– Highly statistically significant result observed on primary endpoint with a Win Ratio of 1.8 (p<0.0001)
– 58% of ties in Finkelstein-Schoenfeld (F-S) primary analysis broken by all-cause mortality and frequency of cardiovascular-related hospitalization; statistical significance also achieved on an F-S test with those two parameters alone (p=0.0182)
– Clinically meaningful and consistent separation observed on all measures of mortality, morbidity, function, and quality of life
– On-treatment survival rate of 81% versus placebo survival rate of 74% (absolute risk reduction of 6.43%; relative risk reduction of 25%)
– Highly statistically significant relative risk reduction of 50% (p<0.0001) observed on frequency of cardiovascular-related hospitalization
– Highly statistically significant and clinically meaningful treatment benefit observed at 30 months on the secondary endpoints of NT-proBNP (p<0.0001), KCCQ (p<0.0001), and 6-minute walk distance (p<0.0001)
– In comparative exploratory post hoc analyses enabled by tafamidis drop-in, albeit at low patient numbers, acoramidis showed 42% greater increase in serum TTR levels and a 92% improvement in median NT-proBNP relative to placebo + tafamidis
– No safety signals of potential clinical concern identified
– Company intends to file a New Drug Application (NDA) with the U.S. Food and Drug Administration by end of 2023; late-breaker presentation has been accepted for annual meeting of the European Society of Cardiology
PALO ALTO, CA, USA I July 17, 2023 I BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), is a commercial-stage biopharmaceutical company focused on genetic diseases and cancers. Today, alongside the dedicated physicians and courageous patients who participated, the Company reports positive results from ATTRibute-CM, its Phase 3 study of acoramidis in transthyretin amyloid cardiomyopathy, or ATTR-CM. ATTRibute-CM was designed to study the efficacy and safety of acoramidis, an investigational, next-generation, orally-administered, highly potent, small molecule stabilizer of transthyretin (TTR). BridgeBio will host an investor call on July 17, 2023 at 8:00 am ET to discuss these results.
“The outstanding results of the ATTRibute-CM study provide new hope to patients living with transthyretin amyloid cardiomyopathy, or ATTR-CM”, said Dr. Daniel Judge, Professor of Medicine and Cardiology at the Medical University of South Carolina, and Co-Chair of the ATTRibute-CM Steering Committee. “The consistent and clinically meaningful benefits on survival, hospitalization, and additional measures of illness severity are truly remarkable.”
“ATTR-CM is an increasingly recognized cause of heart failure. The results from BridgeBio’s ATTRibute-CM trial are very exciting and bring much hope to amyloidosis patients and their loved ones,” said Muriel Finkel, President of Amyloidosis Support Groups, a non-profit organization dedicated to the support of amyloidosis patients and caregivers.
Key results from the clinical trial include:
- A highly statistically significant improvement in the primary endpoint (a hierarchical analysis prioritizing in order: all-cause mortality, then frequency of cardiovascular-related hospitalization, then change from baseline in NT-proBNP, then change from baseline in 6-minute walk distance) demonstrated by a Win Ratio of 1.8 (p<0.0001).
- An 81% on-treatment survival rate (versus a 74% survival rate on placebo), which begins to approach actuarial models of life expectancy absent ATTR-CM (85% in this population as has been documented). The absolute risk reduction was 6.43% and the relative risk reduction was 25%.
- A highly statistically significant relative risk reduction of 50% (p<0.0001) on frequency of cardiovascular-related hospitalization. The impact and marked magnitude of risk reduction was seen across all analytical methods employed.
- The Company consistently observed a statistically significant treatment effect at 30 months across additional measured markers of morbidity, quality of life, and function:
- Change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (p<0.0001)
- Change from baseline in Kansas City Cardiomyopathy Questionnaire (p<0.0001)
- Change from baseline in 6-minute walk distance (p<0.0001)
- No safety signals of potential clinical concern were identified.
A key objective in the rational drug design of acoramidis was to maximize TTR stabilization at clinically achieved blood concentrations. Several lines of evidence suggest that maximizing stabilization could lead to improved benefits for ATTR patients:
- Historical ATTR genotype/phenotype data and the disease-protective properties of trans-allelic, trans-suppressor variants relative to pathogenic variants in compound heterozygotes and the general, nonvariant population
- The outperformance of 80mg tafamidis vs 20mg tafamidis in the previously published ATTR-ACT trial
- Results from ATTR-polyneuropathy clinical trials
BridgeBio’s design strategy to maximize TTR stabilization by acoramidis was to phenocopy the hyper stabilizing molecular mechanism of the T119M trans-allelic, trans-suppressor rescue mutation. Prior preclinical and clinical studies have shown that acoramidis demonstrates approximately twice the stabilization of already-marketed stabilizers.
