AmiKet™

Indication

Relief of pain associated with neuralgia due to chemotherapy (CIPN), shingles in adults (PHN) or diabetes (DPN)

Target Population

15 million patients

Description

4% amitriptyline and 2% ketamine cream

Dosage and Administration

4 mL topical cream twice daily

Adverse Reactions

Mild sensitivity at application site

Experience

Over 1,700 patients treated in seven clinical trials

Description

AmiKet™ is a prescription topical analgesic cream designed to provide effective, long-term relief from the pain of peripheral neuropathies. Peripheral neuropathies are medical conditions caused by damage to the nerves in the peripheral nervous system. The peripheral nervous system includes nerves that run from the brain and spinal cord to the rest of the body. It is estimated that these conditions affect more than 15 million people in the U.S. These conditions are caused from injured peripheral nerves, caused by herpes zoster, or shingles, diabetes, chemotherapy, HIV and other diseases. Peripheral neuropathies can also be caused by trauma or may result from surgical procedures. AmiKet™ cream is a patented formulation containing two FDA-approved drugs, amitriptyline (a widely-used antidepressant) and ketamine (an NMDA antagonist that is used as an anesthetic).

In February 2011, data was presented from the Phase IIb trial for AmiKet™ in CIPN, which was conducted by the National Cancer Institute (NCI) under the direction of the NCI funded Community Clinical Oncology Program (CCOP).  More than 460 cancer survivors suffering from painful CIPN were enrolled in the six-week study. The results of the trial in the intent to treat, or ITT, population demonstrated that the change in average daily neuropathy intensity scores in the AmiKet™ group achieved a statistically significant reduction in CIPN intensity versus placebo (p<0.001), which was the trial's primary endpoint. Additionally, a pre-specified subgroup of the ITT population, those patients who previously received taxane chemotherapy, also showed a statistically significant reduction in average daily neuropathy intensity scores (p=0.034). This subgroup constituted more than 50% of the ITT population. Secondary efficacy endpoints confirmed the superiority of AmiKet^TM vs. placebo. Furthermore, the safety profile of AmiKet^TM was comparable to placebo.

In January 2009, the results of a four-week, Phase IIb, 360 patient trial in post-herpetic neuralgia (PHN) were reported. The trial compared the efficacy and safety of AmiKet™ against both gabapentin and placebo. The data demonstrated that AmiKet™ achieved statistically significant superior efficacy compared with placebo (p=0.024). An additional primary endpoint, to demonstrate that AmiKet™ was not inferior to gabapentin in reducing pain, was also met. A key secondary endpoint measured in the trial from a responder analysis indicated that 63% of patients in the AmiKet™ treatment arm achieved a reduction in pain scores of at least 30%, significantly higher than that of patients in the placebo arm (p=0.033). Data results further indicate that AmiKet™ achieved a superior safety profile when compared with gabapentin, especially with regard to dizziness and somnolence, as evaluated by the reporting of adverse events.

In February 2008, the results of a four-week, Phase IIb trial in diabetic peripheral neuropathy (DPN) were reported (Neuracept). The Neuracept trial was a double blind, placebo-controlled study of AmiKet™ in 215 DPN patients who completed the trial. The data demonstrated that the primary endpoint, the difference in changes in pain intensity between AmiKet™ and placebo over the four week duration of the trial, nearly reached statistical significance (p=0.0715). Key secondary endpoints measured in the trial indicate that 60% of patients in the AmiKet™ treatment arm achieved a reduction of pain scores of at least 30% compared with 48% of patients in the placebo arm (p=0.076). In addition, 33% of patients in the AmiKet™ treatment arm achieved a reduction in pain scores of at least 50% compared with 21% of patients in the placebo arm (p=0.078). All pain scores measured trended in favor of the AmiKet™ treated patients over the placebo group, indicative of an analgesic effect. 

Stage of Development

The key element of a proposed Phase III clinical program is a 12-week, four-arm, factorial-designed trial in CIPN that would seek to demonstrate AmiKet’s superiority compared with placebo and with each of the component drugs of AmiKet™, amitriptyline and ketamine. The protocol for this trial will be submitted to the FDA via a Special Protocol Assessment (SPA). An additional two-arm efficacy study in another painful peripheral neuropathy may be performed as an alternative strategy to a second factorial-designed trial for the NDA filing, which could potentially lead to a broader label in the treatment of peripheral neuropathic pain.

EpiCept intends to partner AmiKet™ prior to the commencement of the Phase III program in order to share the costs and development risk, and ultimately to have that partner market the product globally upon approval.  Partner discussions are continuing.