1. HIV Pipeline P P P P P Phase I Phase II Phase III TMB-60711
(MK-8122, PPL-100)
Protease inhibitor
Ambrilia TaiMed
GSK
Maturation Inhibitor
GSK
ABX464
Rev inhibitor5
Abivax
Dapivirine
(TMC120; DPV)
IVR for PrEP
NNRTI
Janssen  IPM
Filed with EMA
Doravirine2
(MK-1439; DOR)
NNRTI
Merck
Filed with USFDA
MK-4250
MOA unknown
Merck
GSK
Requires a booster
Maturation Inhibitor
GSK
VRC family8
(VRC01LS, VRC07, VRC07-523LS, 10E8VLS, N6LS …)
bNAbs against gp120
For prevention or treatment
NIH
Fostemsavir
(BMS )
Prodrug of BMS
Attachment inhibitor
BMS  ViiV
MK-8504
NRTI (TFV prodrug)
Merck
PRO-140 (PA14)3
Not for X4-tropic HIV
Entry inhibitor; mAb
(not an ARV)
CytoDyn
MK-8591 (EFdA)
NRTTI6
Merck
MK-8527
MOA unknown
Merck
Cabotegravir-LA
(GSK-744; CAB)
For PrEP
INI
ViiV
GS-9131
NRTI
Gilead
UB-4214
(TMB-355)
mAb against CD4
(not an ARV)
United Biopharma
(LS) + 3BNC117(LS)14
bNAbs against gp120
For prevention or treatment
Rockefeller; NIH
MK-8583
NRTI
Merck
Cenicriviroc7
(TBR-652; CVC)
Not for X4-tropic HIV
Entry inhibitor
Takeda  Tobira P
Vesatolimod (GS-9620)9
TLR7 agonist / Immunomodulator
(not an ARV)
Gilead
Cabotegravir-LA + Rilpivirine-LA
Maintenance strategy
ViiV + Janssen
PGDM PGT121
bNAbs against gp120
For prevention or treatment
IAVI
Sources: ClinicalTrials.gov; WHO ICTRP (international clinical trials registry platform); aidsinfo.nih.gov
Recent approvals:
- NNRTI named Elsulfavirine (VM1500), brandname Elpida® received approval in Russia on June 30, This product is not approved in the US or EU.
- Entry inhibitor named Albuvirtide (FB006M), brandname Aikening® received approval in China on June 5, Albuvirtide consists of large synthetic peptides given by IV. Note this is a different molecule from T-20 (enfuvirtide), it is not simply a long-acting version of T-20. This product is not approved in the US or EU.
Footnotes:
“Long-acting” defined as once monthly or less frequent. Owen A and Rannard S (2016) Advanced Drug Delivery Reviews 103, p144–156
Doravirine nanoformulations were also explored in a PK/bioavailability study. DOR and DOR/TDF/3TC were filed with USFDA in Jan 2018, action date expected in Oct 2018
PRO-140: Q1W SC injection, “self injectable”, humanized mAb against CCR5. In Ph2b/3, including as single agent maintenance strategy
UB-421 is a mAb against/targeting CD4 given as (likely biweekly) IV infusion. It is being investigated in Ph3 as a monotherapy in suppressing viral rebound in place of ART, and separately in Ph2 in combination with OBR for MDR-HIV
ABX464: potentially first-in-class, this oral candidate that targets the HIV Rev protein and prevents unspliced HIV RNA from being exported out of the nucleus, thereby blocking HIV replication
NRTTI stands for nucleoside reverse transcriptase translocation inhibitor. Ph2 on EfdA+DOR+3TC is scheduled to start in Nov 2017
Cenicriviroc: oral dual inhibitor of CCR2 and CCR5, does not work for X4-tropic virus. Development focus appears to have shifted from HIV treatment to non-alcoholic steatohepatitis (NASH). There is a Ph2 investigator-led trial on CVC for neuroAIDS
VRC01, a broadly neutralizing mAb targeting the CD4 binding site on gp120 (note not “targeting CD4”), is being studied in two large Ph2 studies (HPTN081 & 085) for the prevention of HIV infections. VRC01LS utilizes the Xtend antibody half-life extension technology from Xencor. The NIAID has progressed additional mAbs from the VRC family (VRC07, VRC07-523LS, 10E8VLS, N6LS) into Phase 1 studies
GS-9620: TLR activation has been linked with the stimulation of antiviral immunity. GS-9620 is a TLR7 agonist that could activate HIV production in late cells and may be potentially coupled with immunotherapy (therapeutic vaccine or bNAbs). GS-9620 development for hepatitis B has been discontinued.
