美国FDA批准Asterias 1/2a期脊髓损伤临床试验

tcaact

        新闻链接：http://www.dddmag.com/news/2014/ ... gin-stem-cell-trial+ I! E) A$ P$ d( a3 F
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新闻原文：- A& S' K: d) h. `9 Y* D
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FDA Clears Asterias to Begin Stem Cell Trial
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$ e1 z+ Y0 ?' O* GWed, 08/27/2014 - 3:08pm
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Asterias Biotherapeutics Inc. has received clearance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1/2a clinical trial of its product, AST-OPC1, in patients with complete cervical spinal cord injury.  The approved trial follows the successful completion of the Phase 1 clinical study of the product, and is designed to assess safety and activity of escalating doses of AST-OPC1 in patients with complete cervical spinal cord injuries, the first targeted indication for AST-OPC1 and the first of future product registration clinical trials.7 H& x% l. P, N  k$ ^6 ?

/ d: Q1 I0 c+ ]3 A' H1 W3 x“We would like to acknowledge the scientists, clinical investigators and FDA for working with us to develop AST-OPC1,” said Pedro Lichtinger, president and CEO of Asterias. “We are especially enthusiastic about working with our new partner, CIRM, in executing this clinical trial. The FDA clearance provides Asterias with imminent access to the previously announced $14.3 million CIRM grant, which provides non-dilutive funding to support both the clinical trial and other product development activities for AST-OPC1.”
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AST-OPC1 is a population of cells derived from human embryonic stem cells (hESCs) that contains oligodendrocyte progenitor cells (OPCs). OPCs and oligodendrocytes perform supportive functions for nerve cells in the central nervous system. The foundation for this newly cleared Phase 1/2a clinical trial comes from results from the Phase 1 clinical trial of AST-OPC1, which met its primary endpoints of safety and feasibility when administered to five patients with neurologically-complete, thoracic spinal cord injury. These five patients were administered a low dose of two million AST-OPC1 cells and have been followed to date for two to three years. No serious adverse events were observed associated with the delivery of the cells, the cells themselves, or the short-course immunosuppression regimen used.  There was no evidence of expanding masses, expanding cysts, infections, cerebrospinal fluid leaks, increased inflammation, neural tissue deterioration or immune responses targeting AST-OPC1 in these patients. In four of the five subjects, serial MRI scans performed throughout the two- to three-year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration.. S3 F( n( r  S1 ?% T1 U! }4 U
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The new Phase 1/2a clinical trial will be an open-label, single-arm study testing three escalating doses of AST-OPC1 in 13 patients with subacute, C5 to C7, neurologically-complete cervical spinal cord injury. These individuals have essentially lost all sensation and movement below their injury site with severe paralysis of the upper and lower limbs. AST-OPC1 will be administered 14 to 30 days post-injury. Patients will be followed by neurological exams to assess the safety and activity of the product.  Selection of the clinical trial sites is well underway and the Company expects to begin patient enrollment during the first quarter of 2015.
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The new clinical trial differs from the original clinical study in that doses up to 10 times higher will be tested.  In addition, the trial will focus on patients with neurologically-complete cervical spinal cord injuries.  Because of the anatomy of the spinal cord and the existence of more sensitive outcomes measures to assess movement of the arms and hands, it is currently believed that detection of efficacy is much more likely to occur in patients with cervical injuries. It is this patient population that Asterias anticipates will be the target for the first registration clinical trials of AST-OPC1. The results of the Phase 1/2a clinical trial are expected to provide support for a Phase 2b expansion study that will be conducted to more thoroughly demonstrate safety and efficacy of the product.
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Date: August 27, 2014% B% a# W) f4 L
Source: Asterias Biotherapeutics

Damon-Salvatore

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7 N5 D: J: ]! a7 G- `% XI  got a few questions as follow,+ ]  u( N, f6 p1 I
1. Where do the hESCs come from? SCNT or deprived from abortion fetus?+ O5 O, R2 B( d  X- ^. ?
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2. how to overcome the immune rejection? If the hESCs are obtained via abortion fetus, that's to say we're gonna inject allogenetic cells with different MHC II, which would trigger rejection. And I've noticed that even in the autologous cell therapy, SCNT occasion, the MHC II expression would change after injection in the complicated niche in patients. It's mentioned that  short-course immunosuppression regimen is used. SO the regimen won't follow the whole life of patients?
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+ d+ e5 M+ S3 j3. Is there an economical protocol available to expand the AST-OPC1?  million class of cells would be needed for injection.; E+ E& y4 j8 i$ w  \( S" j

( c  ~' E! x& i* x+ yI'd appreciate it a lot if some relevant and latest paper is uploaded.

