BMS-986094 (INX-189) Suspended HCV Study-on 'Serious' Issue

Aug 24 Updated -
BMS halts the development of BMS-986094 due to patient death
The original patient subsequently died and eight others suffered from heart and kidney toxicity, the company said in a statement released last night. Two of the patients remain hospitalized.


Safety Issue Halts Study of BMS HCV Drug
By Michael Smith, North American Correspondent, MedPage Today
Published: August 02, 2012

Bristol-Myers Squibb has suspended treatment "to protect patient safety" in a phase IIb trial of an investigational oral drug for hepatitis C.

A spokeswoman for the company said the decision was made after one of the patients getting 200 mg of the compound, dubbed BMS-986094, suffered heart failure.

Bristol-Myers Squibb is not giving further details on the patient's condition, according to Cristi Barnett, the company's associate director of public affairs.

In an email to MedPage Today, Barnett said it's still not clear what caused the heart failure or whether it's related to the study drug. To try to clarify the issue, BMS is doing "an immediate assessment of all patients receiving 094 at any dose," Barnett said.

"This assessment includes full physical exams and histories, and cardio ECHO imaging and ECGs for all patients," Barnett said. "Any clinically significant cardiac ECHO abnormality will then be reviewed by a consulting cardiologist as soon as possible."

The drug is a nucleotide NS5B polymerase inhibitor and was acquired by the company when it paid $2.5 billion in January to purchase Inhibitex, the original developer. It was first known as INX-08189.

It's one of several under development -- both Gilead Sciences of Foster City, Calif., and Vertex Pharmaceuticals of Cambridge, Mass., have competitors in the field.

The range of potential treatments for the virus, blamed for about 15,000 deaths annually in the U.S., has been expanding dramatically with the recent development of so-called direct-acting agents.

Two HCV protease inhibitors -- telaprevir (Incivek) and boceprevir (Victrelis) -- are already on the market, but they are indicated for use with pegylated interferon-alfa and ribavirin, which aim at stimulating the immune system rather than targeting the virus directly.

The goal has been to develop all-oral combinations of direct-acting agents that would eliminate the need to use interferon and ribavirin.

BMS-986094 was being tested in a two-part dose-ranging study, dubbed AI472-003, among patients with HCV genotypes 2 or 3 who had not been previously treated. Genotypes 2 and 3 are regarded as being easier to cure than genotype 1.

The first part of the 12-week study was double-blinded and included 90 patients in four treatment arms. In the comparator arm, patients were treated with pegylated interferon-alfa and ribavirin, plus an oral placebo.

In the remaining arms, patients got interferon and ribavirin plus 25, 50, or 100 mg of BMS-986094.

The second part of the study, planned to include 120 patients, was open label for 12 weeks and had five arms.

In two arms, patients took either 100 or 200 mg of BMS-986094, combined with ribavirin. In two others, they took the same doses of the drug, this time combined with daclatasvir, the company's investigational NS5A replication complex inhibitor.

Finally, in the fifth arm, they took 50 mg of BMS-986094 and both daclatasvir and ribavirin.

Michael Smith
North American Correspondent
North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers’ Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing
 http://www.medpagetoday.com/InfectiousDisease/Hepatitis/34025

Investing Commentary:
Rethinking Idenix Pharma in Wake of Bristol's Hep C Blow Up
Update Aug 6

By Nathan Sadeghi-Nejad @ The Street

NEW YORK (TheStreet) --

Last week, Bristol-Myers Squibb (BMY) confirmed my previously reported suspicions by abruptly halting a Phase II trial of BMS-094 (formerly INX-189) -- a nucleotide polymerase inhibitor, or "nuc," for the treatment of hepatitis C. One patient in the study experienced major cardiovascular toxicity, forcing Bristol-Myers to stop dosing BMS-094.....

The demise of BMS-094 has also reshaped the Hep C landscape. Let's review who still stands and where. For some assistance, I turned to John Tucker, a scientific analyst with BioMedTracker, a division of Sagient Research. Tucker recently published an excellent overview on Hep C drugs in development and he's been all over BMS-094 and its implications. At this point, combining a "nuc" with an NS5A inhibitor and the generic antiviral drug ribavirin seems to be the most promising "all oral" Hep C regimen in clinical development....

This makes Bristol-Myers' daclatasvir, an NS5A inhibitor essentially useless on its own. The company's other later-stage hep C drug candidates -- the non-nucleoside polymerase inhibitor BMS-791325 and the protease inhibitor asunaprevir -- have only modest efficacy or toxicity issues, or both. Bristol-Myers may continue to beg but I'm convinced Gilead Sciences(GILD) has no interest in a daclatasvir partnership. As I noted recently, Gilead's nuc-NS5A combination -- GS-7977 and GS-5885 -- has made rapid clinical progress and will start pivotal trials this year. In sum, the BMS-094 blowup leaves Bristol-Myers up a proverbial creek in Hep C...

I have long believed Gilead would be first to market with an all-oral Hep C regimen, but Bristol-Myers has handed the company a much bigger lead. (I also still doubt the size of the commercial market for Hep C, but that's another issue.).....

