Dupont Pharmaceuticals Submits New Drug Application for One Tablet, Once-Daily Formulation of Sustiva(TM)

Apr 04, 2001, 01:00 ET from DuPont Pharmaceuticals Company

    WILMINGTON, Del., April 4 /PRNewswire/ -- DuPont Pharmaceuticals Company
 today announced it has submitted a new drug application to the U.S. Food and
 Drug Administration (FDA) for both a 600 and 300 mg tablet formulation of its
 anti-HIV drug Sustiva(TM) (efavirenz).
     Sustiva is a once-daily non-nucleoside reverse transcriptase inhibitor
 (NNRTI) used in combination treatment for HIV.  The new formulation will
 provide patients with the option to take one 600 mg Sustiva tablet once daily
 instead of the currently approved three 200 mg capsules once daily.  The
 600 mg tablet is approximately the same size as a Sustiva 200 mg capsule.
     "The new tablet formulation, which will work the same way as our currently
 approved capsule, will simplify therapy and may help patients better adhere to
 their anti-HIV treatment," said Tim Ravenscroft, Senior Vice President,
 Virology, DuPont Pharmaceuticals.  "Compared to the other HIV drugs
 recommended by the U.S. Department of Health and Human Services
 (DHHS - Column A) which need between 6 and 10 pills per day, Sustiva will only
 require one tablet per day.  In addition to providing potent and durable
 treatments for HIV, we're committed to helping find new ways to make taking
 these treatments easier for patients.  This new tablet helps achieve that
 goal."
     Pending FDA approval, DuPont Pharmaceuticals hopes to launch the 600 and
 300 mg formulations in early 2002 and will continue to manufacture the 200 mg
 capsules for those who still wish to take Sustiva as three capsules once-
 daily.
     Data recently presented at the 8th Conference on Retroviruses and
 Opportunistic Infections* by Margaret Fischl, M.D., University of Miami,
 comparing directly observed therapy (DOT) to self-administered therapy (SAT)
 showed that SAT with a regimen containing Sustiva plus nucleoside reverse
 transcriptase inhibitors (NRTIs) was almost as effective as DOT.  Overall,
 100 percent of patients receiving DOT responded and 94 percent of patients
 receiving Sustiva plus 2 NRTIs in the SAT group responded through 48 weeks.
 Patients who received SAT regimens including a protease inhibitor plus NRTIs
 responded at a lower rate.  These data indicate the benefits of simple, but
 potent, regimens.  Patients in this study took three 200 mg capsules of
 Sustiva once-daily.
     Based on these data, it appears that a self-administered regimen including
 three Sustiva capsules provides better results, which may be attributed to
 better adherence.  The new 600 mg single daily tablet has the potential to
 further improve adherence and therapy success for people living with HIV.
     Results of a recent adherence survey** indicate that approximately
 60 percent of HIV-positive patients find it difficult to adhere to their
 antiretroviral regimen.  Some of the reasons associated with this difficulty
 include too many pills (67 percent), side effects (61 percent), food
 restrictions (55 percent) and frequency of having to take the pills
 (49 percent).  The availability of Sustiva as one or two pills per day as part
 of a combination regimen may help patients cut down the number of pills
 required per day.
     In February 2001, the U.S. Department of Health and Human Services (DHHS)
 continued to list for the second year in a row Sustiva as the only non-
 nucleoside reverse transcriptase inhibitor "strongly recommended" for use in
 first-line combination with NRTIs for the treatment of HIV-infected
 individuals.
     Sustiva is generally well tolerated.  The most common adverse events are
 nervous system symptoms (e.g., dizziness, insomnia, impaired concentration,
 somnolence, and abnormal dreaming) and mild to moderate rash.  These symptoms
 occur early in treatment and generally resolve within two to four weeks.  In a
 small number of patients, serious psychiatric adverse experiences have been
 reported.  In controlled trials, serious psychiatric symptoms observed were
 severe depression (0.9%), suicidal ideation or attempts (0.5%), aggressive
 behavior (0.3%), paranoid reactions (0.2%) and manic reactions (0.1%).  These
 problems were seen at a similar frequency in control groups and tended to
 occur more often in patients with a history of mental illness, where the
 frequency of each of these events was approximately one percent.  A few
 suicides have been reported; however, a causal relationship to Sustiva has not
 been established.  Patients with serious psychiatric experiences should
 contact their physician.  Women should not become pregnant while taking
 Sustiva because birth defects have been seen in animals given Sustiva.
 Patients should be cautioned not to operate hazardous machinery or drive if
 they experience nervous system symptoms.
     Sustiva is administered as three 200 mg capsules once-daily.  Sustiva
 should not be administered concurrently with Hismanal(R) (astemizole),
 Propulsid(R) (cisapride), Versed(R) (midazolam), Halcion(R) (triazolam) or
 ergot derivatives.  Current treatment guidelines recommend against the use of
 any antiretroviral agent as monotherapy.  Therefore, Sustiva must not be used
 as a single agent to treat HIV or added on as a sole agent to a failing
 regimen.  The choice of new antiretroviral agents to be used in combination
 with Sustiva should take into consideration the potential for viral cross-
 resistance.  Sustiva therapy should always be initiated in combination with at
 least one other antiretroviral agent to which the patient has not been
 previously exposed.
     DuPont Pharmaceuticals Company, a wholly owned subsidiary of DuPont, is a
 worldwide business focused on research, development and delivery of
 pharmaceuticals and imaging agents to treat unmet medical needs in the fights
 against HIV/AIDS, cardiovascular disease, inflammatory diseases, cancer and
 neurological diseases.
     DuPont (NYSE:   DD) is a science company, delivering science-based solutions
 that make a difference in people's lives in food and nutrition; health care;
 apparel; home and construction; electronics; and transportation.  Founded in
 1802, the company operates in 70 countries and has 93,000 employees.
     For full Sustiva prescribing information, please visit the company's
 Website at www.sustiva.com or call 1-800-4PHARMA (1-800-474-2762).
 
