Medications Under Development- Updated April, 2007

New Medications Under Development (Updated 10/05)

New Medications Under Development

 

In the Pipeline

 

You will hear the term “In the pipeline” on occasion; this term in relation to HIV is used to describe new medications that are under development and not yet available by prescription (FDA approved). Whether or not these drugs medications are approved remains to be seen. Some of these medications may be available through “Clinical Trials,” “Compassionate Use (in salvage situations)” and “Expanded access” (just prior to approval).

 

NRTI’s Under development

 

  • Alovudine (MIV-310, FLT) – Boehringer Inglheim
    • Seems effective against HIV resistant to other NRTI’s
    • Seems to have the same toxicities as AZT & d4T, i.e. liver, anemia, bone marrow – should not use together
    • Phase II (AIDS Infonet ,2004, fact sheet 410)

 

  • Reverset (NRTI) Pharmasset, Inc. & Incyte 3
    • potent in vitro activity against many resistant strains of HIV w/few side effects
    • unlikely to act against the Q151M or 69 insertion mutants
    • After short-term studies seems to effectively lower viral load & increase t-cells
    • Phase 2 & 3 studies – QD (once a day) – 50,100,200mg (Youle MD, NATAP, 2004) (AIDS Infonet ,2004, fact sheet 410)

 

 

  • SPD-754 (NRTI) – Shire Pharmaceuticals
    • Shows good activity against 3TC (Epivir) resistant strains
    • Seems well tolerated with strong activity against HIV
    • Phase II trials
    • Related compound SPD756 Phase I
    • Seems no mitochondrial toxicity – good synergy with other antivirals – 6 fold with 3TC (Youle MD, NATAP, 2004)

 

 

  • Elvucitabine (ACH-126,443, Fd4C) – Achillion Pharmaceuticals
    • QD dosing – and seems to be active against HIV resistant to other NRTI’s
    • Also seems active against Hep B
    • 100 & 50mg caused bone marrow suppression – halted – lower doses will be tested (AIDS Infonet ,2004, fact sheet 410)

 

 

  • Elvucitabine (ACH-126,443, Fd4C) – Achillion Pharmaceuticals
    • QD dosing – and seems to be active against HIV resistant to other NRTI’s
    • Also seems active against Hep B
    • 100 & 50mg caused bone marrow suppression – halted – lower doses will be tested (AIDS Infonet ,2004, fact sheet 410)

 

  • MIV-210 (FLG) – GlaxoSmithKline
    • Seems to show good activity against HIV resistant to other NRTI’s
    • Phase I (AIDS Infonet ,2004, fact sheet 410)

 

NRTI’s halted development

 

  • Adefovir – Gilead
  • DAPD – Gilead
  • Dotc (BCH-10652, BCH-10618) – BioChem Pharma
  • FddA – US Bioscience
  • GW420867X – GlaxoSmithKline
  • Lobucavir – Bristol-Myers Squibb

 

NNRTI’s Under development

 

  • Capravirine (AG1549, formerly S-1153) Agouron Pharmaceuticals
    • Seems 10 stronger than NV or DL against wt virus
    • Needs 2 to 3 mutations to become resistant
    • Phase III – some toxicity problems

 

  • Calanolide A – Sarawak MediChem Pharmaceuticals
    • Rain Forest plant derivative that easily crosses blood-brain barrier
    • Seems synergistic w/other HIV meds (Sarawak MediChem, 2000)
    • Good half-life and seems to be active against HIV resistant to other NNRTI’s
    • Phase II (AIDS Infonet ,2004, fact sheet 430)

 

 

  • GW678248 and GW695634 (NNRTIs) sulfonamide + pro - GlaxoSmithKline
    • Seems to work well against HIV resistant to other NNRTI’s (Youle MD, NATAP, 2004)
    • Seems to be well tolerated with few adverse events

 

 

  • GW5634 – NNRTI – GlaxoSmithKline
    • Pro drug of GW8248
    • Highly active against HIV in lab
    • Phase I (AIDS Infonet ,2004, fact sheet 430)

 

  • MIV-150 – Medivir & Chiron
    • Laboratory test look good against HIV resistant to other NNRTI’s
    • Should take a long time to become resistant
    • Phase II (AIDS Infonet ,2004, fact sheet 430)

 

 