草胞

FDA是按新药批准的，还是按产品批准的呢？这个怎么看啊？请高手指教

tcaact

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回复 Damon-Salvatore 的帖子
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    都是很好的问题。
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( Q% G. y$ }' s" e$ O8 a    估计需要询问Asterias那边。这是其官网对AST-OPC1 cells的描述：http://asteriasbiotherapeutics.com/our-clinical-focus/opc1/， 但估计还是无法回答你的问题。
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    另，找到一篇对Asterias R&D 主管的interview：http://www.ipscell.com/2014/08/i ... ed-stem-cell-trial/
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Interview with Jane Lebkowski on Asterias FDA-approved Stem Cell Trial
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Posted on August 28, 2014: L& l3 ~( o8 M  E' ?4 \' N9 z

* ]! K% U. n1 d2 C5 S) oThe BioTime subsidiary, Asterias, has received FDA approval for a combined Phase I/IIa clinical trial of OPC1 for treating spinal cord injury.' K8 M/ U, i% _
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BioTime (BTX) and Asterias (ASTY) have picked up the portfolio of the former Geron clinical trial using oligodendrocyte precursor cells (OPC). Asterias also acquired a second element from Geron in the form of a lung cancer treatment based on stem cells that sounds quite intriguing.
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To learn more about this exciting news I interviewed Jane Lebkowski, President of Research and Development at Asterias.' ?9 c6 R( K9 ]& z. u. z9 T% k
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1. What are the most important things for the stem cell community to know about Asterias getting the FDA approval to move forward with this Phase 1/2a trial?$ ^# N, g8 y0 E; d
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Lebkowski: There are a couple of very interesting points.1 [# w+ r9 L3 l1 ]" p- u3 W

; ~8 _* P2 C1 EIn the first clinical trial by Geron, safety was established in patients with thoracic spinal cord injury. Now, with this current FDA clearance and the new clinical protocol, we will test AST-OPC1 in a different patient population, those patients with complete cervical spinal cord injuries. We think this population will be the first target for registration trials for AST-OPC1. Patients with cervical injuries have more extensive paralysis involving both the lower and upper limbs. Because of both the anatomy of spinal cord in the cervical spinal cord region and superior ways to assess restoration of upper body movement, we believe testing of AST-OPC1 in this patient population will provide a better opportunity to assess potential clinical benefit of the cells.
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& J/ Y6 l8 f3 S9 N2 [5 {Another important point of the new trial is that will test escalating doses of AST-OPC1. The first clinical trial performed by Geron tested a single low dose of the cells. In the new Phase 1/2a trial, we will escalate doses into the range where we feel we can see potential clinical activity., `. a. Q2 D0 d0 q

$ E  a( E3 l/ _& Y* p2. What are the doses in the new trial versus the original one?
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Lebkowski:  The dose used in the Geron trial was 2 million cells. The new trial will start with a dose of 2 million cells in the first cohort and then escalate to doses of 10 and 20 million cells in cohorts 2 and 3.
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! j$ ~  I9 o2 {# ~0 K: G0 p+ q3. The patients that originally received OPC1 when Geron was starting things have now been followed for a relatively long time. How are they doing?% H8 _, ?8 E* F* {. E( @8 b

$ _" P$ I$ Z/ Z% f/ {$ Y/ xLebkowski:   There have been no safety problems observed in these patients that were associated with the cells, injection of the cells, or immunosuppression used in the first clinical trial. We haven’t seen measurable neurological improvements in the patients, however these patients were administered only a low dose of cells. Importantly, there were no immune responses observed which targeted the cells. By MRI, there were indications of tissue sparing effects (reduced cavitation) in four out of the five patients in the original trial.
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The device and procedure used to administer the cells in cervical spinal cord injury patients are essentially the same as those used in the first trial in thoracic injury patients., p/ ^- x  `" S! |3 U
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When the product was owned by Geron, it was referred to as “GRNOPC1”.  It is now called “AST-OPC1” to reflect its new owner, Asterias Biotherapeutics.6 m) s# s$ K9 N0 X+ u
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4. What does the involvement of CIRM mean for the whole process?
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( D2 @- a; X1 E; yLebkowski:  CIRM will be helping to co-fund this new clinical trial. This funding can now be activated with the FDA clearance.
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5. What will the time course be like for this trial? 2 A- O3 b5 y* f5 z' B

% R- E3 Q; B' M$ KLebkowski:  We plan to start the trial in early 2015 with data becoming available as the trial progresses through the cohorts.
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6. In a broad sense, what does this clearance and the trial mean?/ K4 [8 k2 h, g( m. b4 `( K: G: w, q8 o! U) D
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Lebkowski:  Although the first trial was small, a good safety profile was established enabling more advanced testing of AST-OPC1 in clinical trials where both safety and efficacy can be potentially measured. The clearance also shows more broadly that human embryonic stem cell based therapies are progressing in their development. The field is advancing beyond the feasibility stage now.2 n$ `% U! z$ _3 U- F' y- ~  M

( o7 Y$ @) r! _& }0 j  ~8. Can you tell us briefly about Asterias’ lung cancer program?+ C5 j/ L9 c( s5 O$ ~

  Z2 c8 R* H' GLebkowski:  A second Asterias product is AST-VAC2, which are human embryonic stem cell derived dendritic cells. These cells are modified to express telomerase, a protein typically expressed in cancer cells. The aim is to use these telomerase expressing dendritic cells to stimulate immune responses against cancer cells. We are now preparing for clinical trials with this product.

melodyboy007

有没有中文的

liuxiao2006

受益匪浅！