Terminated PD Experimental Treatments 2004 - present
GDNF (Neurotrophic factor) – recombinant GDNf delivered by pump
infusion method
Sponsor: Amgen, Inc.
Phase II trials terminated in September
2004.
Comments: Amgen announced in
June 2004 that, “Six
months of treatment with GDNF delivered to the putamen failed to improve
UPDRS scores compared to placebo. There was “evidence of alteration of brain
function,” a likely reference to changes on neuroimaging, but improvement on
UPDRS scores did not meet the primary endpoint of the trial.
Initially, Amgen announced that all subjects were entered in an open label
extension study to resolve differing trial results. But in Sept. 2004,
Amgen sent letter to clinical investigators halting further clinical
studies, due to safety concerns – development of lesions in the cerebellum
of 4 test monkeys and "anti-r-metHuGDNF neutralizing antibodies found in
two of the study participants to date.”
CEP-1347 (Kinases Inhibitor)
Sponsor: Cephalon, Inc.
Phase II / III Trial discontinued in
May 2005
Comments: “The study was concluded early, after an average of 21.4
months of follow-up, when a planned interim analysis demonstrated that it
would be futile to continue experimental treatment. In contrast to research
in animal models that predicted favorable disease-modifying outcomes, we
found CEP-1347 to be an ineffective treatment in early Parkinson disease. "
NS2330
(Monoamine Uptake Inhibitor)
Sponsor: Neurosearch, Inc.
Phase III canceled Jan. 2006
Comments: "Results from three comprehensive Phase II studies in
Alzheimer’s and Parkinson’s diseases with tesofensine (NS2330) did not meet
the criteria we had defined together with our partner Boehringer Ingelheim
for starting up Phase III clinical studies. Boehringer Ingelheim terminated
the tesofensine partnership in January 2006." Further development for PD has
been halted.
GPI 1485 (Neuroimmunophilin Ligand))
Sponsor:
Symphony Neuro Development Company
Phase
III terminated in March 2006
Comments: In March 2006 citing
a lack of evidence of clinical benefit, Symphony Neuro Development Company
stopped further drug treatment in its open-label study of GPI 1485 in
Parkinson’s disease patients who had previously participated in the
completed 2 year double blind efficacy study .
Phase
III was not initiated..
"While the treatment was well tolerated and posed no significant safety
issues, the treatment group failed to show an improvement in the primary
endpoint of the trial which was percent change of baseline of brain uptake
of [123I}Beta-CIT as measured by SPECT Scanning, a measure of the brain
dopamine system that degenerates in Parkinson’s disease.... In addition,
none of the exploratory clinical endpoints showed clinically meaningful
benefit after 24 months of therapy....”
E2007 (perampanel
) (AMPA
receptor antagonist)
Sponsor: Eisai
Inc.
Phase III trials terminated in Oct. 2007 and April 2008.
Comments: “In Oct. 2007, Eisai announced one of its Phase III studies
(#301) "did not meet its primary endpoint comparing perampanel (E2007) to
placebo as an add-on to levodopa therapy for 764 idiopathic Parkinson's
disease patients over 30 weeks. The primary endpoint was reduction in "off"
time - defined as the length of time that Parkinson's symptoms return as the
effect of levodopa wears off. Perampanel was well tolerated with no
significant safety issues... Two additional Phase III studies (#302 and
#309) will proceed as planned."
“ In April 2008, following the
completion of two Phase III Studies , Eisai decided to discontinue their PD
research program for E2007. The sponsor reported the studies "did not show a
significant difference in the primary endpoint of reduction of "off" time
...the third Parkinson's disease Phase III study and open label treatment
extension studies" were also terminated. “
Sarizotan (EMD 128130) - (Dopamine Agonist)
Sponsor: Merck KGaA
Phase III terminated in June 2006.
Comments: “Double-blind Phase III studies did not confirm Phase II
results or results from preclinical studies. In June 2006, "Merck KGaA
decided, after analysis of data from Phase III clinical trials not to file
for approval and not to pursue further development of the compound. Merck
said a statistically significant difference between sarizotan and placebo
could not be demonstrated in the late-stage clinical studies."
