Expansion of screening programmes and the increase in the diagnosis rate for HIV is expected to bolster the patient population available for treatment and thus drive the value of the anti-HIV product market worldwide, according to an HIV-AIDS industry report prepared by New York based Griffin Securities Inc.
The report said that the rapid growth in the HIV market had made it attractive to leading pharmaceutical companies, dominated by GlaxoSmithKline, Bristol-Myers Squibb, Merck & Co., Hoffman-La Roche, Pfizer (Agouron unit), Abbott Laboratories, Boehringer and Dupont Pharmaceuticals (currently be sold to Bristol-Myers Squibb).
Growth in the global HIV market is expected to create opportunities to expand sales for all the old players, particularly those marketing Nucleoside Analog Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), which have benefited from recent shifts in treatment patterns for HIV.
While the current therapies such as protease inhibitors and reverse transcriptase inhibitors have helped many patients with AIDS to manage their disease, these therapies are not curative, have significant, and often treatment-limiting, side effects and are extremely costly.
Salvage therapies should also have a positive impact on the value of the HIV market, which will involve the use of at least two Pls, at least two NNRTIs or an NNRTI and a PI. Also, to battle the development of growing resistance and declining immune responses, Griffin expects the addition of entry inhibitors and immune based adjunct therapies to existing drug regimens.
Newly diagnosed HIV positive patients are being infected with strains that are resistant to the existing therapies and triple therapy combinations. The relentless pursuit of next generation therapies to serve unmet needs, vaccines and cures should be advantageous for patients and the companies (both old and new) that are developing breakthroughs to address this drastic challenge.
The world should not underestimate the threat of AIDS. Everyday, more than 10,000 additional people around the world become infected with HIV. Twenty-two million people have died from the epidemic, with last year's three million death tolls, the highest yet.
There are currently 18 FDA approved anti-HIV drugs. They include Nucleoside and Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors. None of the currently approved drugs kill the HIV virus, but each class slows down the replicate of the virus in a particular way.
Nucleoside Analog Reverse Transcriptase Inhibitors (NRTIs or Nukes) from the backbone of every HIV HAART treatment regimen, with two drugs from this class generally included in every patient's drug combinations. NRTIs block reverse transcription (the creation of viral DNA from RNA) by providing "decoy" building blocks that interrupt the process. There are currently 8 FDA Approved Nucleoside Analogs. They are as follows:
- Zidovudine; AZT; Azidothymidine; Retrovir (GlaxoSmithKline);
- Didanosine; Dideoxyinosine; ddl; Videx (Bristol-Myers Squibb);
- Zalcitabine; Dideoxycytidine; ddC; Hivid (Hoffman-La Roche);
- Lamivudine; 3TC; Epivir (GlaxoSmithKline);
- Stavudine; 2', 3'-Didehydro-3'-deoxythymidine; D4T; Zerit (Bristol-Myers Squibb);
- Abacavir Succinate; 1592U89 Succinate; Ziagen ABC (GlaxoSmithKline);
- Combivir; lamivudine & zidovudine; (-)-3TC & AZT (GlaxoSmithKline); and
- Trizivir; abacavir & lamivudine & zidovudine; ABC & (-)-3TC & AZT (GlaxoSmithKline).
GlaxoSmithKline continues to be the strongest franchise in NRTIs and should maintain its position with its most recent entry, Trivizir, a three-in-one drug. In the near future, once-daily NRTI pipeline products from Triangle Pharmaceuticals (Corvivacil) and Gilead Sciences (Tenovir) should also benefit from their favourable once-daily dosing regimens.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs or non-nukes) are the newest class of anti-virals that have made a major impact on the global HIV market. NNRTIs interrupt reverse transcription, by binding to the reverse transcriptase enzyme and restricting its activity.
There are currently 3 FDA approved Non-Nucleoside Reverse Transcriptase Inhibitors. They are as follows: Nevirapine; BI-RG-587, Viramune (Boehringer); Delavirdine; BHAP; U-90152; Rescriptor (Pfizer Agouron Unit); and Efavirenz; DMP-266; Sustiva (DuPont / Merck).