The allowance of tafamidis drop-in after at least 12 months in both the placebo and the acoramidis arms of the ATTRibute-CM trial provided the Company an opportunity to analyze, in an exploratory post hoc fashion and albeit at low patient numbers, differences in stabilizer performance as measured by serum TTR and NT-proBNP. The findings at 30 months were that:
- Acoramidis showed a 42% greater increase in serum TTR levels versus tafamidis
- Acoramidis showed a 92% improvement in median NT-proBNP relative to placebo + tafamidis
No comparison can be made as to the potential effectiveness or safety of acoramidis and tafamidis, given that these are exploratory analyses, and the study was not prospectively designed for a head-to-head comparison.
“Our heartfelt thanks go out to the patients, their caregivers, investigators, and study staff who have actively participated in ATTRibute-CM and continue to contribute to this pivotal research,” stated Jonathan Fox, M.D., Ph.D., President and Chief Medical Officer of BridgeBio Cardiorenal. “We are extremely encouraged by the robustly positive and consistent findings of the ATTRibute-CM study, which confirm our position that highly potent TTR stabilization has the potential to profoundly impact patients’ lives. We look forward to presenting the data to health authorities to bring acoramidis to patients as expeditiously as possible.”
The Company intends to submit its NDA to the US FDA before the end of 2023, with regulatory filings in additional markets to follow in 2024. This activity will occur in parallel with the prosecution of the remainder of the BridgeBio portfolio, which like acoramidis consists of medicines that target well-described diseases at their source. Acoramidis has intellectual property protection out to at least 2039.
Webcast Information
BridgeBio will host an investor call and simultaneous webcast to discuss the results from the Phase 3 ATTRibute-CM study of acoramidis in patients with ATTR-CM on July 17, 2023, at 8:00 am ET. A link to the webcast may be accessed from the event calendar page of BridgeBio’s website at https://investor.bridgebio.com/. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days following the event.
About BridgeBio Pharma, Inc.
BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test, and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
SOURCE: BridgeBio Pharma
Post Views: 577
– Highly statistically significant result observed on primary endpoint with a Win Ratio of 1.8 (p<0.0001)
– 58% of ties in Finkelstein-Schoenfeld (F-S) primary analysis broken by all-cause mortality and frequency of cardiovascular-related hospitalization; statistical significance also achieved on an F-S test with those two parameters alone (p=0.0182)
– Clinically meaningful and consistent separation observed on all measures of mortality, morbidity, function, and quality of life
– On-treatment survival rate of 81% versus placebo survival rate of 74% (absolute risk reduction of 6.43%; relative risk reduction of 25%)
– Highly statistically significant relative risk reduction of 50% (p<0.0001) observed on frequency of cardiovascular-related hospitalization
– Highly statistically significant and clinically meaningful treatment benefit observed at 30 months on the secondary endpoints of NT-proBNP (p<0.0001), KCCQ (p<0.0001), and 6-minute walk distance (p<0.0001)
– In comparative exploratory post hoc analyses enabled by tafamidis drop-in, albeit at low patient numbers, acoramidis showed 42% greater increase in serum TTR levels and a 92% improvement in median NT-proBNP relative to placebo + tafamidis
– No safety signals of potential clinical concern identified
– Company intends to file a New Drug Application (NDA) with the U.S. Food and Drug Administration by end of 2023; late-breaker presentation has been accepted for annual meeting of the European Society of Cardiology
PALO ALTO, CA, USA I July 17, 2023 I BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), is a commercial-stage biopharmaceutical company focused on genetic diseases and cancers. Today, alongside the dedicated physicians and courageous patients who participated, the Company reports positive results from ATTRibute-CM, its Phase 3 study of acoramidis in transthyretin amyloid cardiomyopathy, or ATTR-CM. ATTRibute-CM was designed to study the efficacy and safety of acoramidis, an investigational, next-generation, orally-administered, highly potent, small molecule stabilizer of transthyretin (TTR). BridgeBio will host an investor call on July 17, 2023 at 8:00 am ET to discuss these results.
“The outstanding results of the ATTRibute-CM study provide new hope to patients living with transthyretin amyloid cardiomyopathy, or ATTR-CM”, said Dr. Daniel Judge, Professor of Medicine and Cardiology at the Medical University of South Carolina, and Co-Chair of the ATTRibute-CM Steering Committee. “The consistent and clinically meaningful benefits on survival, hospitalization, and additional measures of illness severity are truly remarkable.”
