SciQuest.org

Nothing like a cute kid to make a great commercial. His interview with Ellen is priceless too.
(Hat Tip to Cynthia C. for the link)

A novel cell therapy using retinal pigment epithelial (RPE) cells attached to tiny gelatin bead microcarriers implanted in the brain can improve the symptoms of patients with moderate to advanced Parkinson’s disease (PD).

Rush University Medical Center neurosurgeon Dr. Roy A. E. Bakay and colleagues from Emory University, Atlanta found the therapy Spheramine was well-tolerated and patients experienced improvement in Parkinsonian symptoms (tremor, rigidity, slowness of movements, and impaired balance and coordination.) These findings were presented at the Annual Meeting of the American Association of Neurological Surgeons in Chicago on April 28, 2008.

The pilot study was initiated at Emory University Hospital and followed six patients with moderate to advanced PD to investigate the safety, tolerability, and efficacy of the Spheramine implantation. The full patient group has been evaluated for four years, and several have been monitored for six years. Bakay and colleagues report long-term improvement or stabilization of symptoms, maintained for a minimum of two years after Spheramine implantation. They note no Spheramine-related serious adverse events were reported and that the most frequent adverse event was postsurgical headache, which spontaneously resolved within one to two weeks.

“The results of this study are very encouraging - Spheramine is well tolerated through several years of follow-up and improvement in parkinsonian symptoms is sustained,” stated Bakay.

The cellular product Spheramine consists of RPE cells attached to microcarriers. RPE cells produce levodopa, the precursor of dopamine. Dopamine is a neurotransmitter produced by nerve cells in the brain that progressively declines as the disease progresses.

The RPE cells, which are normally found in the back of the eye, are cultured under standardized conditions and attached to the microscopic beads prior to implantation. The microcarriers are necessary for the cells to survive in the brain. The implanted cells serve as a new potential source of levodopa to enhance dopamine production where it is most needed.

The patients were selected based on disease stage, levodopa responsiveness, and severity of PD symptoms while off medication. An even distribution of Spheramine was surgically implanted into the more affected side of the brain, and patients left the hospital a few days later.

The primary efficacy measure in this trial is the motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS) when the patient has been OFF antiparkinsonian medication for at least 12 hours. The researchers report clinical improvements were noted in both UPDRS motor scores off medication (44 percent improvement from baseline at 48 months) and patient-reported quality of life scores (23 percent improvement from baseline of total PDQ-39 score at 48 months). Several of these patients have been monitored for 6 years and the trial has been extended to 10 years of follow-up.”

Bakay said positive results in the pilot study prompted the initiation of a Phase IIb, multicenter, double-blind, randomized, sham surgery-controlled study (STEPS) to further evaluate the safety, tolerability and efficacy of Spheramine. Changes from the pilot study included implantation in both sides of the brain and the addition of a sham surgery group. To date, 71 patients have been randomized for either Spheramine or sham surgery and results from the will become available later this year.

Final results of the IDEAL study, the first large, randomized, clinical study comparing the leading therapies for chronic hepatitis C, were presented at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), providing important insights that may help guide clinical practice for physicians worldwide treating this serious and potentially life-threatening disease.

The IDEAL study compared combination therapy with PEGINTRON(TM) (peginterferon alfa-2b) and REBETOL(R) (ribavirin, USP) vs. Pegasys (peginterferon alfa-2a) and Copegus (ribavirin, USP),(1) as well as a lower dose of PEGINTRON in an investigational combination with REBETOL. The results showed that sustained virologic response (SVR),(2) the primary endpoint of the study, was similar for all three treatment regimens. The study also showed in secondary analyses that PEGINTRON combination therapy provided greater predictability of response at important treatment milestones and significantly lower relapse rates after the end of treatment than Pegasys and Copegus combination therapy, despite patients in the Pegasys arm overall receiving a significantly higher median ribavirin dose over the duration of the study. Safety and tolerability were similar among the treatment arms.

“IDEAL provides important insights about the similarities and differences of the two leading combination therapies for hepatitis C, and how physicians can use these findings to help manage their patients,” said Robert J. Spiegel, M.D., chief medical officer and senior vice president, Schering-Plough Research Institute.

In IDEAL (Individualized Dosing Efficacy vs. flat dosing to assess optimaL pegylated interferon therapy), 3,070 previously untreated U.S. patients with HCV genotype 1, the most common form of the virus worldwide and most difficult to treat, were randomized and treated with one of three treatment regimens:

(1) PEGINTRON 1.5 mcg/kg/week and REBETOL 800-1,400 mg/day;

(2) PEGINTRON 1.0 mcg/kg/week and REBETOL 800-1,400 mg/day; and

(3) Pegasys 180 mcg/week and Copegus 1,000-1,200 mg/day

Patients received up to 48 weeks of combination therapy with 24 weeks of follow-up.

In IDEAL, the combination regimen of Pegasys and Copegus used the recommended doses in accordance with their approved U.S. labeling, which includes a flat dose of Pegasys (180 mcg/week) for all patients regardless of body weight, and 1,000 or 1,200 mg/day of Copegus, adjusted for two weight categories. PEGINTRON was dosed either at 1.5 mcg/kg/week or an investigational combination dose of 1.0 mcg/kg/week with REBETOL at a dose of 800-1,400 mg/day, adjusted by four weight categories.