     Sustiva(TM) is a trademark of DuPont Pharmaceuticals Company.
 
     The other brands listed are the registered trademarks of their respective
 owners and are not the trademarks of DuPont Pharmaceuticals.
 
     *Impact of Directly Observed Therapy on Long-Term Outcomes in HIV Clinical
 Trials, M. Fisch1, J. Castro, R. Monroig, E. Scerpella, L. Thompson, D.
 Rechtine, and D. Thomas, 8th Conference on Retroviruses and Opportunistic
 Infections, Abstract #528, February 2001
 
     **The Survey on Treatment Adherence by HIV+ People was managed and
 tabulated by Savitz Research, Chicago, and fielded through a written
 questionnaire by National Family Opinion (NFO), which has a databank of
 self-identified HIV+ individuals, and via the Internet to a Greenfield Online
 databank of survey volunteers.
 
 

SOURCE DuPont Pharmaceuticals Company
    WILMINGTON, Del., April 4 /PRNewswire/ -- DuPont Pharmaceuticals Company
 today announced it has submitted a new drug application to the U.S. Food and
 Drug Administration (FDA) for both a 600 and 300 mg tablet formulation of its
 anti-HIV drug Sustiva(TM) (efavirenz).
     Sustiva is a once-daily non-nucleoside reverse transcriptase inhibitor
 (NNRTI) used in combination treatment for HIV.  The new formulation will
 provide patients with the option to take one 600 mg Sustiva tablet once daily
 instead of the currently approved three 200 mg capsules once daily.  The
 600 mg tablet is approximately the same size as a Sustiva 200 mg capsule.
     "The new tablet formulation, which will work the same way as our currently
 approved capsule, will simplify therapy and may help patients better adhere to
 their anti-HIV treatment," said Tim Ravenscroft, Senior Vice President,
 Virology, DuPont Pharmaceuticals.  "Compared to the other HIV drugs
 recommended by the U.S. Department of Health and Human Services
 (DHHS - Column A) which need between 6 and 10 pills per day, Sustiva will only
 require one tablet per day.  In addition to providing potent and durable
 treatments for HIV, we're committed to helping find new ways to make taking
 these treatments easier for patients.  This new tablet helps achieve that
 goal."
     Pending FDA approval, DuPont Pharmaceuticals hopes to launch the 600 and
 300 mg formulations in early 2002 and will continue to manufacture the 200 mg
 capsules for those who still wish to take Sustiva as three capsules once-
 daily.
     Data recently presented at the 8th Conference on Retroviruses and
 Opportunistic Infections* by Margaret Fischl, M.D., University of Miami,
 comparing directly observed therapy (DOT) to self-administered therapy (SAT)
 showed that SAT with a regimen containing Sustiva plus nucleoside reverse
 transcriptase inhibitors (NRTIs) was almost as effective as DOT.  Overall,
 100 percent of patients receiving DOT responded and 94 percent of patients
 receiving Sustiva plus 2 NRTIs in the SAT group responded through 48 weeks.
 Patients who received SAT regimens including a protease inhibitor plus NRTIs
 responded at a lower rate.  These data indicate the benefits of simple, but
 potent, regimens.  Patients in this study took three 200 mg capsules of
 Sustiva once-daily.
     Based on these data, it appears that a self-administered regimen including
 three Sustiva capsules provides better results, which may be attributed to
 better adherence.  The new 600 mg single daily tablet has the potential to
 further improve adherence and therapy success for people living with HIV.
     Results of a recent adherence survey** indicate that approximately
 60 percent of HIV-positive patients find it difficult to adhere to their
 antiretroviral regimen.  Some of the reasons associated with this difficulty
 include too many pills (67 percent), side effects (61 percent), food
 restrictions (55 percent) and frequency of having to take the pills
 (49 percent).  The availability of Sustiva as one or two pills per day as part
 of a combination regimen may help patients cut down the number of pills
