Sovaprevir (Formerly ACH-1625) is a experimental protease inhibitor developed
by Achillion Pharmaceuticals to treat hepatitis C
June 10 2014
FDA lifts clinical hold on Achillion's HCV drug sovaprevir, shares jump
Achillion Pharmaceuticals' shares surged as much as 62 percent Tuesday after announcing that the FDA removed a clinical hold on its NS3/4A protease inhibitor sovaprevir and that it can resume testing the experimental drug as a potential treatment for hepatitis C viral (HCV) infection. Chief medical officer David Apelian remarked that the drugmaker is "very pleased that the effort by the Achillion team, working in collaboration with the FDA, has resulted in this response for the sovaprevir programme."
Sept 27 2013
Achillion Pipeline Update:Hepatitis C Drug Still on Hold by U.S. FDA
Achillion today received a response from the U. S. Food and Drug Administration, or FDA, on the clinical hold related to sovaprevir, Achillion's NS3 protease inhibitor. The FDA response indicated that, while Achillion's submission addressed all issues noted in the FDA's June 29, 2013 letter, the FDA concluded that the removal of the clinical hold is not warranted.
July 2 2013
Achillion Hepatitis C Drug Trial on Hold on Liver Concern
Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that the Company has received notice from the
U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on sovaprevir after elevations in
liver enzymes associated with significantly higher than anticipated exposures to atazanivir and sovaprevir
were noted in a Phase 1 healthy subject drug-drug interaction (DDI) study evaluating the effects of concomitant
administration of sovaprevir with ritonavir-boosted atazanavir. The FDA has allowed continued enrollment and
treatment of patients in the Phase 2 -007 clinical trial evaluating 12-weeks of sovaprevir in combination with ACH-3102 and ribavirin for patients with treatment-naive genotype 1 hepatitis C viral infection (HCV).......
How Bad Will The Partial Hold On Sovaprevir Be For Achillion?
Seeking Alpha - Stephen Simpson
Achillion (ACHN) investors got a huge piece of bad news on
Monday evening, when this biotech virology specialist announced that its lead
protease inhibitor for hepatitis C (HCV), sovaprevir, has been placed on
clinical hold by the FDA after troubling safety data. With the stock down
sharply in after-hours trading, this is clearly a major near-term problem for
the company and the stock, and it definitely raises troubling questions about
the safety profile of this drug.
While I do not believe this development devastates the long-term potential of
the drug in HCV treatment, it most likely freezes any possibility of an
acquisition and it is almost certainly going to appear as an issue if/when the
company files for FDA approval.
An Unexpected Safety Problem In Healthy Patients
This partial clinical hold on sovaprevir did not come from the company's
ongoing studies of sovaprevir in HCV patients. Rather, the safety issue
appeared in a small (31-patient) study of healthy test subjects receiving
sovaprevir with ritonavir-boosted atazanavir. The purpose of this study was to
test for potential drug interactions, and that seems to be exactly what has
In 16% (5 of 31) of the patients, worrisome elevations of ALT liver enzymes
were detected, which indicates damage to the liver. Two of the patients had
grade IV elevations and three had grade III elevations, though none of them
reached the technical definition of a serious adverse event.
Why Do This Study?
Ritonavir-boosted atazanavir is a relatively common treatment option for
people with HIV, and atazanavir is a member of the protease inhibitor class.
Although atazanavir is generally safe in HIV patients co-infected with HCV,
prior studies have seen single-digit percentages discontinue the drug due to
So why would Achillion even do a combination study like this?
Approximately 25% of HIV patients in the U.S. are co-infected with HCV, and
so it stands to reason that the FDA will want information on the safety and
efficacy of these new HCV drugs in HIV patients taking some of the most
commonly-prescribed medications. Along those lines, Achillion has done many
other drug interaction studies with sovaprevir (with oral contraceptives, for
instance), and thus far the drug had been building an attractive drug
What's The Impact?
I think it's very important to note that the FDA has NOT ordered a halt or
hold on the company's ongoing study of sovaprevir in the Phase 2 "007" study in
combination with ACH-3102. I think it's also important to note that similar
liver enzyme elevations have not been seen in prior HCV studies, nor in prior
drug interaction studies.