Vadova
(IPX054) -Levodopa
Sponsor:
IMPAX Laboratories, Inc.
Received “non-approvable letter from FDA in March 2006, and Jan. 2008.
Sponsor terminated development in April 2008
Comments: The FDA issued IMPAX a "Non-approvable letter in March 2006,
but Impax filed more papers to answer regulators' concerns. The FDA rejected
the drug again in January 2008, saying this time the drug could be confused
with other marketed versions of carbidopa/levodopa and could lead to
medication errors."
Istradefylline (KW- 6002) - (Adenosine
Receptor Antagonist)
Sponsor: Kyowa
Pharmaceutical, Inc.
Phase III development suspended in
North America in June 2008.
Comments: On June 3, 2008, Kyowa Pharmaceutical, suspended the development
of istradfeylline in North America. A letter from the company President
stated, "On February 25, 2008, Kyowa received a “Not Approvable” letter from
the U.S. Food and Drug Administration (FDA) for istradefylline and
subsequently had discussions with the FDA about options for further
development. After reviewing these options, Kyowa has decided to suspend
development of istradefylline in North America at this time. This decision
was not related to any safety issues concerning istradefylline." "According
to Dr. Mark Stacy, the trial may not have been optimally designed to reflect
istradefylline's true efficacy. While at first glance the 12% to 14%
reduction in "off" time from baseline appears "disappointing," Dr. Stacy
said it must be kept in mind that the vast majority of these patients had
advanced motor scores and were being treated with 2 or more drugs. In
addition, although the trial's enrollment criteria required that patients
have a minimum of 2 hours of "off" time per day, Dr. Stacy said once the
data were analyzed, the researchers found that the average amount of "off"
time in study subjects was 6 hours every day….Furthermore, he said, the
measurement tool used to determine "off" and "on" time was likely not
sensitive enough. "If we'd used a more precise tool we'd probably have
bubbled up better data," he said.
Source: Medscape News, June 5, 2008
Spheramine (Retinal
Pigmented Epithelial (RPE) Cells)
Sponsor:
Bayer-Schering / Titan
Bayer discontinued development of
Spheramine in July 2008.
Comments:
Titan announced in July 2008 that its "potential cell-based treatment for
Parkinson's Disease failed to meet its primary and secondary endpoints in a
Phase IIb study, and likely won't be continued by partner Bayer Schering
Pharma... Initial analysis of results from the 71-patient study of
Spheramine -- designed to test the safety, tolerability and efficacy of the
treatment -- found that it had no significant differences from sham surgery
arms after 12 months of follow up." (Company press release 7/2/08)
CERE-120
(neurturin) – Gene therapy
Sponsor: Ceregene
Phase II trial failure announced in Nov.
2008.
Comments:
Ceregene announced the phase
II trial did not demonstrate an appreciable difference between patients
treated with CERE-120 versus those in the control group. Both groups showed
an approximate 7 point improvement in the protocol-defined primary endpoint
(Unified Parkinson’s Disease Rating Scale- motor off score at 12 months),
relative to a mean at baseline of approximately 39 points. Both groups had a
substantial number of patients who demonstrated a meaningful clinical
improvement from baseline. CERE-120 appeared to be safe and well tolerated."
…A company spokesman stated "...we are
stunned by the results of this trial and will continue to analyze the data
in order to gain greater insight into the factors that may have contributed
to this negative outcome, not only to build upon this insight for our
Parkinson’s program, but also to help assure continued successful
development of our product candidates for other diseases.”
(company press release 11/28/08)
PD Drugs
approved by FDA 2004 - present
Azilect (Rasagiline) (MAO –B inhibitor) - approved for early PD.
Neupro Rotigiotine transdermal system (patch) – reformulation of
dopamine agonist. All patches recalled indefinitely in North America due to
manufacturing problem.
Parcopa – reformulation -
orally disintegrating carbidopa/levodopap tablets Requip XL (once-a-day) – Reformulation of dopamine agonist
Zelapar – dissolving tabs – reformulation of seligiline
Source:
Parkinson Pipeline Project, Treatments in Development database
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