UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of Earliest Event Reported): November 14, 2011
Aastrom Biosciences, Inc.
(Exact name of registrant as specified in its charter)
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Michigan |
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000-22025 |
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94-3096597 |
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(State or other jurisdiction |
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(Commission |
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(I.R.S. Employer |
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of incorporation) |
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File Number) |
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Identification No.) |
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24 Frank Lloyd Wright Drive, P.O. Box |
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48106 |
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(Address of principal executive offices) |
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(Zip Code) |
Registrant’s telephone number, including area code: (734) 418-4400
Not Applicable
Former name or former address, if changed since last report
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Item 7.01. Regulation FD Disclosure.
On November 14, 2011, Aastrom Biosciences, Inc. (the “Company”) presented 12-month final data from the RESTORE-CLI Phase 2 clinical trial of ixmyelocel-T in the treatment of critical limb ischemia patients with no revascularization options. The results were presented by William Marston, M.D., chief, Division of Vascular Surgery, and professor, Department of Surgery, University of North Carolina, in an oral presentation at the 2011 American Heart Association Scientific Sessions in Orlando, FL, a copy of which is furnished herewith as Exhibit 99.1.
Item 8.01. Other Events..
On November 14, 2011, the Company issued a press release, a copy of which is attached hereto as Exhibit 99.2 and is incorporated herein by reference.
Item 9.01. Financial Statements and Exhibits.
Exhibit 99.1. Slide presentation dated November 14, 2011
Exhibit 99.2. Press release dated November 14, 2011
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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Aastrom Biosciences, Inc. | |
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Date: November 14, 2011 |
By: |
/s/ TIMOTHY M. MAYLEBEN |
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Name: Timothy M. Mayleben |
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Title: Chief Executive Officer and President |
Exhibit Index
99.1 Slide presentation dated November 14, 2011
99.2 Press release dated November 14, 2011
Exhibit 99.1
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Patient-Specific Cellular Therapy (Ixmyelocel-T) is Safe and Improves Time to Treatment Failure in Patients with Critical Limb Ischemia and No Revascularization Options American Heart Assoc Scientific Sessions 2011 William Marston MD For the RESTORE-CLI Clinical Investigators Orlando, FL November 14, 2011 |
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RESTORE-CLI Investigators Scott Berceli W Todd Bohannon Anthony Comerota Carlo Dall’Olmo Raul Guzman Brian Halloran Peter Henke Timothy Henry Colleen Johnson William Marston Jeff Martinez Farrell Mendelsohn Richard Powell Jorge Saucedo Patrick Stiff Edith Tzeng Omaida Velazquez |
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Disclosures William Marston, MD TITLE: Chief, Division of Vascular Surgery Professor, Department of Surgery University of North Carolina FINANCIAL DISCLOSURE: Aastrom (Consultant/Advisory Board) |
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Ixmyelocel-T: Description Autologous (patient-specific), expanded multicellular therapy Target population: CLI patients with no options for revascularization Cell source: Bone marrow Cell delivery: Twenty intramuscular injections in lower extremity |
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Ixmyelocel-T Production 5 Bone marrow (approx. 50ml / 3 tablespoons) is taken from patient’s hip 15 minute outpatient procedure automated system expands key beneficial cell types Expanded multicellular therapy is administered to the same patient 20 minute in-office procedure for CLI patients Day 1 Days 2-13 Day 14 Extract Bone Marrow Expand Cell Population Administer to Patient |