I wouldn't say that Achillion was completely clear in its conference call,
but it sounds like there was an unexpected synergistic effect between
sovaprevir and atazanavir, leading to much higher effective doses (plasma
concentrations). Nevertheless, this brings investors very much back to mind of
the clinical hold and troubling safety data that ruined the HCV drug
Bristol-Myers (NYSE: BMY) acquired from Inhibitex and the clinical hold
currently on an Idenix (IDIX) HCV drug. While it's worth noting that
sovaprevir is a different drug and those other two drugs showed troubling
safety data in HCV studies, the reality is that "elevated liver enzymes" is
never good news when you're talking about a drug that treats a liver
If the safety data on sovaprevir remains otherwise intact and the FDA permits
ongoing studies of the drug, the impact of this development may ultimately be
modest. Though 25% of HIV patients are co-infected with HCV that amounts to
about 275,000 patients in the U.S., or about 7% of estimated HCV patients.
Likewise, not all of those patients are on atazanavir, so the ultimate market
share/financial impact to Achillion could be modest.
But those are significant "ifs." Who's to say what will happen in further
drug interaction studies, or in long-term use of sovaprevir in HCV patients.
Moreover, with the multi-billion dollar soaking that Bristol-Myers took on
Inhibitex, it is not unreasonable to think that this development has chilled
any considerations of a pharma company or larger biotech acquiring Achillion.
Likewise, with Gilead (GILD) and AbbVie (ABBV) potentially as much as two years
ahead of Achillion and holding excellent safety and efficacy data, any drawback or
issue with sovaprevir is significant today.
What Should Investors Do Now?
Given that it was only a week ago that I wrote up Achillion as a potential
double in the biotech space, I feel terrible about this development. Along the
same lines, I don't want to be seen as "talking down" this bad news in an
effort to preserve face or ego. In the results-only world of Wall Street, this
is an absolutely miserable call so far, and I have no intention of hiding from
Still, I don't think this is the end. Management indicated on the call that
they had not seen even grade I ALT elevations in prior studies of sovaprevir,
so I really do think this just happened to be a bad luck mix of two drugs that
really don't work well together. In market terms, it certainly sullies the
commercial profile of sovaprevir, but I never expected sovaprevir to be the
lead drug in the HCV space, and I don't believe the "HIV co-infected with HCV
and taking atazanivir" market segment is large enough to fundamentally alter
If I held Achillion shares going into this reversal, I'd likely continue to
hold. The damage has been done, and I think there's still a case to make that
the drug can be a safe, effective, and appealing treatment option for
non-HIV-infected HCV patients (the other 93%). If I take 7% out of my prior
revenue estimate and up the discount rate by more than 15% to account for the
added risk, the new suggested fair value is a still-appealing $12.25.
All told, I simply don't know what to make of this new information. Any
negative information on safety for an HCV drug is very serious, and I don't
want to diminish that, but I think there is a substantial difference between
negative safety data from an actual HCV study and data from a drug interaction
study that may only apply to a small percentage of the target market. Though
Achillion is now a much riskier call, I do believe it still has a fighting
chance to be a factor in the new generation of HCV therapies.
EASL: Achillion Presents New Data on ACH-3102 to Treat Hepatitis C
April 16 2013
Achillion Initiates Phase 2 Interferon-Free Trial of Sovaprevir and ACH-3102 for Genotype 1 HCV
Jan 14 2013
Achillion Continues To Make Significant Strides In The Fight Against Hepatitis C
On Monday January 7th, it was announced that Achillion's
ACH-3102 (a drug candidate currently being developed to treat chronic hepatitis
C viral infections), in combination with antiviral drug ribavirin, had shown
positive progress during a Phase 2a study of 8 patients. According to the
company's President of Research and Development and
Chief Scientific Officer, Milind Deshpande, Ph.D, "As the first-ever
clinical trial to evaluate an NS5A inhibitor as a single direct-acting
antiviral in combination with ribavirin, we are extremely encouraged by these
initial results that demonstrate rapid suppression of the HCV GT1b virus and a
well-tolerated safety profile through 12 weeks of therapy". If the company can
continue to make significant strides against the spread and life expectancy of
the HCV GT1b virus, investors may want to consider this as a positive catalyst
and look to increase their position when future developments are announced....
