Roche and Trimeris to Discontinue "Biojector 2000" Device for Enfuvirtide (Fuzeon)

Roche and Trimeris announced on October 3 that they would no longer seek approval of the "Biojector 2000" device as an alternative to standard needles and syringes for the administration of the HIV-1 entry inhibitor enfuvirtide (Fuzeon; T-20).

The companies attributed the discontinuation in part to "a significant delay in achieving U.S. regulatory approval due to the time required to generate additional data."

The decision comes despite promising results from a Canadian study reported in the current (October 2007) issue of HIV Medicine indicating that the Biojector led to fewer injection site reactions than standard syringes.* Patients also said they preferred the Biojector and reported improved quality of life.

However, research has also shown that the Biojector may cause prolonged nerve pain and increases the risk of post-injection bleeding in certain patients. The device is also hampered by its high cost relative to standard needles and syringes.

The companies noted that the Biojector 2000 remains commercially available and that patients who wish to use the device may continue to do so.

Below is an excerpt from the Roche and Trimeris joint press release announcing the decision:

Roche and Trimeris Provide Update on Development of Alternative Administration Options for Delivery of Fuzeon

NUTLEY, N.J. and MORRISVILLE, N.C. (Oct. 3, 2007) -- Roche and Trimeris, Inc. (Nasdaq: TRMS) today provided an update on our efforts to offer a needle-free device which has been investigated for use with Fuzeon (enfuvirtide). Based on comprehensive assessment of the clinical program, as well a significant delay in achieving U.S. regulatory approval due to the time required to generate additional data, Roche and Trimeris are withdrawing a supplemental application for approval to market the Biojector 2000 device (known as "B2000" and manufactured by Bioject Medical Technologies, Inc.) for use with Fuzeon.

Importantly, Roche and Trimeris believe that patients who are currently administering Fuzeon with the device through an existing program or clinical trial may continue to do so, provided that the precautions in the current Fuzeon label regarding use with B2000 are followed. We recognize that B2000 is commercially available for general use.

"As part of our efforts to find administration alternatives, Roche and Trimeris have invested considerable resources to leverage the benefits of the B2000 device for use with Fuzeon. While the device has shown potential benefit for some patients, we don't believe it's the ideal alternative delivery option for all treatment-experienced patients. We continue to review other options for administering Fuzeon," said Michelle Zupancic, Vice President, HIV, Roche. "In addition, we continue to offer Nurse Connections, a free support program that provides patients in the U.S. with personalized, in-home instruction from a highly-trained nurse."

Facts About Fuzeon

Administered via one 90 mg injection twice-daily, Fuzeon is the first and only fusion inhibitor for the treatment of HIV. Unlike other HIV drugs that work after HIV has entered the human immune cell, Fuzeon works outside the CD4 cell, blocking HIV from entering the cell. For this reason, Fuzeon is effective in treatment-experienced patients who have developed resistance to other anti-HIV drugs, though patients may still develop resistance to Fuzeon. Fuzeon was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in March 2003 on the basis of 24-week data, and was granted traditional (full) approval on Oct. 15, 2004 on the basis of long-term 48-week data.

Fuzeon is indicated for use in combination with other antiretroviral agents for the treatment of HIV in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

Injection Site Reactions (ISRs): ISRs are the most common adverse events associated with Fuzeon. ISRs occurred in 98% of patients studied and 4% discontinued Fuzeon due to ISRs. Signs/symptoms may include pain and discomfort, hardened skin, redness, bumps, itching and swelling. Eleven percent of patients had local reactions that required analgesics or limited usual activities.

Pneumonia: An increased rate of bacterial pneumonia was observed in subjects treated with Fuzeon in the Phase III clinical trials compared to the control arm. It is unclear if the increased incidence of pneumonia is related to Fuzeon use. Patients with HIV infection should be carefully monitored for signs and symptoms of pneumonia. Risk factors for pneumonia included low initial CD4 cell count, high initial viral load, intravenous drug use, smoking, and a prior history of lung disease.

Hypersensitivity Reactions: Systemic hypersensitivity reactions have been associated with Fuzeon therapy and may recur on rechallenge. Hypersensitivity reactions have included individually and in combination: rash, fever, nausea and vomiting, chills, rigors, hypotension and elevated serum liver transaminases. Other adverse events that may be immune mediated and have been reported in subjects receiving Fuzeon include primary immune complex reaction, respiratory distress, glomerulonephritis and Guillain-Barre syndrome.

Administration with Biojector 2000: Nerve pain (neuralgia and/or parethesia) lasting up to six months associated with administration at anatomical sites where large nerves course close to the skin, bruising and hematomas have occurred with the use of the Biojector 2000 needle-free device for administration of Fuzeon. Patients receiving anticoagulants or persons with hemophilia, or other coagulation disorders, may have a higher risk of post-injection bleeding.

Other Adverse Events: The events most frequently reported in patients receiving Fuzeon plus an optimized background regimen were diarrhea (32%), nausea (23%), and fatigue (20%). These events were seen at a lower incidence in patients taking a Fuzeon-based regimen compared to those receiving an optimized background regimen without Fuzeon when taking into account the uneven number of patients in each arm and the length of time they are in that arm. As measured in number per 100 patient years, the incidence was: diarrhea (38 per 100 patient-years in subjects receiving Fuzeon-based regimens vs. 73 per 100 patient-years in patients who did not receive Fuzeon), nausea (27 vs. 50, respectively), and fatigue (24 vs. 38, respectively).

10/05/07

Sources

Roche and Trimeris, Inc. Roche and Trimeris Provide Update on Development of Alternative Administration Options for Delivery of Fuzeon. Press release. October 3, 2007.

*MR Loutfy, M Harris, JM Raboud, and others. A large prospective study assessing injection site reactions, quality of life and preference in patients using the Biojector vs standard needles for enfuvirtide administration. HIV Medicine 8 (7): 427-432. October 2007.