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Ixmyelocel-T Cell Expansion 6 Starting Bone Marrow Red Blood Cells Lymphocytes T + B Granulocytes Monocytes Mesenchymal Stem Cells CD45 Aastrom Proprietary Expansion Process ixmyelocel-T Therapeutic Effect RBC extraction < 0.1% remaining Cell Reduction Cell Amplification -5X -5X +200X +50X ~300 million cells ~150 million cells Remodelling of ischemic tissue Modulation of inflammation Promotion of angiogenesis CD 14 Macrophage CD90 |
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Ixmyelocel-T Has Multiple Biological Activities Remodeling of tissues Secretion of MMPs Phagocytosis and efferocytosis Contraction of ECM Promotion of angiogenesis Secretion of angiogenic cytokines Activation of eNOS Resolution of inflammation Secretion of anti-inflammatory cytokines Alternatively activated macrophages 7 |
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Phase 2b RESTORE-CLI Study Design Randomized, placebo controlled Double-blind Powered as Phase 2 safety study 150 patients 18 active centers No-option CLI patients who had rest pain with or without baseline wounds 7 |
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Key Inclusion Criteria Age 18-90 Diagnosed CLI Ischemic rest pain > 2 weeks duration Ulceration or gangrene of toe or foot Toe systolic pressure < 50 mmHg Ankle systolic pressure < 70 mmHg Infrainguinal occlusive arterial disease judged not amenable to revascularization 8 |
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Key Exclusion Criteria Previous amputation at talus or above Failed ipsilateral revascularization within 2 weeks of randomization Active infection of target extremity HbA1C > 10% Untreated aorto-iliac occlusive disease Exposed tendon or bone in wound 9 |
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Study Protocol 2:1 randomization ixmyelocel-T placebo injection (acellular vehicle) One-time set of 20 intramuscular injections 0.5 ml each Lower thigh Calf Foot 12 month follow-up 10 |
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Defined Study Outcomes Safety population: all pts randomized and aspirated Efficacy population: all pts randomized, aspirated and treated Primary (safety): All adverse events Primary efficacy: Time to first occurrence of treatment failure (TTF) Major amputation of treated leg All-cause mortality Doubling of wound total surface area from baseline De novo gangrene Secondary: Amputation-free survival (AFS) Major amputation of treated leg All-cause mortality 11 |
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RESTORE-CLI Results: Patient Flow Based on interim analysis, randomization stopped at 86 patients 9 withdrew prior to aspiration 77 aspirated 72 received treatment injections 48 ixmyelocel-T 24 placebo control 12 |
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13 * All 3 patients had a major amputation prior to withdrawing from the study. Ixmyelocel-T N = 48 Control N =24 Completed 39 (81) 21 (88) Died 3 (6) 2 (8) Withdrew 6 (13) 1 (4) -w/endpoint* 3 (6) 0 (0) -w/o endpoint 3 (6) 1 (4) Patient Disposition – All Treated Patients (n=72) |
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Parameter* (Mean values) Ixmyelocel-T N = 48 Control N = 24 % Male 71 58 Age 69 67 % Current, % Past smokers 17, 67 38, 46 % Current, % Past alcohol 44, 23 29, 33 BMI 27 28 Creatinine mg/dL 1.2 1.1 N (%) with known Diabetes 21 (44) 15 (63) Patient Demographics– All Treated Patients (n=72) *No significant differences 15 |
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Time to First Occurrence of Treatment Failure – All Treated Patients (N=72) 62% risk reduction: HR 0.38, 95%CI = (0.20-0.74) 15 |
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First Event Contributed to Treatment Failure – All Treated Patients (N=72) Ixmyelocel-T N = 48 Control N = 24 Endpoint (n) Major amputation 6 4 All-cause mortality 2 1 Doubling in total wound surface area* 5 7 De novo gangrene 6 4 Total n(%) 19 (39.6%)** 16 (66.7%)** *For wound size doubling: patient must have come into the study with a wound to be eligible to contribute to this event. ** p = 0.0451, Fisher’s exact test. 16 |
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Amputation-Free Survival – All Treated Patients (N=72) 32% risk reduction: HR 0.68, 95%CI = (0.28-1.65) 17 |