 required per day.
     In February 2001, the U.S. Department of Health and Human Services (DHHS)
 continued to list for the second year in a row Sustiva as the only non-
 nucleoside reverse transcriptase inhibitor "strongly recommended" for use in
 first-line combination with NRTIs for the treatment of HIV-infected
 individuals.
     Sustiva is generally well tolerated.  The most common adverse events are
 nervous system symptoms (e.g., dizziness, insomnia, impaired concentration,
 somnolence, and abnormal dreaming) and mild to moderate rash.  These symptoms
 occur early in treatment and generally resolve within two to four weeks.  In a
 small number of patients, serious psychiatric adverse experiences have been
 reported.  In controlled trials, serious psychiatric symptoms observed were
 severe depression (0.9%), suicidal ideation or attempts (0.5%), aggressive
 behavior (0.3%), paranoid reactions (0.2%) and manic reactions (0.1%).  These
 problems were seen at a similar frequency in control groups and tended to
 occur more often in patients with a history of mental illness, where the
 frequency of each of these events was approximately one percent.  A few
 suicides have been reported; however, a causal relationship to Sustiva has not
 been established.  Patients with serious psychiatric experiences should
 contact their physician.  Women should not become pregnant while taking
 Sustiva because birth defects have been seen in animals given Sustiva.
 Patients should be cautioned not to operate hazardous machinery or drive if
 they experience nervous system symptoms.
     Sustiva is administered as three 200 mg capsules once-daily.  Sustiva
 should not be administered concurrently with Hismanal(R) (astemizole),
 Propulsid(R) (cisapride), Versed(R) (midazolam), Halcion(R) (triazolam) or
 ergot derivatives.  Current treatment guidelines recommend against the use of
 any antiretroviral agent as monotherapy.  Therefore, Sustiva must not be used
 as a single agent to treat HIV or added on as a sole agent to a failing
 regimen.  The choice of new antiretroviral agents to be used in combination
 with Sustiva should take into consideration the potential for viral cross-
 resistance.  Sustiva therapy should always be initiated in combination with at
 least one other antiretroviral agent to which the patient has not been
 previously exposed.
     DuPont Pharmaceuticals Company, a wholly owned subsidiary of DuPont, is a
 worldwide business focused on research, development and delivery of
 pharmaceuticals and imaging agents to treat unmet medical needs in the fights
 against HIV/AIDS, cardiovascular disease, inflammatory diseases, cancer and
 neurological diseases.
     DuPont (NYSE:   DD) is a science company, delivering science-based solutions
 that make a difference in people's lives in food and nutrition; health care;
 apparel; home and construction; electronics; and transportation.  Founded in
 1802, the company operates in 70 countries and has 93,000 employees.
     For full Sustiva prescribing information, please visit the company's
 Website at www.sustiva.com or call 1-800-4PHARMA (1-800-474-2762).
 
     Sustiva(TM) is a trademark of DuPont Pharmaceuticals Company.
 
     The other brands listed are the registered trademarks of their respective
 owners and are not the trademarks of DuPont Pharmaceuticals.
 
     *Impact of Directly Observed Therapy on Long-Term Outcomes in HIV Clinical
 Trials, M. Fisch1, J. Castro, R. Monroig, E. Scerpella, L. Thompson, D.
 Rechtine, and D. Thomas, 8th Conference on Retroviruses and Opportunistic
 Infections, Abstract #528, February 2001
 
     **The Survey on Treatment Adherence by HIV+ People was managed and
 tabulated by Savitz Research, Chicago, and fielded through a written
 questionnaire by National Family Opinion (NFO), which has a databank of
 self-identified HIV+ individuals, and via the Internet to a Greenfield Online
 databank of survey volunteers.
 
 SOURCE  DuPont Pharmaceuticals Company