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newchinabok 发表于 2015-6-18 15:21 
回复 StephenW 的帖子
大猩猩新数据新在何处，3mg，4mg为何收集数据要半年？为何fda要数据也不给？ ...
May 11 2015
As we have said in the past, we are true pioneers in HBV. Everything we learn in
clinical and non-clinical studies helps shape our strategy for the indication, and
much of what we are doing represents firsts for the field. Of course this is
extremely helpful to us, but it also introduces real questions relating to
communication strategy in light of competitive considerations. We have been
fairly quiet about the program since presenting early data at AASLD, which, I
might add, was notable because only a single initial dose of ARC-520 elicited what
we believe to be the first reliable report of significant s-antigen reduction in
humans. This relatively quiet period does not mean that we were idle. To the
contrary, we have been very busy and have learned a tremendous amount about
ARC-520 and the hepatitis B virus. Here is what we are prepared to disclose at
this time.
For the first time we can report that we have been conducting a long-term study of
ARC-520 in 9 chimpanzees chronically infected with hepatitis B. It has been
going on for about a year and is nearing completion. We believe this to be the
largest and longest study ever conducted in chronically infected chimpanzees and
certainly the most exhaustive study to date with ARC-520. We have generated a
large amount of very exciting data, and we are not yet finished. I believe this study
will advance the entire field of HBV and it has been very important in advancing
our understanding of how ARC-520 may fit into a treatment strategy.
The wealth of data the chimp study and single dose Phase 2a study have provided
very important insights into the drug and disease, some of which challenge current
dogma. To date we have not spoken publically about any of this chimp data.
These studies have led to new hypotheses, and we have decided to test some of
these new hypotheses in humans by adding 3 cohorts to the Phase 2a study in Hong
Kong, which remains blinded. None of these employ doses greater than 4 mgs per
kg, and two are open label while the third is a double blind placebo controlled
cohort. These are important groups and we are very excited about completing
them. We have said repeatedly in the past that this program would be iterative in
nature and that we would follow the data. This is an example of that flexible
stance. Unfortunately, because one of the new cohorts is placebo-controlled, this
will mean pushing back unblinding of the entire study to next quarter rather than
this quarter.
I appreciate that some will be disappointed that we are changing guidance for
release of the 3 and 4 mg/kg results from 2nd to 3d quarter, but we did not
anticipate expanding the Hong Kong study when we set that guidance. Our
regulatory team and advisors agree that unblinding the study once all of the blinded
cohorts have run their course is the prudent course of action under these
circumstances to maintain the integrity of the studies in the eyes of the scientific
community and international regulatory authorities. It is simply unwise, and
frankly uncommon in the pharmaceutical industry, to unblind cohort-by-cohort
without a compelling reason to do so, such as our decision to unblind the first two
cohorts in preparation for an FDA filing. I strongly believe that our long term
chimp study will be considered seminal HBV work, and it has enabled us to build a
more complete Phase 2a study in humans. This is all great news for the field and
the Company, so a 1-quarter delay in data release is a small price to pay when we
are focused on creating durable long-term value.
We will have a tremendous amount of data to report between the 7 cohorts of
patients in the enlarged Phase 2a and the greater than 1-year study of 9 chronically
infected chimps. Because of the quantity and importance of these data, we will
have an analyst day next quarter to present the findings in detail. We plan on
having not only our scientists participate, but also internationally recognized
experts in the field. It will be an important event for us and I also believe it will be
an important event for the entire HBV field.
With that overview, I would now like to turn the call over to our COO and Head of
Development, Dr. Bruce Given. Bruce?
Bruce Given
Thank you Chris and good afternoon everyone.
As you heard from Chris, our clinical development and regulatory teams have been
very busy recently and are doing great work designing and managing our clinical
studies. Chris touched on this, but I would like to talk for a moment about the
Heparc-2001 study of ARC-520. As you recall, this was originally a single-dose
Phase 2a study in e-antigen negative chronic HBV patients at two sites in Hong
Kong. We previously reported initial results from the first two dose cohorts at 1
and 2 mg/kg, and as of our last quarterly conference call we had enrolled an
additional two dose cohorts at 3 and 4 mg/kg. Observation periods are complete
for these, and the cohorts remain blinded. We have since made protocol
amendments to add three additional cohorts, two of which have already received
IRB approval to proceed, and we expect the third to be approved as early as this
month. We have already enrolled and dosed 7 of 8 patients in the first new cohort
and hope to dose the last patient shortly. The second additional cohort is recruiting
patients now. Similarly, we expect the third new cohort to enroll at a good pace
once IRB approval is achieved.
As you know, we unblinded the 1 and 2 mgs per kg cohorts early in order to
support an IND and other regulatory filings for multiple dose Phase 2b studies.
We expect to unblind the entire Phase 2a study, which will include the 3 and 4 mgs
per kg cohorts as well as the additional blinded cohort, next quarter. We
understand that many would like us to disclose data from the 3 and 4 mgs per kg
cohorts now, and we would also like to be able to discuss those. However,
unblinding cohorts for the sake of eager curiosity is not the right way to run a
development program. This is a marathon not a sprint, and we need to ensure the
long-term integrity of the program and studies that may ultimately support
regulatory approval. We are committed to following GCP standards and
regulatory norms in order to ensure as smooth a regulatory process as possible.
As Chris mentioned, we have already generated a great deal of information in the
long-term chimp study and the now expanded Phase 2a that we believe will prove
important for the HBV field. Once we are able to unblind the entire Phase 2a next
quarter, we will have an in depth analyst day to discuss these data along side of the
long-term chimp data. We expect to host internationally recognized KOLS as part
of this event. Given the scope of the data, we believe that several important
presentations and peer-reviewed articles will emerge from these studies, in addition
to what is reported at the analyst day. This will be an exciting time for us. Stay
tuned.
Turning to the multiple-dose Phase 2b studies of ARC-520, we received clearance
from the FDA to proceed with the Heparc-2004 study in the US. This is a
multicenter, randomized, double-blind, placebo-controlled, multi-dose study of
ARC-520 administered intravenously to patients with chronic immune active HBV
infection maintained on entecavir or tenofovir therapy. The study is planned to
enroll up to 12 patients who will be randomized at a ratio of 2:1 with 8 patients
receiving 1 mg/kg of ARC-520 and 4 patients receiving placebo. Each patient will
receive 3 total doses, once every 4 weeks. Patients will be followed through Day
147.
The primary objective of Heparc-2004 is to evaluate the depth of hepatitis B
surface antigen decline in response to multiple doses of ARC-520 compared to
placebo.
We intend to open three sites for enrollment. One site was opened for enrollment
last week and patient screening has begun. Site initiation for the other two is
scheduled for the coming weeks and then they may begin recruiting and screening
patients.
As we have mentioned before, we still intend to proceed with additional core
international multi-dose trials. We have incorporated the FDA recommendations,
which were constructive and cost sparing to the program overall, into our
international regulatory filings which have been submitted during the last couple of
months. We are working diligently with regulators in select European and Asian
countries now, and we intend to provide an update publicly after we have been
cleared to proceed. |
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楼主: StephenW
发表于 2015-6-18 01:59
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