Continue Reading... Page 2

IDX-184 has a chemical structure that is similar to both BMS-094 and Pharmasset's PSI-938, another Hep C nuc that was killed off by toxicity problems last year. More specifically, the active moiety of IDX-184 -- the part of the molecule that makes the drug work -- appears to be similar to the active moieties of both BMS-094 and PSI-938. That could be a big problem.....

Page 3

Right before the Bristol-Myers news, Vertex Pharmaceuticals(VRTX) announced impressive early clinical data for ALS-2200, a nucleotide analogue licensed from Alios BioPharma. After seven days of dosing, the eight treated patients showed a median 4.54 log reduction in viral load.....

Read full article @ The Street


Bristol-Myers’ Big Bet On Hepatitis C Crashes

By Ed Silverman // August 2nd, 2012

Now, though, the Bristol-Myers bet looks questionable, at best. Last night, the drugmaker released a terse statement saying a Phase II test of the Inhibitex compound, a nucleotide polymerase that is called BMS-986094, has been suspended voluntarily due to an unspecified, but serious safety issue that is “unknown at this time.” However, analysts now say that one of 30 patients in the trial suffered heart failure in the highest daily dose of 200mg (see the listing on ClinicalTrials.gov here). 

Although the compound may not be officially dead, analysts are queasy about ballparking the Bristol-Myers strategy in hepatitis C, which was to combine BMS-986094 with its daclatasvir compound that is in Phase III testing. “While (Bristol-Myers) has other niche things going on in HCV, it is not an overstatement to say this could be a crippling setback to one of the three programs that had moved into the lead in the feverish race to usher in the interferon-free era, mid-decade, in treating hepatitis C,” wrote RW Baird analyst Tom Russo. “…We would not be surprised if it re-scrambles the space and provides another catalyst for cross-company collaborations.”

Continue reading @ Pharmalot

Bristol-Myers Suspends Hepatitis C Drug Study on 'Serious' Issue

By SAABIRA CHAUDHURI And PETER LOFTUS

Bristol-Myers Squibb Co. BMY 0.00% has suspended its study of a drug intended to treat liver disease hepatitis C after a patient suffered heart failure...  

Bristol-Myers shares—up 27% over the past year—tumbled 5.5% in premarket trading Thursday.

Late Wednesday, Bristol-Myers said it voluntarily suspended the ongoing Phase two study of BMS-986094, which was formerly known as INX-189, a nucleotide polymerase inhibitor, or "nuke." In a statement, the company said "the cause of the safety issue and any potential relationship to study drug are unknown at this time."... 

A patient who had received a 200-milligram dose of the Bristol drug experienced heart failure, said Bristol-Myers spokeswoman Sonia Choi. The company can't rule out the possibility of safety issues with patients who received other doses of the drug... 

The drug company is currently assessing all patients in the study and following an evaluation of the patient data, will decide what to do. Assessments will include full physical exams and imaging tests to measure heart health, Ms. Choi said. Any clinically significant abnormalities detected will be reviewed by a consulting cardiologist as soon as possible.

Continue Reading @ Wall Street News...

Bristol's Hep C Drug Blow Up May Benefit Gilead, Idenix, Vertex Pharma

By Adam Feuerstein

The safety issue that forced Bristol to suspend the phase II study of BMS-094 is believed to be heart failure, according to ISI Group analyst Mark Schoenebaum. Bristol is not positive that BMS-094 caused the heart failure but the company is "very concerned" and is taking the extraordinary step of evaluating all patients treated with the drug for potential heart problems, said Schoenebaum in an email to clients. 

The blow up of BMS-094 due to toxicity is not necessarily a surprise. TheStreet contributor Nathan Sadeghi-Nejad first raised safety concerns about BMS-094 in a column last May after returning from a European liver disease meeting where the drug was conspicuously absent.

"I suspect something is wrong with Bristol-Myers' INX-189, which has since been renamed by the company as BMS-094," wrote Sadeghi in the very prescient column last May. "The red flags are popping up everywhere. If I'm right about Bristol-Myers being in trouble, Gilead's lead in the race to develop all-oral therapies for hepatitis C will expand and Idenix Pharmaceuticals' hepatitis C drugs become more attractive."

Continue Reading @ The Street

Press Release - August 01, 2012 08:37 PM Eastern Daylight Time

Bristol-Myers Squibb Suspends Administration of Study Drug in Clinical Trial of Investigational NS5B Nucleotide for the Treatment of Hepatitis C

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) announced today that the Company has suspended study drug administration in an ongoing Phase II study of BMS-986094 (formerly known as INX-189), a nucleotide polymerase (NS5B) inhibitor in development for the treatment of hepatitis C. This voluntary action was taken to protect patient safety based on the emergence of a serious safety issue. The cause of the safety issue and any potential relationship to study drug are unknown at this time.

With patient safety as the priority, the Company is undertaking an immediate assessment of all patients in the study and following an evaluation of the patient data, will take appropriate actions.

About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Contacts

Bristol-Myers Squibb Company

Media:
Sonia Choi, 609-252-5132
sonia.choi@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
or
Timothy Power, 609-252-7509
timothy.power@bms.com

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