I never got the chance to flesh out this blog post to the extent planned, but I thought I would publish it nonetheless to capture the archive of links, statements, etc regarding the controversy around the disclosure of the safety and efficacy data for "FLINT" study evaluating obeticholic acid (OCA) from Intercept Pharma $ICPT in nonalcoholic steatohepatitis (NASH).
Those of us who raised an eyebrow about the initial disclosure from ICPT have been correct in that there was more to the story. Thankfully much more of the full picture is now in the public domain and the path forward will lie in the hands of the upcoming data from the clinical trial. The assessment of management's behavior and the impact on credibility going forward is up to each investor.
Those of us who raised an eyebrow about the initial disclosure from ICPT have been correct in that there was more to the story. Thankfully much more of the full picture is now in the public domain and the path forward will lie in the hands of the upcoming data from the clinical trial. The assessment of management's behavior and the impact on credibility going forward is up to each investor.
November 19, 2013 - January 31, 2014
Date range of disclosed emails among ICPT management and NIH/NIDDK clinicians who conducted the FLINT study (see link below)
January 8, 2014
$ICPT closing price $72.35
January 9, 2014
"Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept) today announced that the FLINT trial of obeticholic acid (OCA) for the treatment of nonalcoholic steatohepatitis (NASH) has been stopped early for efficacy based on a planned interim analysis showing that the primary endpoint of the trial has been met...The decision to stop FLINT has been based on the recommendation of the Data Safety Monitoring Board (DSMB) which reviewed liver biopsy data from before and at the end of the treatment period in approximately half of the 283 randomized patients, in accordance with a planned interim efficacy analysis. This analysis demonstrated that OCA treatment resulted in a highly statistically significant improvement (p=0.0024 on an intention-to-treat [ITT] basis) in the primary histological endpoint, defined as a decrease in the NAFLD Activity Score (NAS) of at least two points with no worsening of fibrosis, as compared to placebo. Those patients who had not yet completed the trial and therefore did not have a second biopsy were treated as non-responders in the ITT analysis. The pre-defined threshold of statistical significance for stopping FLINT was p < 0.0031."
At the time, one might have wondered why both arms of the trial were not permitted to carry forward and receive such a wonder drug...
$ICPT closing price $275.87
January 10, 2014
Amarin AMRN cancels its JP Morgan Healthcare Conference presentation and ICPT gets its slot.
$ICPT closing price $445.83
NIDDK issues its own comments after hours, initially to the WSJ, disclosing the safety findings for the first time. There was not a public press release but the statement was eventually released by the company (see 8-K link below)
January 12, 2014
ICPT issues a new press release acknowledging the NIDDK statement and making the following comments: "The NIDDK confirmed...Its decision to halt the 72-week therapeutic phase of FLINT was based on interim efficacy results showing that "OCA has a significant beneficial effect on liver damage due to NASH"...Lipid abnormalities involving increased total cholesterol and LDL and decreased HDL were seen in OCA-treated patients compared to placebo...Since lipid abnormalities are common in NASH, all of the patients will be followed for the 24-week period to help determine whether lipids return to pre-treatment levels...While the NIDDK did not provide any information concerning the magnitude of lipid effects, Intercept believes that the reported lipid changes in FLINT patients on OCA will likely be similar to the results previously reported in a clinical trial of OCA"
March 14, 2014
ICPT files their annual report on form 10-K to the SEC.
"The NIDDK’s decision to stop the treatment phase of FLINT in January 2014 was based on the recommendation of the trial’s Data Safety Monitoring Board, or DSMB, which reviewed liver biopsy data from before and at the end of the treatment period in 164 (58%) of the 283 randomized patients, in accordance with a planned interim efficacy analysis. This interim analysis demonstrated that OCA treatment resulted in a highly statistically significant improvement (p=0.0024 on an intention-to-treat, or ITT, basis) in the primary histological endpoint, defined as a decrease in the NAS of at least two points with no worsening of fibrosis as compared to placebo, which met the pre-defined threshold of p<0.0031 for stopping the treatment phase of FLINT. As specified in the FLINT protocol, the NIDDK’s decision to stop the treatment phase early was based primarily on OCA therapy having met the pre-defined efficacy criterion, while being informed by the risks involved in conducting liver biopsies in the remaining patients and the available safety data described below. All patients have stopped dosing of OCA and placebo and have entered into a pre-specified 24-week observational follow-up phase, during which blinding is maintained...The NIDDK previously noted that disproportionate lipid abnormalities consisting of increases in total cholesterol, together with increases in LDL cholesterol and decreases in HDL cholesterol, have been observed in the patients taking OCA in the trial. Although we do not yet know the magnitude of these lipid effects or whether OCA treatment also resulted in a concomitant decrease in triglycerides, we believe that the observed lipid changes appear to be consistent with the pattern observed in the diabetic NAFLD patients treated with OCA in our previous Phase 2 trial...We recently received a report of blinded FLINT safety data from the NIDDK and have learned that as of the end of December 2013 a total of ten cardiovascular serious adverse events had occurred in seven (2.5%) of the patients in FLINT across both treatment groups, at which point 207 (73%) patients had completed the 72-week treatment phase and 73 remaining patients had all been on study for 60 weeks or more. As part of its review, the trial’s DSMB expressed concern regarding hyperlipidemia and the occurrence of serious cardiovascular events, both of which were seen in both the treatment and placebo groups, but disproportionately in patients receiving OCA. However, the NIDDK has advised us that while the incidence of the serious cardiovascular events was numerically higher in the patients receiving OCA therapy, it was not statistically significantly different as compared to the placebo group..In January 2014, the NIDDK stopped the double-blind treatment phase of the FLINT trial early following a planned interim analysis showing that OCA had met the primary efficacy endpoint of the trial based on a pre-defined interim efficacy criteria. However, the NIDDK has not yet provided us with the dataset upon which the data safety monitoring board, or DSMB, based its recommendation to halt the FLINT trial. This dataset may include additional details regarding OCA that may not be expected or desirable, such as the magnitude of the efficacy and the overall adverse event profile of patients on OCA treatment...We have been engaged in an ongoing dialogue with the NIDDK with the goal of obtaining additional data from FLINT. As part of its review the trial’s DSMB expressed concern regarding hyperlipidemia and the occurrence of serious cardiovascular events, both of which were seen in both the treatment and placebo groups, but disproportionately in patients receiving OCA...Because this trial is still blinded, we do not have further information regarding the adverse event profile of the other patients in the trial, which could include side effects that are unexpected or undesirable. We anticipate that the full safety information relating to OCA from the FLINT trial in NASH will be provided to us together with the final results. "
April 4, 2014
ICPT files prospectus and sells 1 million shares at $320 per share. The safety disclosure appears to match that published in the annual report.
May 20, 2014
Adam Feuerstein (The Street) publishes an article highlighting the email exchange between ICPT and NIDDK, as originally detailed in a Favus report.
ICPT stock closes at $223.34, down from $280.26 on May 16 before the emails surfaced.
May 22, 2014
Intercept Pharma files an 8-K with the SEC containing the full collection of emails that had been released via a FIOA request. The emails provide the details of how the company worked to publicizing the efficacy findings that led to the stopping of the trial while also working to blunt / minimize the disclosure of the safety findings.
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