Tedizolid Phosphate (TR-701) Profile
Tedizolid phosphate (TR-701), formerly torezolid phosphate, is a second generation oxazolidinone being developed for the treatment of serious gram-positive infections, including those caused by MRSA. Tedizolid phosphate is the second generation oxazolidinone furthest advanced in clinical development for the treatment of such infections. Tedizolid phosphate is a novel prodrug antibiotic that is cleaved in the blood stream to the active compound, tedizolid (TR-700).
As a second generation oxazolidinone, tedizolid phosphate shares the positive attributes of linezolid, including the availability of IV and oral dosage forms, highly efficient oral absorption and tissue penetration and distribution, and activity against MRSA. However, based on clinical and nonclinical data, we believe that tedizolid phosphate has significant potential advantages over linezolid, including the following:
- Greater Potency.
The potency of tedizolid is four to eight times greater than linezolid against linezolid-susceptible strains and up to 16 times greater than linezolid against linezolid-resistant strains. The greater potency of tedizolid phosphate should enable a shorter course of treatment as compared to linezolid. We believe that this enhanced potency may result in improved clinical outcomes, significant savings for hospitals and payor organizations, faster eradication of the pathogen and earlier discharge from the hospital.
- Shorter Dosing Regimen and More Convenient, Once Daily Dosing.
Tedizolid Phosphate is administered once daily for six days for the treatment of cSSSI (now termed ABSSSI), as compared to twice daily for 10 to 14 days for linezolid. We believe this shorter and once daily dosing regimen will contribute to improved patient compliance, decrease the risk of drug induced adverse events and limit the emergence of resistance.
- Bactericidal Activity In Vivo.
Tedizolid Phosphate (TR-701), unlike linezolid, concentrates to a high extent inside certain white blood cells, which engulf pathogenic bacteria and concentrate at the site of infection. This feature of Tedizolid phosphate (TR-701) contributes to its in vivo bactericidal activity, or killing of pathogenic bacteria in the body, which is thought to yield a higher degree of efficacy and faster eradication of the pathogenic bacteria than is achieved with bacteriostatic antibiotics, which are antibiotics that arrest the growth of bacteria.
- Activity Against Key Gram-Positive Drug-Resistant Strains
and Select Atypical
and Gram-Negative Bacteria.
Tedizolid phosphate is active against all clinically relevant gram-positive bacteria tested to date, including organisms resistant to linezolid and other antibiotics. Tedizolid phosphate is also active against strains of the gram-negative bacterium Legionella and strains of the atypical bacterium Chlamydia, and thus may have utility in treating lower respiratory tract infections involving these bacteria.
- Low Intrinsic Frequency of Resistance.
The frequency at which MRSA evolves resistance to Tedizolid phosphate is 16 times lower than the frequency at which it evolves resistance against linezolid. We believe that this may enable wider use of Tedizolid phosphate and limit the emergence of resistance.
- Favorable and Predictable Pharmacokinetics
There is little patient-to-patient variability in the concentration of tedizolid phosphate in blood, as compared to linezolid. As a result, we expect that tedizolid phosphate will have more predictable drug exposure which may lead to a more uniform efficacy and safety profile across different patients when compared to linezolid.
- Fewer Drug-Drug Interactions.
Unlike linezolid, tedizolid phosphate has not been shown to inhibit the monoamine oxidase system which mediates the metabolism of tyramine, SSRI's and vasoconstrictors.
- Improved Safety Profile for Longer Term Dosing.
The results of our comparative 21-day Phase 1 clinical trial show that a 200 mg daily dose of tedizolid phosphate had less impact on hematological parameters indicative of myelosuppression than the labeled dose of Zyvox (600 mg twice daily). Based upon the results of this clinical trial, we believe that Tedizolid phosphate may offer a safer alternative to linezolid for infections requiring longer term dosing, such as bacteremia.
In summary, we believe that tedizolid phosphate may provide physicians with a safe antibiotic for the treatment of serious gram-positive infections that is more potent and more convenient than linezolid and other currently available alternatives. Further, we believe use of tedizolid phosphate will result in earlier discharge from the hospital, lower incidence of resistance and reduced need to switch to alternative antibiotics. All of these factors may contribute to reduced cost for treating serious gram-positive infections.