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When Could Gilead Have Released TAF?

Posted by Neil Shouse | Jul 01, 2019 | 0 Comments

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While it has not yet been proven, it seems that Gilead Sciences, Inc. had the ability to bring safer, TAF-based versions of its HIV pills to the market up to a decade earlier than they actually did. Victims who took the more dangerous, TDF-based versions of the pills and who have suffered from their severe side effects have filed mass tort claims against Gilead for their losses.

What are TDF and TAF HIV drugs?

Gilead Sciences, Inc. has manufactured numerous pills for HIV treatment. Some are based on the drug tenofovir disoproxil fumarate, or TDF, including the brand name pills:

  • Cimduo,
  • Stribild,
  • Atripla,
  • Truvada,
  • Complera,
  • Symfi-Lo, and
  • Viread.

Newer treatments, however, are based on the drug tenofovir alafenamide fumarate, or TAF, including the brand names:

  • Genvoya,
  • Descovy,
  • Vemlidy, and
  • Odefsey.

Different brand names signify different drug “cocktails.” For example, the TDF-based drug Stribild has a total of four drugs in it:

  1. Elvitegravir,
  2. Cobicistat,
  3. Emtricitabine, and
  4. TDF.

Newer, TAF-based versions of these pills merely replace the active ingredient TDF with the newer drug TAF. For example, Genvoya, the drug that replaces Stribild, is comprised of:

  1. Elvitegravir,
  2. Cobicistat,
  3. Emtricitabine, and
  4. TAF.

Only one drug is comprises solely of TDF, Viread, and it was replaced by Vemlidy, which is comprised solely of TAF.

Are TAF drugs safer than TDF drugs?

Yes. Numerous medical studies and clinical trials have shown that TAF-based HIV drugs are less toxic and safer to take than HIV drugs that are based on TDF. In particular, TDF-based HIV drugs can cause:

  • Bone loss,1
  • Kidney damage,2 and
  • Lactic acidosis.3

TAF-based HIV drugs either do not present these dangers, or carry far lower risks.

For example, there are three studies conducted in 2014 and 2015 that compared bone loss in 2,068 people taking either a TDF-based drug or the TAF-based pill, Genvoya.4 After 48 weeks, these studies found bone loss in patients taking a TDF-based drug was far higher than in those people taking Genvoya in both their hip and in their spine:

 

Patients Taking TDF-Based Drugs

Patients Taking TAF-Based Genvoya

Percentage of Bone Loss in the Hip

2.4% to 3.8%

0.6% to 0.8%

Percentage of Bone Loss in the Lumbar Spine

2.9% to 3.6%

1.0% to 1.6%

When did Gilead begin developing TAF-based drugs for HIV treatment?

Gilead was developing TAF as a safer alternative to TDF as early as April 2001. That was when scientists at Gilead published an article on TAF toxicity in dogs.5 The experiments conducted for these studies found that TAF was far more effective than TDF, meaning it could be administered at far lower doses and reduce the dangers of its toxicity.

Of course, Gilead could have been researching and developing TAF-based HIV treatments well before this point.

When could Gilead have released TAF-based HIV treatments?

It is unclear when Gilead could have released its TAF line of HIV treatments because, in 2004, they stopped developing the new drug for nearly ten years.

Lawsuits filed by victims claim that Gilead put TAF development on hold “because TDF sales were booming and Viread had begun to corner the market in antiviral treatments for HIV.”6 By withholding TAF-based drugs, it allowed Gilead to reap the profits it would make over its entire period of exclusive rights to sell TDF-based HIV treatments. By withholding the safer, TAF-based versions of these drugs, it would allow Gilead to release TAF treatments just as its TDF ones were beginning to face market competition from generics.7 Market analysts estimated that such a move would have made Gilead billions of dollars.8

Gilead, meanwhile, claims that their movement away from TAF was purely a business decision: They shifted money away from TAF research and into integrase inhibitors – another type of HIV treatment.9

A timeline of Gilead's development of TAF and TDF treatments

Whether Gilead withheld its safer TAF versions of its HIV treatments or not will make a huge difference in the lawsuits currently pending against the pharmaceutical company. The timeline of its development of TAF and TDF drugs paints a damning picture against the company:

