-DNDi-CHAI initiative

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New ARV formulations for adults

Most recently approved single tablet regimens:• TDF/FTC/EVG/COBI• TDF/FTC/RPV

Fixed-dose combinations under development:• ABC/3TC/DTG• TAF/FTC/EVG/COBI• TAF/FTC/DRV/COBI

Other combinations recommended by the CADO 2 Conference for study that could be equally or more potent, durable and affordable than currently recommended treatments:• TAF/3TC(or FTC)/EFV• TAF/3TC(or FTC)/DTG• DTG+DRV/r

Green: Licensed to the MPP

or in negotiationsBlack: Compound patent expired or licensed bilaterallyOrange: Not currently

licensed

Note: licences cover countries accounting for 87% to 93.4% of PLHIV in developing countries, depending on the licence

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3. Promoting Robust Market Competition For New Patented ARVs

1616

Role of market competition in price reduction: case of tenofovir

2006 2007 2008 2009 2010 2011 2012 2013$0.00

$50.00

$100.00

$150.00

$200.00

$250.00

TDF 300mg price

2 34

6 7FDA or WHO-PQ approved generic ver-sion of TDF 300mg

5

8 9

Lowest price for TDF 300mg and number of quality-as-sured generics on the market (not available in all

countries)

1

Medicines Patent Pool Out-Licensing

• MPP

Sublicensees

Aurobindo

Cipla

Desano

Emcure

Hetero

Laurus

Micro Labs

Mylan

Shasun

Shilpa

Promoting robust generic competition through non-exclusive licensing to qualified manufacturers

MPP has licensed 7 ARVs to 10 generic partners:• Tenofovir Disproxil

Fumarate• Emtricitabine• Elvitegravir• Cobicistat• Abacavir paediatric• Atazanavir• Dolutegravir

Currently managing 35 sub-licences

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Key Challenge: inclusion of certain middle-income countries in licences

2000 2010 20200%

20%

40%

60%

80%

100%

70%

37%

13%

High

Upper middle

Lower middle

Low

Income category

Proportion of people living with HIV by country income category, 2000 - 2020

Source: UNAIDS, IMF 2012

One possible approach to address challenge in some MICs

• Market Segmentation (public/private)

– In many countries, national treatment programs cater for vast majority of people on treatment

– Generics able to supply national treatment programs

– Originators continue to cater for small private market

• Introducing royalties that are differentiated according to countries’ socio-economic circumstances

– Enables countries to benefit from robust generic competition which results in lower prices

– Royalty could take into account different variables: GDP per capita, inequality, disease burden, others