Jan 7 2013
Sovaprevir (ACH-1625; Achillion Pharmaceuticals, New Haven, CT) is another NS3 protease inhibitor with very high potency, reporting a half-maximal inhibitory concentration of ~1 nm. A phase IIa studyreported that ACH-1625, with PEG-IFN/RBV, resulted in a RVR in 75–81% of subjects compared with a RVR of 20% in patients receiving PEG-IFN/RBV alone . A phase IIb study is under way at this time, but given the true second-generation PI also from Achillion (see below), it is less likely that this PI will be carried through to phase III trials.
ACH-2684 (Achillion Pharmaceuticals) is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and a safety profile at
high drug exposures that strongly supports once-a-day dosing. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. It has preclinical activity against the six known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 pm .
Achillion Pharmaceuticals, Inc reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients
with HCV genotype 1 treated with ACH-2684 achieved a mean maximum 3.73 log10 reduction in HCV RNA after 3-day 400-mg monotherapy with once-a-day dosing. The compound also demonstrated good safety and tolerance both in healthy volunteers and in patients with HCV. This PI seems to represent an ideal partner for all-oral regimens that can help deliver
pangenotypic activity with a high barrier to resistance...read more...
Jan 3 2012
Achillion: Poised For Growth And Now Is The Time To Buy
What is notable is that Achillion has 4 drugs in the mix; ACH-2684, 2928, 3102 and 1625.
Each of which are showing strong promise at various phase I and II trials, and can either work independently or in combination in an oral fashion, not injections.
Achillion Provides Update on Clinical HCV Development Programs
AASLD-Achillion Programs: Sovaprevir, ACH-3102 and ACH-2684
Achillion hepatitis C drug shows promise in mid-stage study
Aug 7 2012
Reuters) - Achillion Pharmaceuticals Inc said its experimental hepatitis C drug
showed promising interim data in a mid-stage trial, sending its shares higher in
The company said the drug sovaprevir, when given along with the standard therapy of
pegylated interferon and ribavirin, showed no detectable virus level in a
majority of patients four weeks after the end of the treatment period.
Of the 39 patients who received 12 weeks of additional standard therapy following 12 weeks
of the combination therapy, a total of 33 patients in three different dosage arms showed sustained
viral response a month later.
Trial results from the same patients at 12 weeks post treatment, as well as from
another arm where 14 patients received 36 weeks of standard treatment following
combination therapy, are expected in the first quarter of 2013.
Additionally, the company said it has begun early studies to evaluate the safety of another
one of its experimental hepatitis C drugs, codenamed ACH-3102, and expects to
report initial results from this in the third quarter.
"The safety and tolerability seen to date with ACH-3102 ... lead us to believe we
have an in-house portfolio of optimized compounds that can successfully create
an all-oral, interferon-free regimen for the treatment of genotype 1 HCV,"
Achillion's chief scientific officer Milind Deshpande said in a statement.
Hepatitis C drugmakers have been scouting for ways to develop an effective drug t
hat does not contain interferon, which causes flu-like symptoms that often lead patients to
Companies such as Vertex Pharmaceuticals Inc, Bristol Myers-Squibb and
Abbott Pharmaceuticals are currently in the race to get such a treatment to market.
(Reporting by Zeba Siddiqui in Bangalore; Editing by Anthony Kurian)
Achillion Announces Positive SVR4 Results From Phase 2 Study of
Sovaprevir (Formerly ACH-1625) and Advancement of ACH-3102
Sovaprevir (formerly ACH-1625)
achieves SVR4 of 85-100% of genotype 1 treatment naive patients treated with
sovaprevir for 12 weeks followed by an additional 12 weeks of
pegylated-interferon and ribavirin
Enrollment of HCV-infected patients initiated in Phase 1 trial of ACH-3102, second generation
pan-genotypic NS5A inhibitor
Conference call tomorrow August 8, 2012 at 10:00 a.m. EDT
NEW HAVEN, Conn., Aug. 7, 2012 (GLOBE NEWSWIRE) -- Achillion
Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced sustained viral response
(SVR4) results of 85 to 100 percent from an ongoing multi-dose Phase 2 trial
evaluating 12 weeks of dosing with sovaprevir (formerly ACH-1625), a once-daily
protease inhibitor, in combination with pegylated interferon plus ribavirin
(P/R) followed by an additional 12 weeks of P/R. In addition, the Company
announced today that ACH-3102, a second-generation pan-genotypic NS5A inhibitor,
has been safe and well tolerated by healthy volunteers in both single and 14-day
multiple ascending dose groups. Further, enrollment of patients in a Phase 1
proof-of-concept clinical trial to evaluate the safety and efficacy of ACH-3102
in patients with genotype 1 HCV has been initiated.