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18 Patients with Baseline Wounds – 45 of 72 treated patients Ixmyelocel-T: 29 / 48 patients (60.4%) Control: 16 / 24 patients (66.7%) Repeat analysis for only those patients with baseline wounds TTF AFS Post Hoc Analysis – Patients with Baseline Wounds |
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TTF and AFS – Baseline Wound Patients (N=45) 19 77% risk reduction: HR = 0.225 95% CI = (0.103, 0.490) Cox PH p-value for treatment = 0.0002 61% risk reduction: HR = 0.391 95% CI = (0.131, 1.164) Cox PH p-value for treatment = 0.0915 |
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20 Safety Overview: All Aspirated Patients (N=77) Safety Parameter Ixmyelocel-T N = 53 Control N = 24 P-value** N (%) with Adverse Events 47 (89) 23 (96) 0.424 N (%) Serious Adverse Event 23 (43) 12 (50) 0.628 N (%) withdrawal due to AE 2 (4) 0 (0) 1.000 N (%) Deaths * 3 (6) 2 (8) 1.000 * An additional ixmyelocel-T patient died ~100 days after completing study. ** Based on Fisher’s Exact Test. 20 |
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21 21 Safety Overview: AEs in > 10% of Aspirated Patients Preferred Term n (%) Ixmyelocel-T N = 53 Control N = 24 P-value** Pain in extremity 17 (32) 4 (17) 0.181 Gangrene 7 (13) 6 (25) 0.209 Cellulitis 5 (9) 6 (25) 0.087 Skin Ulcer 6 (11) 5 (21) 0.303 Hypertension 6 (11) 2 (8) 1.000 Nausea 5 (9) 3 (13) 0.699 ** Based on Fisher’s Exact Test. |
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Summary: RESTORE-CLI Safety profile for aspiration, injection and treatment with ixmyelocel-T favorable No increased adverse events compared to placebo TTF primary endpoint positive Significantly fewer adverse limb events 32% reduction in AFS in all treated patients Not significant difference Study not powered for AFS outcome Patients with baseline wounds had more pronounced treatment effect 22 |
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Ixmyelocel-T Development Plan: Phase 3 REVIVE – CLI 594 no-option CLI patients with tissue loss followed for 18 months Primary Efficacy Endpoint: AFS at 12 months 80 sites (site selection ongoing); US only 1:1 randomization to ixmyelocel-T or placebo Special Protocol Assessment (SPA) concurrence with FDA on trial design, endpoints, and statistical analysis plan Screening/enrollment initiation expected 4Q 2011 24 REVIVE – CLI |
Exhibit 99.2
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Aastrom Biosciences |
FOR IMMEDIATE DISTRIBUTION
Aastrom Reports Positive 12-Month Results from the RESTORE-CLI Phase 2
Clinical Trial for Ixmyelocel-T in Patients with Critical Limb Ischemia
Results presented today at the American Heart Association Scientific Sessions show
ixmyelocel-T met primary safety and efficacy endpoints in CLI patients with no
revascularization options.
ANN ARBOR, Mich., [November 14, 2011] - Aastrom Biosciences, Inc. (Nasdaq: ASTM), the leading developer of patient-specific, expanded multicellular therapies for the treatment of severe, chronic cardiovascular diseases, today reported positive 12-month final results from the RESTORE-CLI Phase 2 clinical trial of ixmyelocel-T in the treatment of critical limb ischemia (CLI) patients with no revascularization options. The results were presented today by William Marston, M.D., chief, Division of Vascular Surgery, and professor, Department of Surgery, University of North Carolina, in an oral presentation at the 2011 American Heart Association Scientific Sessions in Orlando, FL.
The randomized, double-blind, placebo-controlled, multicenter study assessed the safety and efficacy of ixmyelocel-T, a patient-specific, expanded multicellular therapy for the treatment of CLI, in a group of 72 patients at one year after treatment. Patients in the treatment arm showed a 62% reduction in risk relative to placebo in the primary efficacy endpoint of time to first occurrence of treatment failure (p = .0032). Treatment failure was defined as the first occurrence of any one of the following: major amputation of the treated leg, all-cause mortality, doubling of wound total surface area from baseline, or de novo gangrene. While the study was not powered to show statistical significance in the secondary endpoint of amputation-free survival (AFS; major amputation of the treated leg or all-cause mortality), results from a subgroup of 45 patients with wounds at baseline showed a positive trend in this measure (21% ixmyelocel-T treated vs 44% control event rate; p = 0.0802). The study also met the primary safety endpoint with no differences between the treated and control groups.
“These results provide substantial additional evidence that treatment with ixmyelocel-T significantly reduces the risk of disease progression for CLI patients with no options for
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revascularization. Importantly, the efficacy results demonstrate concordance across all of the defined measures of treatment failure in the trial,” said Dr. Marston. “In addition, the results related to AFS in the subgroup of patients with tissue loss similar to those who will be studied in the upcoming pivotal Phase 3 clinical trial show a strong and clinically relevant positive trend for such a small number of patients. These results are especially encouraging since the primary endpoint for the planned REVIVE-CLI pivotal Phase 3 clinical trial for ixmyelocel-T in no-option CLI patients will be amputation-free survival.”
The RESTORE-CLI Phase 2 clinical trial involved 72 CLI patients treated at 18 active centers in the United States. Patients were randomized 2:1 treatment versus placebo. Patients were treated with a one-time course of 20 intra-muscular injections in the lower thigh, calf and foot and were then followed for 12 months.
Forty percent of patients treated with ixmyelocel-T in this study had a treatment failure event compared to 67% of patients in the placebo group (a statistically significant risk reduction of 62%, p =.0032). In addition, 29% of the placebo group in the trial experienced their first event to be a doubling in total wound surface area from baseline in comparison to 10% of patients treated with ixmyelocel-T. Among patients whose first treatment failure event was de novo gangrene, the median time that patients treated with ixmyelocel-T reported the event was day 205 of the study, while the median time that patients in the placebo group reported the event was day 19 of the study (a difference of 186 days).
Aastrom will initiate the REVIVE-CLI Phase 3 clinical trial for ixmyelocel-T this quarter. The study will include 594 CLI patients with no option for revascularization and existing tissue loss. The primary endpoint of this study will be amputation-free survival at 12 months. Patients will be followed for a total of 18 months from the time of treatment.
“The 12-month results from our RESTORE-CLI Phase 2 clinical trial provide compelling clinical evidence that ixmyelocel-T could represent a major advance in the treatment of patients with CLI who have no option for revascularization. We look forward to initiating our pivotal Phase 3 clinical trial for ixmyelocel-T this quarter,” said Tim Mayleben, Aastrom’s president and chief executive officer.
The presentation slides will be available on the Aastrom web site today at http://investors.aastrom.com/events.cfm.
About Aastrom Biosciences
Aastrom Biosciences is the leader in developing patient-specific, expanded multicellular therapies for use in the treatment of patients with severe, chronic cardiovascular diseases.
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The company’s proprietary cell-processing technology enables the manufacture of ixmyelocel-T, a patient-specific multicellular therapy expanded from a patient’s own bone marrow and delivered directly to damaged tissues. Aastrom has advanced ixmyelocel-T into late-stage clinical development, including a planned Phase 3 clinical program to study patients with critical limb ischemia and two Phase 2 clinical trials in patients with dilated cardiomyopathy. For more information, please visit Aastrom’s website at www.aastrom.com.
Media contact
Bill Berry
Berry & Company
bberry@berrypr.com
(212) 253-8881
Investor contact
Danielle Spangler
The Trout Group
dspangler@troutgroup.com
(646) 378-2924
This document contains forward-looking statements, including, without limitation, statements concerning clinical trial plans and progress, objectives and expectations, clinical activity timing, intended product development, the performance and contribution of certain individuals and expected timing of collecting and analyzing treatment data, all of which involve certain risks and uncertainties. These statements are often, but are not always, made through the use of words or phrases such as “anticipates,” “intends,” “estimates,” “plans,” “expects,” “we believe,” “we intend,” and similar words or phrases, or future or conditional verbs such as “will,” “would,” “should,” “potential,” “could,” “may,” or similar expressions. Actual results may differ significantly from the expectations contained in the forward-looking statements. Among the factors that may result in differences are the inherent uncertainties associated with clinical trial and product development activities, regulatory approval requirements, competitive developments, and the availability of resources and the allocation of resources among different potential uses. These and other significant factors are discussed in greater detail in Aastrom’s Annual or Transition Report on Form 10-K or 10-K/T, Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. These forward-looking statements reflect management’s current views and Aastrom does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release except as required by law.