Development of vicriviroc for HIV treatment was discontinued in Intravaginal rings containing vicriviroc are now being studied in Phase 1, with or without MK-2048 (combination IVR=MK-2048A)
TMB-607 (formerly known as PPL-100 from Ambrilia, and MK-8122 under Merck partnership that was terminated) is a PI discovered over a decade ago. It is now being investigated in Ph1 as nanoformulated IM or SC injection (likely monthly)
GS-6207 is a potential first-in-class capsid inhibitor. Described as having potential for “long-acting administration”, but not yet found in clinical trial registries and unclear what route of administration will be pursued.
GS-9722 is a bNAb and a derivative of PGT121. Not yet found in clinical trial registries. PGT121 family of antibodies that target gp120 and have also been shown to interfere with gp120’s binding to CD4 (allosterically)
PGT121 was licensed from Theraclone, which has proprietary I-STAR technology for antibody discovery and collaborates with IAVI (IAVI retains vaccine rights, Theraclone retinas therapeutic rights)
14. Monoclonal antibodies and 3BNC117 are being studied in combination, including the combination of their long-acting versions (LS) resistant escape variants have been shown to have cross resistance with PGT121 but remain sensitive to 3BNC117 and VRC01
VRC018
bNAb against gp120
For prevention
NIH P
Vicriviroc (MK-4176)
± MK-2048
IVR for PrEP10
Entry Inhibitor ± INI
NIH; Merck
Oral
Topical microbicide GS
bNAb against gp120
Gilead
PC-1005
(MIV-150+zinc acetate)
Multipurpose gel including for PrEP
NNRTI
Population Council; NIH
Other parenteral
Potential first-in-class
to reach market
Long-acting (LA) parenteral1 GS
(GS-CA1)
Capsid inhibitor
Gilead P
Being studied in adolescents and/or children
Medicines Patent Pool
List not exhaustive. Last updated on: 8/2018

2. HCV Direct-Acting Antivirals (DAAs)
Marketed or under active clinical development
Phase I
Phase II
Phase III
Marketed
AT-527
NS5B inhibitor - nuc
Atea Pharmaceuticals
Furaprevir
(TG-2349)
NS3/4A inhibitor
TaiGen
Ravidasvir 9
(PPI-668; ASC16; RDV)
NS5A inhibitor
Presidio  Pharco; Ascletis
Filed with CFDA
Ledipasvir
(GS-5885; LDV)
NS5A inhibitor
Gilead
Sofosbuvir
(GS-7977/PSI-7977; SOF)
NS5B inhibitor – nuc 2
Gilead
TD-6450
NS5A inhibitor
Theravance  TREKtx
Dasabuvir
(ABT-333)
NS5B inhibitor – non-nuc
AbbVie
Daclatasvir
(BMS ; DCV)
NS5A inhibitor
BMS
CC-31244
NS5B inhibitor – non-nuc
Cocrystal Pharma
Faldaprevir 7
(BI )
NS3/4A inhibitor
BI  TREKtx
Paritaprevir/r
(ABT-450/r)
NS3/4A inhibitor
Enanta + AbbVie
GSK
Oral & LAP
NS5B inhibitor – non-nuc
GSK
Ombitasvir
(ABT-267; OBV)
NS5A inhibitor
AbbVie
Grazoprevir
(MK-5172; GZR)
NS3/4A inhibitor
Merck
Elbasvir
(MK-8742; EBR)
NS5A inhibitor
Merck
MB-110
NS5A inhibitor
Microbio Co.
AL-335
NS5B inhibitor – nuc
Alios (now Janssen)
Asunaprevir 3
(BMS )
NS3/4A inhibitor
BMS
SH229
NS5B inhibitor
Nanjing Sanhome Pharmaceuticals
Odalasvir
(ACH-3102)
NS5A inhibitor
Achillion  Janssen
Velpatasvir
(GS-5816; VEL)
NS5A inhibitor
Gilead
Vaniprevir 4
(MK-7009)
NS3/4A inhibitor
Merck
Uprifosbuvir
(MK-3682; UPR)
NS5B inhibitor – nuc Merck
Voxilaprevir
(GS-9857; VOX)
NS3/4A inhibitor
Gilead
Sources: ClinicalTrials.gov; WHO ICTRP (international clinical trials registry platform)
Footnotes:
Based on in vitro anti-HCV activity as published. “Pangenotypic” as in effectiveness demonstrated for genotypes 1 – 6. Certain DAAs are referred to as “pangenotypic” by its originator but in vitro evidence for all six genotypes has not been publicly available. Occasionally multi-genotypic DAA (covering most but not all genotypes) may also be referred to misleadingly as “pangenotypic”, hence being differentiated here according to published in vitro evidence.