  • Racivir – Pharmasset, Inc.
    • Excellent half life – seems to have good activity against HIV
    • Seems to have activity against Hep B
    • Possible qd (AIDS Infonet ,2004, fact sheet 410)

 

  • TMC 125 (NNRTI) Tebotec – Phase II & III
    • Seems to have some activity against HIV resistant to other NNRTI’s
    • It may take longer to develop resistance; however there may be some cross resistance (Youle MD, NATAP, 2004) (AIDS Infonet ,2004, fact sheet 430)

 

NNRTI’s stopped development

 

  • Atevirdine – Upjohn
  • BILR355 – Boehringer Ingelheim
  • DPC083 – Bristol-Myers Squibb
  • Emivirine – Triangle
  • Loviride – Janssen
  • HBY-097 – Hoechst-Bayer
  • PNU142721 – Pharmacia & Upjon
  • TMC-120 - Tibotec

 

 

PI’s under development

 

  • TMC 114 – Tibotec
    • Boosted w/ritonavir
    • Rapid VL (viral load- amount of virus in the blood) drop
    • Seems to be effective against HIV resistant to other PI’s w/3 PI mutations
    • Main side effects seem to be diarrhea, gas, headache and dizziness
    • Phase II (AIDS Infonet ,2004, fact sheet 440) (Youle MD, NATAP, 2004)

 

  • GW640385 (aka VX-385)– GlaxoSmithKline & Vertex
    • Seems very effective against both wt and HIV resistant mutants
    • Low dose may mean lower side effects (currently no sever side effects)
    • Most likely boosted with ritonavir
    • Phase I (AIDS Infonet ,2004, fact sheet 440)

 

  • RO033-4649 – Roche
    • Seems effective against HIV resistant to other PI’s
    • Phase I (AIDS Infonet ,2004, fact sheet 440)

PI’s halted development

 

  • L-756,423 – Merck
  • Mozenavir (DMP450) – Triangle

 

Fusion and Entry inhibitors under Development

 

  • GW873140 (CCR5 receptor antagonist) – GlaxoSmithKline
    • Binds tightly to CCR5
    • Few side effects –mild abdominal cramping, diarrhea, nausea
    • May be less likely to build resistance than other 2 drugs in this class
    • BID dosing
    • Phase I (Youle MD, NATAP, 2004) DISCONTINUED

 

  • SCH-D (CCR5 receptor antagonist) – Shering-Plough – CCR5 antagonist
    • Showed better bioavailability
    • BID dosing
    • Appears difficult to select resistance virus – should have good durability
    • No significant toxicity (Youle MD, NATAP, 2004) DISCONTINUED

 

 

  • PRO-140 & PRO-542 – Progenics
  • PRO-140 – Phase I - resistance to PRO 140 does not develop rapidly - PRO 140 is a monoclonal antibody that binds to CCR5 – few side effects
  • PRO-542 – Phase II – PRO 542 directly neutralizes HIV (virus attaches to med instead of CD4), thereby preventing the attachment of the virus to CD4 (Moore, BioSpace Beat, nd) (AIDS Meds.com, 2003)

 

 

  • BMS-488043 (attachment inhibitor) – Bristol Myers Squibb – Phase I/II
    • Prevents a structure on HIV's surface - gp120 - from attaching to the human cell's CD4 receptor
    • Non-toxic – no cross resistance
    • Very mild headache and fatigue
    • (Brown, 2004)

 

 

  • TNX-355 – Tanox – monoclonal antibody – Blocks CD4 receptor
    • IV (in vain) twice-monthly
    • Phase II
    • No significant side effects
    • Best used with good background antivirals (BioHouston News Letter, 2004)

 

  • UK-427,857 – Pfizer – CCR5 antagonist – Oral
    • Dose not known yet
    • Phase I
    • Not much known about side effects
    • Will most likely need to be used in combination with other anti-HIV drugs (AIDS Meds.com, 2003)

 

 

Novel Drugs Under Development

 

  • Microbicides – Topical – inter-vaginal/anal
  • Zinc Finger – zinc injectors break apart nucleocapsid
  • Integrase inhibitors – prevent integration (connecting) of viral DNA to t-cell DNA
  • Antisense Drugs – mirrow image of HIV genetic code – prevents HIV from functioning
  • (AIDS Infonet ,2004, fact sheet 460)

 

References:

 

 

 

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