- 现金
- 176 元
- 精华
- 0
- 帖子
- 112
- 注册时间
- 2015-5-14
- 最后登录
- 2016-11-12
|
箭头季报电话会议中关于ARC-520的部分
We also made good progress on the clinical program for ARC-520, our candidate against chronic hepatitis B infection. We had productive discussions with the FDA on our plans for a multi-dose study and received some valuable feedback about the program that has been incorporated in our plans for the U.S. as well as Europe and Asia.
In April, we gained clearance from the FDA to proceed with the Heparc-2004 clinical study with an initial dose of 1 mg/kg. We are pleased to be moving forward with that study here in the U.S., and expect that it will generate valuable data about ARC-520’s activity in a multi-dose setting.
Thus, our multiple dose Phase 2b studies remain on track and we expect to begin dosing patients in the US this quarter. We also believe that we may begin receiving approvals to start international studies this quarter, with dosing likely beginning in the summer.
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.
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.
|
-
总评分: 现金 + 10
查看全部评分
|