DuPont's Sustiva is by far the market leader in NNRTIs. Pending FDA approval, DuPont's plans to launch a new tablet formulation (in 600 and 300 mg) of Sustiva, which will simplify therapy. Dupont is expected to close its sale of its pharmaceutical division to Bristol-Myers Squibb by the end of the year. With the addition of Dupont Pharmaceutical's lucrative franchises, such as Sustiva, Bristol-Myers Squibb's HIV market share should increase by about 3 to 5 per cent.
Other NNRTIs in human trials include: Emivirin (MKC-442, Coactinon) by Triangle Pharmaceuticals, capravine (AG1549) by Pfizer's Agouron unit, and TMC 120 by Tibotec Pharmaceutical.
Protease Inhibitors (PIs) are considered an extremely powerful class of anti-viral drugs, blocking the action of protease, an enzyme that cuts HIV protein chains into specific proteins needed to assemble a new copy of the virus.
The high dosage levels associated with PIs however, are a negative factor, as is their relatively poor side effect profile. Merck's Crixivan and Pfizer's Viracept continue to be the standard of care in this class. In addition, Abbott Laboratories' Kaletra is coming on strong.
There are currently seven FDA approved Protease Inhibitors which are as follows:
Saquinavir; Ro 31-8959; Fortovase; Invirase (Hoffman-La Roche); Indinavir; MK639; L-735, 524; Crixivan (Merck); Ritonavirl ABT-538; Norvir (Abbott Laboratories); Nelfinavir; Viracept; AG-1343 (Pfizer / Agouron unit); Amprenavir; Agenerase; VX-478; 141W94 (GlaxoSmithKline); Lopinavir; ABT-378; Aluviran; Component of Kaletra (Abbott Laboratories); and Kaletra; lopinavir & ritonavir; ABT-378 & ABT-538; Aluviran & Norvir (Abbott Laboratories).
Companies that are now working to develop protease drugs that are more potent and easier to take include: BMS232632 by Bristol-Myers Squibb; tripanavir by Boehringer Ingelheim; and Mozenavir (DMP-450) by Triangle Pharmaceuticals.
The new class of anti-HIV products called entry or attachment inhibitors are progressing positively, however, none have been approved yet. Several are in human trials, including: Roche's/Trimeris' fusion inhibitor T-20 (Pentafuside) and T-1249; PRO 452 by Progenics Pharmaceuticals Inc; SCH -1 by Schering Plough; and HIV-Hemopurifier by Aethlon Medical.
Griffin's expects immune-based therapy to play an increasing role in the near future. The immune modulators are designed to help the efforts of one or more of the so-called armies of the immune system: antibodies; natural killer cells; killer T cells; and helper T cells.
In addition, the immune modulators may also prove effective at flushing out latent virus that remain hidden in many cells and lymphoid tissues of the body (and virtually undetected in the blood). This reservoir of latent cells is believed to be one of the major barriers to completely eliminating HIV from a person's body.
Companies that are currently pursuing various immune therapy strategies include: Interleukin 2 (IL-2, Aldesleukin, Proleukin by Chiron Corporation; HE2000 by Hollis-Eden Pharmaceuticals, Multikine by Cel-Sci; and the HIV-Hemopurifier by Aethlon Medical.
Finally, whilst the scientific knowledge of HIV is limited, the goal of developing an HIV vaccine is an area of great interest. Several companies are pursuing various strategies to prevent infection by the HIV, rather than just treat the established virus, including AIDSVAX by VaxGen, the closest to FDA approval.
The FDA will require patients to achieve a 30 per cent greater reduction in HIV infections versus their placebo counterparts. Recent failures serve as a painful reminder of the difficulties and risks associated with vaccine development. Also continuing research and development of vaccines is HGP-30 and HGP-30W by Cel-Sci, ALVAC 1452 by Aventis Pasteur; TGAAC-09 by Targeted Genetics; TBC-2B by Therion Biologics; and other entrants by Merck, GlaxoSmithKline and Chiron. An approval by any of these companies could represent a home run for the company that delivers the vaccines and a critical breakthrough for the AIDS community at large.