"We are very pleased to reach these important milestones in our HCV portfolio including
positive SVR4 results with sovaprevir and the advancement of ACH-3102, our second-generation
pan-genotypic NS5A inhibitor, through Phase 1 dose-escalation," commented Milind
S. Deshpande, Ph.D., President of Research and Development and Chief Scientific
Officer. "The safety and efficacy seen with sovaprevir across dose groups
provides us with confidence that this next-generation protease inhibitor will
play an important role in an all-oral treatment for HCV. The safety and
tolerability seen to date with ACH-3102, for which we expect to report
proof-of-concept next month, combined with the compound's in vitro profile, lead
us to we believe we have an in-house portfolio of optimized compounds that can
successfully create an all-oral, interferon-free regimen for the treatment of
genotype 1 HCV. We look forward to beginning combination studies with sovaprevir
and ACH-3102 by the end of the year."
Sovaprevir: Updated Phase 2 results including SVR4
In June 2011, Achillion initiated a randomized Phase 2
trial evaluating three doses (200 mg, 400 mg, or 800 mg) of sovaprevir given
once daily in combination with pegylated interferon plus ribavirin (P/R) for 12
weeks followed by an additional 12 or 36 weeks of P/R, for the treatment of
genotype 1 HCV.
As previously reported in April 2012, of the 58 patients
enrolled in this study, the majority had HCV genotype 1a (n=35 (60%)), with
remaining patients having HCV genotype 1b (n=20) or genotype 1 (n=3).
Approximately 71% of the patients were IL28B genotype CT/TT, the more difficult
to treat mutation, 64% were male and 17% were African American. The complete
early virologic responses (cEVR) across the 200 mg, 400 mg, and 800 mg
sovaprevir dose groups were 100%, 94% and 100%, respectively.
Today, the Company reported SVR4 rates of 90%; 85%; and 100% in the 200 mg,
400 mg, and 800 mg dose groups, respectively, after 24 weeks of therapy consisting of 12 weeks
of sovaprevir and P/R followed by additional 12 weeks of P/R. In all, 39
patients were assigned to receive an additional 12 weeks of P/R therapy with the
remaining 14 patients assigned to receive an additional 36 weeks of P/R.
** One patient withdrew for AE deemed unrelated to sovaprevir.
++ One patient withdrew consent, one patient moved, both undetectable at the time of
withdrawal; two patients withdrew for AEs deemed unrelated to sovaprevir.
* Two patients lost to follow-up, both undetectable at last assessment.
** One patient lost to follow up, undetectable at last assessment.
As previously reported, sovaprevir was generally well tolerated across all dose
groups. Adverse events (AEs) in patients receiving sovaprevir were classified as
mild to moderate and were transient. The most common AEs were consistent with
Additional clinical trial results, including SVR4 and
SVR12 for all patients treated with sovaprevir followed by an additional 12
weeks or 36 weeks of P/R, are expected be reported during the first quarter of
ACH-3102: Phase 1 trial in Healthy Volunteers and HCV-infected patients
In May 2012, Achillion initiated a Phase 1 clinical trial
evaluating the safety and tolerability of single and multiple ascending doses of
ACH-3102, a once daily, second-generation, pan-genotypic NS5A inhibitor, in
To date, 42 healthy volunteers have received a single
dose of ACH-3102, ranging from 25 mg to 1,000 mg. An additional 24 healthy
volunteers have received 14 days of once daily ACH-3102, with doses ranging from
25 mg to 75 mg. Preliminary data from both the single and multiple ascending
dose groups demonstrated that ACH-3102 was well tolerated at all doses
evaluated. There were no serious adverse events, no clinically significant
changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations.
All reported adverse events were classified as mild or moderate, and were
transient in nature.