  • 1984: The drug tenofovir is discovered in Europe,
  • 1985: Tenofovir is found to contain HIV cells,
  • 1991: Gilead acquires rights to tenofovir from the European labs that discovered it,
  • 1990s: Gilead researches and develops HIV treatments from tenofovir, including TDF and TAF,
  • April 2001: Gilead scientists publish article that found that TAF is less toxic in animals, and so could be administered in lower doses, which would have the same efficacy but with fewer side effects as TDF,10
  • October 2001: Gilead receives approval from the U.S. Food and Drug Administration (FDA) for its first TDF-based HIV treatment, Viread,11
  • March 14, 2002: The FDA warns Gilead that it cannot claim its TDF-based drugs have “no toxicities” or that they are a “miracle drug,” and cannot claim the boxed warning concerning lactic acidosis is a “class effect warning,”12
  • April 2, 2002 – January 22, 2003: Gilead pays doctors to conduct clinical trials on TAF. Those studies find that TAF is less toxic and safer than TDF-based HIV treatments, but will not be published until 2014,13
  • July 29, 2003: The FDA again warns Gilead that it cannot downplay the side effects listed on the warning labels of its drugs or claim that they are “benign,”14
  • August 2, 2004: The FDA approves Truvada, another TDF-based HIV pill,15
  • October 2004: Gilead announces that it conducted an “internal business review” and would discontinue its research and development into TAF, covering up the medical studies it had conducted in the process,16
  • October 2004 – May 2005: Gilead obtains seven patents related to the development of TAF,17
  • July 2006: The FDA approves another TDF-based drug, Atripla,18
  • 2010: Gilead announces that it has discovered an “interesting new molecule” that could be used in HIV treatment – TAF,19
  • 2010 – 2014: Gilead continues to develop TAF,
  • August 2011: The FDA approves another TDF-based drug, Complera,20
  • August 2012: The FDA approves another TDF-based drug, Stribild,21
  • February 6, 2014: Clinical TAF trials conducted in 2002 and 2003 are published,22
  • November 2015: The FDA approves the first TAF-based HIV drug, Genvoya, to replace Stribild,23
  • November 2015: Gilead begins urging doctors to switch their patients from TDF-based drugs to TAF-based drugs, claiming that TDF drugs are highly toxic and present risks of kidney damage, lactic acidosis, and bone loss,
  • March 2016: The FDA approves another TAF-based HIV drug, Odefsey, to replace Complera,24
  • April 2016: Another TAF-based HIV drug, Descovy, is approved by the FDA to replace Truvada,25
  • December 15, 2017: Viread, the first TDF-based HIV pill, became available in generic form,
  • February 2018: The FDA approves two more TDF-based drugs; Symfi-Lo,26 and Cimduo,27
  • May 8, 2018: Lawsuits filed against Gilead for withholding safer TAF drugs and forcing patients to continue to suffer from TDF's severe side effects,28
  • November 4, 2020: Generics for Complera and Truvada become available,
  • October 4, 2032: Generic versions of Stribild become available.

References:

  1. Iwen F Grigsby, Lan Pham, Louis M Mansky, Raj Gopalakrishnan, and Kim C Mansky, “Tenofovir-associated bone density loss,” Therapeutics and Clinical Risk Management 6:41-7 (2010).

  2. Willem D.F. Venter, June Fabian, and Charles Feldman, “An overview of tenofovir and renal disease for the HIV-treating clinician,” South African Journal of HIV Medicine 19(1):817 (2018).

  3. Pablo Rivas, Jorge Polo, Miguel de Górgolas, Manuel L Fernández Guerrero, “Drug points: Fatal lactic acidosis associated with tenofovir,” British Medical Journal 327:711 (2003).

  4. Sax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, et al., “Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study,” Journal of Acquired Immune Deficiency Syndromes 67(1):52-8 (September 1, 2014), Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, et al., “Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials,” Lancet 385(9987):2606-15 (June 27, 2015), and Mills A, Crofoot G Jr, McDonald C, Shalit P, “Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate in the First Protease Inhibitor-Based Single-Tablet Regimen for Initial HIV-1 Therapy: A Randomized Phase 2 Study,” Journal of Acquired Immune Deficiency Syndromes 69(4):439-45 (August 1, 2015).

  5. Lynch T, Eisenberg G, Kernan M, “LC/MS determination of the intracellular concentration of two novel aryl phosphoramidate prodrugs of PMPA and their metabolites in dog PBMC,” Nucleosides, Nucleotides, and Nucleic Acids 20(4-7):1415-19 (April – June, 2001).

  6. Complaint at 3, Martinez v. Gilead Sciences, Inc., No. BC 705063 (Cal. filed May 8, 2018).

  7. Melody Petersen, “Patients sue Gilead, saying drug company intentionally delayed safer HIV medicine,” Los Angeles Times (May 9, 2018).

  8. Melody Petersen, “A question of timing: A lawsuit claims Gilead Sciences could have developed a less-harmful version of its HIV treatment sooner,” Los Angeles Times (May 29, 2016).

  9. See note 8.

  10. See note 5.

  11. FDA Approval Letter for Viread.

  12. FDA Warning Letter to Gilead Sciences, Inc. – March 14, 2002.

  13. Markowitz M, et al., “Phase I/II study of the pharmacokinetics, safety and antiretroviral activity of tenofovir alafenamide, a new prodrug of the HIV reverse transcriptase inhibitor tenofovir, in HIV-infected adults,” Journal of Antimicrobial Chemotherapy 69(5):1362-69 (February 6, 2014).

  14. FDA Warning Letter to Gilead Sciences, Inc. – July 29, 2003.

  15. FDA Approval Letter for Truvada.

  16. See note 7.

  17. Complaint at 4, Martinez v. Gilead Sciences, Inc., No. BC 705063 (Cal. filed May 8, 2018).

  18. FDA Approval Letter for Atripla.

  19. See note 7.

  20. FDA Approval Letter for Complera.

  21. FDA Approval Letter for Stribild.

  22. See note 13.

  23. FDA Approval Letter for Genvoya.

  24. FDA Approval Letter for Odefsey.

  25. FDA Approval Letter for Descovy.

  26. FDA Approval Letter for Symfi-Lo.

  27. FDA Approval Letter for Cimduo.

  28. See note 6.

About the Author

Neil Shouse

Southern California DUI Defense attorney Neil Shouse graduated with honors from UC Berkeley and Harvard Law School (and completed additional graduate studies at MIT).

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