“Nuc” is short for NS5B nucleoside/nucleotide inhibitors, which are believed to have higher inherent barrier to resistance than non-nuc NS5B inhibitors
Asunaprevir was approved in Japan but US NDA has been withdrawn
4. MK-7009 was approved in Japan, but not by USFDA
ABT-493: its in vitro activity against GT5 has been “N/A” or not mentioned in publications so far. In ILC 2016, AbbVie preferred to it as pangenotypic DAA just like ABT-530. The combination is being studied across GT1-6
Danoprevir: requires ritonavir boosting. Early in vitro results published by InterMune suggested pangenotypic activity. Following a Phase 3 in China, Ascletis has filed danoprevir/r + PegIFN+RBV with the CFDA in Jan 2017 and received approval in June 2018 in China.
Faldaprevir had once reached Phase 3 in combination with PegIFN and RBV by BI for GT1, followed by BI withdrawing NDA. Now TREK Therapeutics has in-licensed worldwide rights and is studying this compound in combination with TD-6450 in Phase 2
GSK : Regulus and GKS had previously announced plans to combine long-acting parenteral (LAP) formulation of GSK with miRNA therapy RG-101 in Ph2 study, which however did not happen following RG-101’s discontinuation due to safety issues in June No new clinical study on GSK since 2015.
Ravidasvir is being studied by DNDi in combination with SOF, and separately by Ascletis in combination with danoprevir (+RBV). Ascletis has filed the ravidasvir with the CFDA in Aug 2018
Discontinued products:
In Aug 2014, Vertex announced its discontinuation of telaprevir production
In Jan 2015, Merck announced its withdrawal of boceprevir from market
On Sept 211, 017, Janssen announced that the development of triple regimen SIM+AL-335+odalasvir was discontinued. Further, Janssen has discontinued Phase 1 candidate AL611 after terminating the study
On Sept 29, 2017, Merck announced that the development of uprifosbuvir+ruzasvir+/-grazoprevir was also discontinued
On Dec 10, 2017, Medivir announced Jassen’s decision to terminate its simeprevir licence effective June This may signal discontinuation / withdrawal of SIM starting 2018.
Preclinical but may enter Ph1 soon (not yet found on clinical trials registry)
MK-8831: Described to be pangenotypic NS3/4A inhibitor but only published activity on GT1-3. Described as entering Ph1 in publication, but none found in clinical trial registry yet
MIV-802: NS5B nuc that Trek therapeutics acquired from Medivir
Discontinued9
Boceprevir
(SCH )
NS3/4A inhibitor
Merck
Ruzasvir
(MK-8408; RZR)
NS5A inhibitor
Merck
Pibrentasvir
(ABT-530; PIB)
NS5A inhibitor
AbbVie
Telaprevir
(VX-950)
NS3/4A inhibitor
Vertex  Janssen
NUC
Glecaprevir
(ABT-493; GLE) 5
NS3/4A inhibitor
Enanta + AbbVie
Individual pangenotypic potential per published in vitro data:1
Simeprevir
(TMC435; SIM; SMV)
NS3/4A inhibitor
Janssen
Pangenotypic coverage not verifiable
Pangenotypic
Not pangenotypic
Danoprevir/ritonavir 6
(ITMN-191, ASC08)
NS3/4A inhibitor
Roche; Ascletis
List not exhaustive. Host-targeting agents are not included
Medicines Patent Pool. Last updated on: 8/2018

3. HCV DAA Combination Regimens
Marketed
HCV DAA Combination Regimens
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Daclatasvir
(BMS )
NS5A
BMS
Ombitasvir
(ABT-267)
NS5A
AbbVie
Paritaprevir/r
(ABT-450/r)
NS3/4A
AbbVie
Dasabuvir
(ABT-333)
NS5B – non-nuc
AbbVie P P
GT1~4b
GT1 P
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Ledipasvir
(GS-5885)
NS5A
Gilead
GT1, 4, 5, 6;
+ RBV for GT3a
Ombitasvir
(ABT-267)
NS5A
Paritaprevir/r
(ABT-450/r)
NS3/4A P
± RBV for GT4
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Velpatasvir
(GS-5816)
NS5A
Gilead
Pibrentasvir
(ABT-530)
NS5A
AbbVie
Glecaprevir
(ABT-493)
NS3/4A
AbbVie P P
GT1~6f
GT1~6
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Velpatasvir
(GS-5816)
NS5A
Gilead
Voxilaprevir
(GS-9857)
NS3/4A
Gilead
GT1~6e
Elbasvir
(MK-8742)
NS5A
Merck
Grazoprevir
(MK-5172)
NS3/4A
Merck P
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Simeprevir
(TMC435)
NS3/4A
Janssen
± RBV GT1, 4;
+ SOF for GT3c +
GT1,
± RBV for GT1, 4d
Sources: ClinicalTrials.gov; WHO ICTRP (international clinical trials registry platform)
Footnotes:
a. SOF/LDV: EMA approved GT1, 3, 4 (GT3 only for cirrhotics as combination with RBV, 24w. But note 24w of SOF+RBV without LDV is an FDA-approved indication for GT3 already). FDA approved SOF+LDV for GT1, 4-6 and the addition of RBV is required in some cases of cirrhosis or liver transplant; also approved in children aged 12 & above weighing at least 35kg.