Achillion announced today the initiation of enrollment of patients with genotype 1
HCV into a Phase 1 study to evaluate the safety, tolerability and antiviral activity
of ACH-3102. The trial will initially evaluate the safety and antiviral activity of a single
dose of ACH-3102. Initial results are expected to be reported during the third quarter
Conference Call Achillion will host a conference call and
simultaneous webcast on Wednesday, August 8, 2012 at 10:00 a.m. EDT. To
participate in the conference call, please dial (877) 266-0482 in the U.S. or
(631) 291-4565 for international callers. The conference call ID is 13643523. A
live audio webcast of the call will be accessible at www.achillion.com, under
the News Center section of the website. Please connect to Achillion's website
several minutes prior to the start of the broadcast to ensure adequate time for
any software download that may be necessary.
A replay of the webcast will be available on www.achillion.com .
Alternatively, a replay of the conference call will be available starting at 1:00 p.m. EDT
on August 8, 2012, through 11:59 p.m. Eastern time on August 15, 2012 by dialing
(800) 585-8367 or (404) 537-3406. The replay passcode is 13643523.
The hepatitis C virus is the most common cause of viral hepatitis, which is
an inflammation of the liver. It is currently estimated that more than 170 million
people are infected with HCV worldwide including more than 5 million people in the United
States, more than twice as widespread as HIV. Three-fourths of the HCV patient
population is undiagnosed; it is a silent epidemic and a major global health
threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage
that can result in the development of liver cancer, liver failure or death. Few
therapeutic options currently exist for the treatment of HCV infection. The
current standard of care is limited by its specificity for certain types of HCV,
significant side-effect profile, and injectable route of administration.
About Achillion Pharmaceuticals
Achillion is an innovative pharmaceutical company dedicated to bringing important
new treatments to patients with infectious disease. Achillion's proven discovery and
development teams have advanced multiple product candidates with novel
mechanisms of action. Achillion is focused on solutions for the most challenging
problems in infectious disease including HCV and resistant bacterial infections.
For more information on Achillion Pharmaceuticals, please visit
www.achillion.com or call 1-203-624-7000.
This press release includes forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 that are subject
to risks, uncertainties and other important factors that could cause actual
results to differ materially from those indicated by such forward-looking
statements, including statements with respect to the expected safety, efficacy
and potential benefits of sovaprevir, expectations about milestone achievement
including the potential to achieve proof-of-concept for ACH-3102 and initiation
of all-oral, interferon-free clinical trials evaluating regimens containing
sovaprevir (ACH-1625) and ACH-3102 for the treatment of HCV. Among the factors
that could cause actual results to differ materially from those indicated by
such forward-looking statements are risks relating to, among other things
Achillion's ability to: replicate in later clinical trials positive results
found in earlier stage nonclinical studies and clinical trials of its drug
candidates, including ACH-1625 and ACH-3102; advance the development of its drug
candidates under the timelines it anticipates in current and future clinical
trials; obtain necessary regulatory approvals; obtain patent protection for its
drug candidates and the freedom to operate under third party intellectual
property; establish commercial manufacturing arrangements; identify, enter into
and maintain collaboration agreements with appropriate third-parties; compete
successfully with other companies that are seeking to develop improved therapies
for the treatment of HCV; manage expenses; and raise the substantial additional
capital needed to achieve its business objectives. These and other risks are
described in the reports filed by Achillion with the U.S. Securities and
Exchange Commission, including its Annual Report on Form 10-K for the fiscal
year ended December 31, 2011 and its subsequent SEC filings.
In addition, any forward-looking statement in this press release represents
Achillion's views only as of the date of this press release and should not be relied upon
as representing its views as of any subsequent date. Achillion disclaims any
obligation to update any forward-looking statement, except as required by
CONTACT: Company Contact: Glenn Schulman Achillion
Pharmaceuticals, Inc. Tel. (203) 624-7000 firstname.lastname@example.org Media:
Christin Culotta Miller Ogilvy PR Tel. (646) 229-5178
email@example.com Investors: Mary Kay Fenton Achillion
Pharmaceuticals, Inc. Tel. (203) 624-7000 firstname.lastname@example.org Investors: Seth
Lewis The Trout Group, LLC Tel. (646) 378-2952 email@example.com Source: