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EXHIBIT 99.4
EXHIBIT 99.4
Pathogen Inactivated Platelets (plt) Using Helinx™ Technology (INTERCEPT plt) Are Hemostatically Effective in Thrombocytopenic Patients (tcp pts): TheSPRINT Trial
Background: INTERCEPT plt (IP) are prepared with amotosalen HCl (S-59) & UVA light to inactivate a broad spectrum of pathogens & WBC in INTERCEPT platelet (plt) products (IP).SPRINT, a randomized double-blind controlled multi-center Phase III non-inferiority trial, compared the efficacy & safety of single donor plt (SDP) IP with untreated SDP (UP) in tcp pts requiring plt support.Methods: The 1° endpoint, the % of pts with clinically relevant bleeding (grade 2, WHO criteria) during a period of plt transfusion (txn) support, was assessed daily for 8 organ systems. Post txn bleeding & plt count increments (CI) for all on-protocol txn (2378 IP; 1799 UP) were compared by longitudinal regression analysis (LRA), with plt dose & other covariates.Results: Between 7/1999 & 1/2001, 671 pts were randomized at 12 US sites to receive up to 28 days of plt txn with IP or UP. 645 pts received>1 plt txn (ITT population). 280 (88%) IP and 294 (90%) UP pts completed the txn period. Age, race, gender, 1° diagnosis, and reason for plt txn support were similar between groups. 91% of IP & 95% UP txn were on-protocol. Mean days of storage was 3.4 for IP & 3.6 for UP.
|
|---|
Endpoints
| INTERCEPT (IP)
(n=318)
| Untreated (UP)
(n=327)
| P value
(95% CI of Diff)
|
|---|
| % Pts with grade 2 bleeding | 58 | 57 | 0.80
(-6.6%, 8.6%) |
|
| % Pts with grade 3 & 4 bleeding | 4 | 6 | 0.24
(-5.4%, 1.4%) |
|
| Pre-txn plt count (x109/L) | 15 | 15 | 0.88 |
|
| 1 Hr Post-txn plt count (x109/L) | 37 | 50 | <0.001 |
|
| 24 Hr Post-txn plt count (x109/L) | 28 | 36 | <0.001 |
|
| 1 Hr Corrected CI (CCI, × 103) | 11.1 | 16.0 | <0.001 |
|
| 24 Hr CCI (x 103) | 6.7 | 10.1 | <0.001 |
|
| Mean transfused plt dose (x 1011) | 3.7 | 4.0 | <0.001 |
|
| % Plt doses <3 × 1011 | 20 | 12 | <0.001 |
|
| Mean total dose plts (x 1011) | 29.4 | 24.1 | 0.01 |
|
| Mean no. plt txn (range) | 8.4 (1,49) | 6.2 (1,48) | <0.001 |
|
| Mean interval between plt txn (days) | 1.9 | 2.4 | <0.001 |
|
| Mean duration plt support (days) | 11.8 | 10.6 | 0.08 |
|
| % Plt txn with txn reactions | 3.0 | 4.4 | 0.02 |
|
| Mean no. RBC txn | 5.6 | 5.0 | 0.12 |
|
Mean days of grade 2 bleeding, adjusted for days of plt txn, was similar for IP & UP, 0.19 & 0.16, respectively (p=0.08). By LRA, comparable doses of IP & UP resulted in lower mean 1 & 24 hr CI for IP, by 10 & 6.6 × 109plt/L, respectively (p<0.001) but post-txn bleeding (> grade 2) was similar for IP & UP pts and independent of dose. 21% of IP & 7% of UP pts had 2 successive 1 hr CCI < 5 x 103 (p<0.001). These low CCI were transient (5.9% of IP & 8.7% of UP pts had 1 hr CCI persistently < 5 × 103 thru end of txn period) and not immune-mediated. LCA was positive in 16% of IP & 22% of UP pts; anti-plt antibody was present in 6% of IP & 9% of UP pts. No antibodies to S-59 neoantigens were detected.Conclusions: INTERCEPT platelets were as effective as conventional plt for prevention & treatment of bleeding in tcp pts requiring multiple plt txns. However IP resulted in lower CI & CCI, more IP txn & shorter txn intervals. LRA suggests increased doses of IP per txn can improve the CI. INTERCEPT platelets provide pathogen inactivation while maintaining hemostatic efficacy.
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EXHIBIT 99.4EXHIBIT 99.4