b. SOF+DCV: FDA approved GT1, 3. EMA approved DCV for GT1, 2, 3, 4, but recommending DCV+SOF specifically for GT1, 3, 4 (data on DCV+SOF for GT2 are considered limited). EASL had recommend SOF+DCV across GT1-6
c. GZR/EBR: GT1a testing for baseline NS5A RAVs required; GT3 approved in Canada only for EBV+GZR+SOF
d. SIM+SOF: FDA approved SIM+SOF only for GT1 (GT4 was for SIM+PEG+RBV). EMA approved SIM+SOF with or without RBV for GT1, 4. On Dec 10, 2017, Medivir announced Jassen’s decision to terminate its simeprevir licence effective June This may signal discontinuation / withdrawal of SIM starting 2018.
e. SOF/VEL/VOX: FDA approved for GT1-6 PLHCVs previously treated with any NS5A inhibitor, but only for GT1a and GT3 if previously treated with SOF without an NS5A inhibitor.
GLE/PIB: FDA approved for GT1-6 if treatment-naïve, or if previously treated with IFN, PegIFN, RBV and/or SOF; GT1 only, if previously treated with an NS5A inhibitor or NS3/4A inhibitor but not both
Ravidasvir + danoprevir/r + RBV was only studied in GT1 non-cirrhotic patients in Greater China
About Janssen DAA combinations:
AL-335+ODV (without SIM): during ILC2017, company announced “no plans for further evaluation” of this 2DAA combination for GT1 due to “inadequate efficacy” per Study AL There is a long-term follow-up study of patients who completed the study.
AL-335+ODV+SIM: company announced on Sept 11, 2017 the discontinuation of its further development
On Sept 29, 2017, Merck announced that the development of uprifosbuvir+ruzasvir+/-grazoprevir was also discontinued.
Sofosbuvir
(GS-7977)
NS5B – nuc
Gilead
Ravidasvir
(PPI-668; RDV)
NS5A
Presidio  Pharco, Ascletis +
Fixed-dose combination
Phase III P
FDA-approved for age 12+ P
Ravidasvir
(PPI-668; RDV)
NS5A
Presidio  Pharco, Ascletis
Danoprevir/ritonavir
(ITMN-191, ASC08)
NS3/4A inhibitor
Roche; Ascletis
Paediatric investigation underway +
+RBVg
Medicines Patent Pool
List not exhaustive. Last updated on: 8/2018

4. Development Progress of Paediatric HCV Regimens
Age 12+
Age 6 to <12 yrs
Age 3 to < 6 yrs
SOF + RBV
Approved
(GT2, 3; ≥35kg)
Phase 2 (GT2, 3)1
(small tablet or granules for young children)
SOF/LDV
(GT1, 4-6; ≥35kg)
Two Phase 2 studies
(1/2-dose tablet)
OBV/PTV/r ± DSV ± RBV
Phase 3
SOF/LDV + RBV
Phase 2 (GT3 only)
(Tablet or “age-appropriate dose or formulation”)
GRZ/EBR
Phase 2 (GT1, 4 only)
(Tablet or granules for young children)
SOF/VEL
Phase 2
(Tablet of “age-appropriate dose”)
SOF/VEL/VOX
May be covered in Registry for paediatric & adolescent patients
SOF + DCV
(Age 8-18, GT4 only, Egypt; 1 or ½ tablet)2 --
GLE/PIB
(“Paediatric formulation” for 3 to <12 yrs)
A separate Phase 2/3 study is ongoing at the National Liver Institute, Egypt, on SOF+RBV in children aged 10-18, n=41 only
Several Phase 3-4 studies on SOF+DCV by the Tehran University of Medical Sciences also enroll adolescents
Pangenotypic
Not pangenotypic
List not exhaustive. Some studies are investigator-initiated.
Medicines Patent Pool. Last updated 8/2018