As a result, 51 percent of patients in the study were assigned the same dose of ribavirin (either REBETOL or Copegus) based on their weight groups, 39 percent of patients in the Pegasys arm were assigned a higher dose of ribavirin and 10 percent of patients in the PEGINTRON arms were assigned a higher dose of ribavirin.

Key Findings from IDEAL

(For the PEGINTRON 1.5 mcg, PEGINTRON 1.0 mcg, and Pegasys combination arms, respectively.)

– SVR, the primary endpoint of the study, was similar for the three treatment regimens (40 vs. 38 vs. 41 percent, respectively) overall, and among those patients who were assigned equivalent doses of ribavirin based on their weight group (40 vs. 38 vs. 38 percent, respectively) (ITT).(3,4)

– Predictability of response at early treatment milestones was confirmed in a secondary analysis as an important assessment tool for physicians. More patients in the PEGINTRON combination arms who had undetectable virus (HCV-RNA) in plasma at treatment week 4 or treatment week 12 went on to achieve SVR (positive predictive value, PPV) than patients in the Pegasys combination arm (92 vs. 87 vs. 80 percent, and 81 vs. 83 vs. 74 percent, respectively).(5)

– Relapse after the end of treatment was lower for patients in the PEGINTRON combination therapy arms compared to patients receiving Pegasys and Copegus (24 vs. 20 vs. 32 percent, respectively). In a multivariate logistic regression analysis, among the factors significantly affecting relapse were: baseline viral load greater than 600,000 IU/mL vs. less than or equal to 600,000 IU/mL (p-value less than 0.001); age greater than 40 vs. less than or equal to 40 (p-value less than 0.001); fibrosis F3/4 vs. F0/1/2 (p-value equal to 0.001); Pegasys regimen vs. PEGINTRON 1.0 mcg regimen (p-value less than 0.001); glucose fasting greater than or equal to 5.6 vs. less than 5.6 (p-value equal to 0.002); steatosis 0 percent vs. greater than 0 percent (p-value equal to 0.002); ALT normal vs. elevated (p-value equal to 0.008); and Pegasys regimen vs. PEGINTRON 1.5 mcg regimen (p-value equal to 0.012).

– End of treatment response was higher in the Pegasys combination arm (53 vs. 49 vs. 64 percent, respectively).

– Ribavirin dose: One of the key questions of the study has been whether the protocol-assigned ribavirin dose regimen or the protocol-specified dose reduction schedule disadvantaged patients in any of the treatment arms, particularly in the Pegasys combination arm. However, the final results of IDEAL showed that the majority of patients in the Pegasys therapy arm received a higher ribavirin dose over the duration of the study, including patients with ribavirin dose reductions or discontinuations, based on the actual median ribavirin dose received (mg/kg/day), regardless of treatment outcome (SVR, relapsers and nonresponders) [p-value less than 0.001 for ribavirin dose received in the PEGINTRON 1.5 mcg arm vs. Pegasys arm and p-value less than or equal to 0.001 for ribavirin dose received in the PEGINTRON 1.0 arm vs. Pegasys arm].

– Safety and tolerability were similar among the three treatment groups, with no new peginterferon or ribavirin related adverse events identified in this large study. Overall adverse events reported for the three treatment regimens were similar. As seen in other studies with these treatments, a range of “flu-like symptoms” were the most commonly reported adverse events for all three treatment regimens. Overall, the proportion of patients reporting serious adverse events was similar (9 vs. 9 vs. 12 percent, respectively). Discontinuation rates due to adverse events were similar across the three treatment arms (13 vs. 10 vs. 13 percent, respectively) as were discontinuations due to psychiatric adverse events (3 vs. 2 vs. 2 percent, respectively).

The complete results of the IDEAL study will be submitted for peer-reviewed publication, as well as to health authorities worldwide.

Roche’s investigational therapy for chronic hepatitis C virus (HCV) infection, R1626, has shown a significant end-of-treatment response rate when given in combination with PEGASYS(R) (peginterferon alfa-2a) and COPEGUS(R) (ribavirin). R1626 also shows a high barrier to the development of resistance.

After four weeks of treatment with this triple combination, followed by 44 weeks of PEGASYS and COPEGUS, levels of HCV were undetectable in 84 percent of patients infected with genotype 1 virus. This was higher than patients treated with PEGASYS and COPEGUS alone for the entire 48-week treatment period (65 percent). These new data were presented in a late-breaker oral session at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), being held in Milan, Italy.

R1626 was discovered and developed at Roche and belongs to a class of antivirals called polymerase inhibitors, which are being investigated with the current standard of care for hepatitis C combination therapy with pegylated interferon and ribavirin.

“These results demonstrate that R1626 holds significant promise to potentially increase the number of hepatitis C patients who can be successfully treated,” said Dr. David Nelson, Director of Hepatology and Liver Transplantation at the University of Florida, Gainesville, Florida. “Since most patients responded very early in treatment with R1626, we expect sustained virological response (SVR) rates that improve significantly on those achieved with the current standard of care. I look forward to SVR data from this Phase IIa study, and to results of the ongoing Phase IIb study.”

Patients in this Phase IIa study will be followed for an additional 24 weeks with no treatment to determine the SVR rate, which indicates successful treatment