“ATTR-CM is an increasingly recognized cause of heart failure. The results from BridgeBio’s ATTRibute-CM trial are very exciting and bring much hope to amyloidosis patients and their loved ones,” said Muriel Finkel, President of Amyloidosis Support Groups, a non-profit organization dedicated to the support of amyloidosis patients and caregivers.
Key results from the clinical trial include:
- A highly statistically significant improvement in the primary endpoint (a hierarchical analysis prioritizing in order: all-cause mortality, then frequency of cardiovascular-related hospitalization, then change from baseline in NT-proBNP, then change from baseline in 6-minute walk distance) demonstrated by a Win Ratio of 1.8 (p<0.0001).
- An 81% on-treatment survival rate (versus a 74% survival rate on placebo), which begins to approach actuarial models of life expectancy absent ATTR-CM (85% in this population as has been documented). The absolute risk reduction was 6.43% and the relative risk reduction was 25%.
- A highly statistically significant relative risk reduction of 50% (p<0.0001) on frequency of cardiovascular-related hospitalization. The impact and marked magnitude of risk reduction was seen across all analytical methods employed.
- The Company consistently observed a statistically significant treatment effect at 30 months across additional measured markers of morbidity, quality of life, and function:
- Change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (p<0.0001)
- Change from baseline in Kansas City Cardiomyopathy Questionnaire (p<0.0001)
- Change from baseline in 6-minute walk distance (p<0.0001)
- No safety signals of potential clinical concern were identified.
A key objective in the rational drug design of acoramidis was to maximize TTR stabilization at clinically achieved blood concentrations. Several lines of evidence suggest that maximizing stabilization could lead to improved benefits for ATTR patients:
- Historical ATTR genotype/phenotype data and the disease-protective properties of trans-allelic, trans-suppressor variants relative to pathogenic variants in compound heterozygotes and the general, nonvariant population
- The outperformance of 80mg tafamidis vs 20mg tafamidis in the previously published ATTR-ACT trial
- Results from ATTR-polyneuropathy clinical trials
BridgeBio’s design strategy to maximize TTR stabilization by acoramidis was to phenocopy the hyper stabilizing molecular mechanism of the T119M trans-allelic, trans-suppressor rescue mutation. Prior preclinical and clinical studies have shown that acoramidis demonstrates approximately twice the stabilization of already-marketed stabilizers.
The allowance of tafamidis drop-in after at least 12 months in both the placebo and the acoramidis arms of the ATTRibute-CM trial provided the Company an opportunity to analyze, in an exploratory post hoc fashion and albeit at low patient numbers, differences in stabilizer performance as measured by serum TTR and NT-proBNP. The findings at 30 months were that:
- Acoramidis showed a 42% greater increase in serum TTR levels versus tafamidis
- Acoramidis showed a 92% improvement in median NT-proBNP relative to placebo + tafamidis
No comparison can be made as to the potential effectiveness or safety of acoramidis and tafamidis, given that these are exploratory analyses, and the study was not prospectively designed for a head-to-head comparison.
“Our heartfelt thanks go out to the patients, their caregivers, investigators, and study staff who have actively participated in ATTRibute-CM and continue to contribute to this pivotal research,” stated Jonathan Fox, M.D., Ph.D., President and Chief Medical Officer of BridgeBio Cardiorenal. “We are extremely encouraged by the robustly positive and consistent findings of the ATTRibute-CM study, which confirm our position that highly potent TTR stabilization has the potential to profoundly impact patients’ lives. We look forward to presenting the data to health authorities to bring acoramidis to patients as expeditiously as possible.”
The Company intends to submit its NDA to the US FDA before the end of 2023, with regulatory filings in additional markets to follow in 2024. This activity will occur in parallel with the prosecution of the remainder of the BridgeBio portfolio, which like acoramidis consists of medicines that target well-described diseases at their source. Acoramidis has intellectual property protection out to at least 2039.
Webcast Information
BridgeBio will host an investor call and simultaneous webcast to discuss the results from the Phase 3 ATTRibute-CM study of acoramidis in patients with ATTR-CM on July 17, 2023, at 8:00 am ET. A link to the webcast may be accessed from the event calendar page of BridgeBio’s website at https://investor.bridgebio.com/. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days following the event.
About BridgeBio Pharma, Inc.
BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test, and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
SOURCE: BridgeBio Pharma
Post Views: 577
