A BridgeBio Pharma drug touted by the company may be better than an approved Pfizer product in addressing the protein at the root of rare heart disease lose Beat the placebo in the first part of a key clinical trial. BridgeBio called the results “confusing” and executives had more questions than answers, but they still had hopes for experimental treatments, and pointed out that the second part of the phase 3 clinical trial-is not expected to release data for another year Or longer.
BridgeBio’s drug acoramidis is being developed to treat transthyretin amyloidosis, a rare and life-threatening disease that can thicken the heart muscle, hinder its function, and may lead to heart failure. ATTR can be inherited, but in people without genetic mutations, the disease can still develop as a normal part of aging.
A total of 632 participants representing the two forms of ATTR participated in the placebo-controlled phase 3 clinical trial. The main goal of the first part of the study is to show improvement after 12 months of treatment based on a test that assesses how far patients can go in 6 minutes. The performance of this test decreases with age. In healthy elderly people, the typical decline is only 7 meters in 12 months.
According to preliminary results released on Monday by BridgeBio, headquartered in Palo Alto, California, the average drop in patients treated with acoramidis was 9.28 meters—compared to the average drop of 7.04 meters in the placebo group, not enough to show statistics Significant difference.in a Investor introductionBridgeBio stated that the placebo group in the study was “significantly better” than the historical control, and its decline was more closely related to the decline normally observed in healthy elderly people. In addition, in the key study of Pfizer’s ATTR drug, the placebo group studied by BridgeBio outperformed the placebo group by more than 70%. Vyndaqel, approved in 2019According to Pfizer’s financial statements, by 2020, revenue from the drug and the second preparation called Vyndamax will be close to 1.3 billion U.S. dollars.
In Monday’s announcement, BridgeBio CEO Neil Kumar called the results of acoramidis “disappointing and inexplicable.” BridgeBio pointed out in the investor introduction that the Phase 3 test of the enrolled patients is similar to the enrolled patients in the key Vyndaqel study. According to the company, current assumptions about surprising placebo results are background biases, training biases, and the evolution of methods of diagnosing and treating ATTR.
When a protein called transthyretin misfolds, ATTR occurs, resulting in an unstable form that causes amyloid to deposit on nerves and organs (including the heart). According to BridgeBio, it is estimated to affect more than 400,000 people worldwide. In 2018, the FDA approved Alnylam Pharmaceuticals’ drug Onpattro as a treatment for genetic ATTR that affects nerves. Onpattro uses RNA interference to “silence” genes that produce proteins at the root of the disease. Later that year, the FDA Tegsedi, A drug developed by Akcea Therapeutics and Ionis Pharmaceuticals to treat nerve pain caused by inherited ATTR. The drug is an antisense oligonucleotide designed to bind transthyretin and degrade it.
Although Pfizer’s Vyndaqel was the first drug approved for the treatment of ATTR that affects the heart, BridgeBio’s claim is that the drug is more effective. Acoramidis is a small molecule designed to bind to transthyretin and stabilize it, thereby reducing the level of amyloid formation, which may slow down or even prevent the progression of the disease. Pfizer’s Vyndaqel is also a transthyretin stabilizer, but BridgeBio describes its drug as a better stabilizer.During the company’s October R&D day, executives pointed out Laboratory test results It shows that the lower dose of acoramidis is better than any of Pfizer’s drugs, achieving “almost complete stability” of transthyretin.
Although it failed to achieve the main objectives of the Phase 3 study, BridgeBio pointed out that its drugs showed improvements based on questionnaires measuring quality of life, cardiac biomarkers, and tests that measure the concentration of transthyretin in the blood. The drug was also well tolerated by patients in clinical trials without any signs of safety issues. For these reasons, the independent data monitoring committee that evaluated the progress of the phase 3 clinical trial recommended that the acoramidis study be continued. The clinical trial was designed as a 30-month study, and BridgeBio stated that the committee and the company agreed that acoramidis has the potential to show patient benefit at that time. In addition to further evaluating the changes in the six-minute walk test, the 30th month goal also includes two indicators: the frequency of hospitalizations for cardiovascular causes and the number of deaths from all causes.
“This drug appears to be pharmacologically positive And it’s well tolerated, we have observed an improvement in the quality of life, and the trend of adverse events leading to death is promising,” Kumar said. “This drug seems to be doing what we want. If we observe enough clinical outcome events in the 30th month, I still hope that we can demonstrate the benefits of acoramidis treatment. “
Acoramidis is the main product candidate of Eidos Therapeutics. Eidos Therapeutics is a spin-off company from BridgeBio and becomes a Publicly traded The company was established in 2018, although its former parent company retained a majority stake.Nearly a year ago, BridgeBio completed its get The Eidos shares that it does not own allow it to control the ATTR plan.
BridgeBio stated that the Phase 3 study of acoramidis has been completed and fully funded. The company’s cash reserves currently total US$800 million; if other assets reach key targets in the coming year, an additional US$300 million milestone payment may be made. BridgeBio expects that the other four clinical phases of the project may release key data in the coming year. However, preliminary data for the second part of the acoramidis phase 3 study is not expected to be available until 2023.
The disappointing data released on Monday hit BridgeBio’s share price, which fell to $11.61 per share in midday trading, down more than 71% from Friday’s closing price.
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