|Repligen's promising potential in 2011|
|By Patrick Crutcher|
|Thursday, 23 December 2010 09:13|
Repligen Corporation (NASDAQ: RGEN) is another attractive biotech that has revenues, cash and pending data in early 2011. With pending Phase 2 and Phase 3 data, Repligen seems set for a transformative 2011.Specifically, they have 2 important clinical catalysts in Q1 2011: Phase 3 data for RG1068 (pancreatic imaging agent) and Phase 2b data for their bipolar drug (RG2417). Both of these catalysts have the potential to take RGEN to new levels in 2011.
Phase 2a results demonstrated a statistically significant reduction in the symptoms of depression in patients receiving RG2417 (vs. placebo) on the MADRS and on the CGI-BP-C scale over the 6-week course of the study. RG2417 was safe and well tolerated. Repligen has exclusively licensed this patent from McLean Hospital, the largest psychiatric facility of Harvard Medical School. RGEN intends on seeking a partner, since this drug has a potential $2 billion market. Positive results from this trial could result in significant appreciation of their value. Enrollment is complete in this trial and most clinical work should be done by the end of the year. Results are expected in early Q1 2011.
In our view, the data were largely positive and with a new, more robust protocol and CRO, the study should achieve it’s primary endpoint. Pooled data from all three radiologists resulted in a statistically significant improvement in sensitivity with RG1068 (p=0.005) with minimal loss in specificity. With the RG1068-enhanced MRI images, RGEN saw highly statistically significant(p<0.001) improvements on other endpoints like improvements in image quality, ability to see all three segments of the pancreatic duct, and physician confidence in their ability to identify pancreatic duct abnormalities, when compared to MRI alone. There were no serious adverse events (SAEs) associated with the RG1068-MRI procedures compared to 55 SAEs associated with ERCP. Clearly, RG1068 offers advantages over ERCP, in terms of economics and patient care. RGEN has modeled the market for RG1068 at over $100 million.
Recently, Repligen received $1.4 million in research funding from the Muscular Dystrophy Association to support the ongoing development of RG3039 for Spinal Muscular Atrophy(SMA). RG3039, our lead compound, is an inhibitor of an RNA processing enzyme which targets increased production of SMN, a protein of deficient levels in patients with SMA. Repligen hopes to complete preclinical studies and advance RG3039 into human clinical testing in 2011. Additionally, they received orphan drug designation from the FDA for RG2833, a selective histone deacetylase 3(HDAC-3) inhibitor for the treatment of Friedreich’s ataxia. They hope to move this into Phase 1 next year.
Repligen is the world’s biggest supplier of recombinant Protein A, necessary for the production of monoclonal antibodies. This year, Repligen entered into a 5-year supply agreement with GE Healthcare Bio-Sciences AB for recombinant Protein A. They have had steady a steady source of income from this and they are project $22-24M in revenue for fiscal year 2011. Repligen has $50+ million in cash and significant insider/institutional ownership with about 30 million outstanding. We also feel strongly about management's ability to deliver positive results.
To help us better understand RG2417 for bipolar disorder, we contacted Repligen’s CEO and President, Walter C. Herlihy, with some questions regarding RG2417.
BioMedReports: Can you get me some information about the study design for the Phase 2b clinical trial of RG2417? Discussion about the power of trial would be helpful and the primary endpoint.
Herlihy: The RG2417 Phase 2b study in patients with bipolar disorder is a double-blind, placebo-controlled trial designed to assess the efficacy of 8 weeks of treatment with RG2417 or a placebo on the symptoms of bipolar depression as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). This study has enrolled 175 patients at 29 clinical sites within the United States, and we expect to report top-line results in the first quarter of 2011.
Essentially the study was powered using the data from the Phase 2a study. A difference in MADRS of 3 points with a standard deviation of 10 would be 80% powered with 55 completers in each treatment arm. With a 33% early termination rate, we will be powered after recruiting 165 patients.
The primary objective of this study is to assess the safety and efficacy of RG2417 on the symptoms of bipolar depression by demonstrating a greater improvement in the MADRS score of the patients receiving RG2417 when compared to placebo using a repeat measures statistic over the 8-week treatment period.
Patients are initially screened for a score of bipolar depression symptoms of greater than 20 on the MADRS and subsequently confirmed to meet the criteria for bipolar depression using an alternate diagnostic tool to ensure that patients have the appropriate diagnosis for inclusion in the study. Evaluations for symptoms of depression are conducted at baseline and then weekly using the MADRS, a standardized, rater-administered scale, which has been used for numerous drug trials in bipolar disorder. In addition to the MADRS ratings, patients conduct a weekly self-assessment of their symptoms, which is used to cross check the fidelity of the MADRS raters.
Additional secondary and exploratory objectives include improvements in the Clinical Global Impression Scale, difference in the end of study MADRS scores, and a lack of increase in mania as measured by the Young’s Mania Rating Scale. The average baseline MADRS of the 175 patients recruited into this study was 31.3 compared to 30.4 in the Phase 2a study and there has been a high degree of fidelity between the MADRS scores determined by the raters and the patient’s self-assessment of depression symptoms during the 8-week treatment period. To date, there have been no serious adverse events determined to be related to RG2417, which continues to support an advantageous tolerability and safety profile for the drug.
BioMedReports: Can you discuss the results from the Phase 2a study of RG2417?
RGEN completes RG2417 enrollment in Phase 2b study - http://bit.ly/a5htB8
FDA and EMA Approval of Re-analysis of Images from Phase 3 Trial of RG1068 for Pancreatic Imaging - http://bit.ly/h8ZPty
RGEN Phase 3 results of RG1068 in Pancreatic Imaging - http://bit.ly/h31k7s
2010 Annual Report (1.3MB PDF) - http://bit.ly/fP26fo
RGEN October 2010 Presentation - http://slidesha.re/gzs4iI