Product seems effective for ITI in severe hemophilia A

Biogen Idec

Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.

Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.

Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.

In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.

No adverse events were reported in this study.

Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.

The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.

The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.

First-timer results

Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.

Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.

The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.

Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.

The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.

All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.

Rescue results

Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).

Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.

Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.

There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.

Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.

In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.

“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.

“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”

Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).

Biogen Idec

Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.

Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.

Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.

In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.

No adverse events were reported in this study.

Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.

The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.

The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.

First-timer results

Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.

Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.

The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.

Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.

The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.

All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.

Rescue results

Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).

Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.

Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.

There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.

Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.

In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.

“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.

“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”

Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).

Biogen Idec

Results of a retrospective study suggest a recombinant factor VIII Fc fusion protein (rFVIIIFc) can be effective for immune tolerance induction (ITI) in patients with severe hemophilia A and inhibitors.

Four of 7 first-time ITI patients achieved tolerization with rFVIIIFc at a median of 7.8 months.

Of 12 patients who had previously received treatment for ITI, 7 achieved a negative inhibitor level with rFVIIIFc. However, only 3 of these patients were still negative at the time of analysis.

In all, 16 of the 19 patients studied remained on rFVIIIFc for prophylaxis or ITI, and researchers said longer follow-up was needed.

No adverse events were reported in this study.

Manuel Carcao, MD, of The Hospital for Sick Children in Toronto, Ontario, Canada, and his colleagues conducted this study and published the results in Haemophilia.

The research was sponsored by Bioverativ Therapeutics, Inc. Bioverativ markets rFVIIIFc as Eloctate in some countries. Sobi markets rFVIIIFc (or efmoroctocog alfa) as Elocta in other countries.

The study included 19 patients—7 first-time ITI patients and 12 rescue patients—with severe hemophilia A and FVIII inhibitors.

First-timer results

Four of the 7 first-timers were tolerized and had transitioned to rFVIIIFc prophylaxis at the time of analysis.

Three patients met the definition of tolerization at 5 months, 7 months, and 9 months, respectively. All were all on a daily rFVIIIFc (85-200 IU/kg) regimen.

The fourth patient, who had been on a 3-times-per-week (50 IU/kg) ITI regimen, was considered tolerized at 14.8 months.

Of the 3 remaining patients, 2 had a decrease in Bethesda titer. The first patient had a decrease from 32 Bethesda units (BU) to 18 BU after 18 weeks of ITI. The second patient had a decrease from 378 BU to 23 BU after 58 weeks of ITI.

The third patient had an initial increase in titer from 3 BU to 16 BU after 15 weeks of rFVIIIFc. He went on to receive ITI with a different factor but did not respond. He resumed rFVIIIFc ITI after 27 weeks and had been receiving it for 7 weeks at the time of analysis. His most recent Bethesda titer had fallen. The researchers said this patient had been poorly compliant with ITI.

All 7 first-time ITI patients were still receiving rFVIIIFc—4 as prophylaxis and 3 for ITI—at the time of analysis.

Rescue results

Twelve patients had previously failed ITI. Seven of them achieved negative inhibitor levels with rFVIIIFc ITI. The median time to negativity was 14.1 weeks (range, 3 weeks to 67.6 weeks).

Three of the patients were still negative at the time of analysis. Two of them were still on rFVIIIFc ITI, and 1 was on rFVIIIFc prophylaxis.

Four patients who initially achieved negativity later developed a titer greater than 0.6 BU. Two of these patients were still on rFVIIIFc ITI at analysis, and 2 switched to other factors.

There were 5 patients who did not achieve negative inhibitor levels. One of these patients had a decrease in titer from 36 BU to 22 BU after 10 weeks. For the other 4 patients, titer was either unchanged or increased while on ITI.

Four of the 5 patients who did not achieve negative inhibitor levels remained on rFVIIIFc ITI at analysis, and 1 was placed on bypass therapy.

In total, 9 of the 12 rescue patients were still on rFVIIIFc at analysis—9 for ITI and 1 as prophylaxis.

“The development of inhibitors is a tremendous challenge and significant burden for people with severe hemophilia A, and the goal of treatment should be eradication of inhibitors,” said Maha Radhakrishnan, MD, of Bioverativ.

“The results of this analysis are encouraging and support the need for additional and ongoing scientific research on [rFVIIIFc ] in ITI to determine whether an Fc-based recombinant factor VIII therapy can rapidly tolerize patients with inhibitors.”

Bioverativ and Sobi have initiated 2 prospective studies designed to further evaluate the use of rFVIIIFc for ITI in patients with severe hemophilia A and inhibitors (NCT03093480 and NCT03103542).