Alnylam is awarded FDA approval for treatment of polyneuropathy of hATTR amyloidosis with Amvuttra

The once narrow scope of amyloidosis treatment is continuing to expand,as Alnylam Pharmaceuticals has been granted FDA approval for their gene silencing product, AMVUTTRA, a key treatment option for polyneuropathy associated with hereditary transthyretin amyloidosis (hATTR). After the final market preparation steps have been taken, AMVUTTRA will be made available for treatment, as data received from secondary endpoint results in the HELIOS-A Phase III study were positively reviewed by the U.S. Food and Drug Administration. The FDA was satisfied with the trial’s overall results in neuropathy impairment improvement, quality of life, functional status and patient performance. 


Unlike other currently approved infusion based gene-silencing agents, Amvuttra is administered subcutaneously, once every three months, thus inhibiting the production of transthyretin protein in the liver. In the mean time, Amvuttra is further being investigated in the ELIOS-B study, to determine which benefits it may bring to patients with cardiac ATTR amyloidosis. 


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Positive results for CAEL-101 in patients with AL-Amyloidosis

Research currently underway, to evaluate the monoclonal antibody CAEL-101, as a form of treatment for AL-Amyloidosis, is heading in a positive direction. The results of this phase 1, open label, dose escalation trial, are unfolding in such a way that may in future enable CAEL-101 to be considered for therapeutic purposes.

AL-Amyloidosis is characterized by aggregates of misfolded, insoluble proteins, which may deposit in select organs, interfering with the organ’s function. Typically, the heart is the most affected. Once organ deposition occurs, the purpose of CAEL-101 monoclonal antibody is to attach to the abnormal protein and spark phagocytosis. Thereafter, the interfering protein is removed from the affected organ(s) and, proper organ function can be restored.


In order to assess the efficacy of CAEL-101, the trial focused on AL-Amyloidosis patients who previously had neither shown limited cardiac, renal or hepatic function, nor suffered from uncontrolled infection or other co-morbidites. In phase 1a of the study, a single dose of CAEL-101 was administered to 8 patients. Each subsequent patient received a somewhat higher dose of the antibody unless toxicity had previously been noted. This phase was followed by a second part of the study, in which patients were given 4 infusions, which also increased in dose until a maximum dose was achieved. In phase Ib, no dose limiting toxicities were reported as the dose was increased to a maximum of 500 mg/m2. Determining the maximum tolerated dose was one of the trial’s underlying objectives.  Subsequently, overall tolerance, safety, pharmacokinetics and possible clinical benefits were also being evaluated.



The results of this phase 1a/b trial confirmed that CAEL-101 was well tolerated and contributed to a positive organ response in 24 patients who had experienced organ involvement. Additionally, a therapeutic response to CAEL-101 was seen in 63% of these patients with no drug-related fatalities being reported. 


The entire article can be found under the following link:



Eplontersen is granted Orphan Drug  designation

Eplontersen, a ligand-conjugated antisense (LICA) medicine, has, to date, not only been tested in phase III of its clinical trial, but has recently also been granted Orphan Drug Designation (ODD) in the US by the Food and Drug Administration (FDA).  


The aim of the Phase III Eplontersen clinical trial is to treat amyloid transthyretin cardiomyopathy and amyloid transthyretin polyneuropathy in both hereditary and non-hereditary forms of TTR amyloidosis (ATTR). The treatment is based on the involvement of a ligand molecule targeted at receptors on cell surfaces in a specific manner so as to suppress and furthermore to reduce the production of transthyretin in patients with transthyretin-mediated amyloidosis (ATTR). If this protein remains untreated both progressive heart failure in the form of amyloid transthyretin cardiomyopathy (ATTR-CM) and motor disability through the polyneuropathy are anticipated.


Orphan Drug Designation is granted to medicines and potential new therapies by the FDA whose intention it is to diagnose, treat and prevent rare diseases or disorders.  Hence, new hope is being seen in Eplontersen for a patient population whose treatment resources remain limited. 


The entire article can be found under the following link:

Alnylam Presents Positive HELIOS-A

Study Results of Investigational Vutrisiran

On the 21st of January 2022, the leading RNAí therapeutics company Alnylan Pharmaceuticals, Inc. published findings that at 18 months into the HELIOS-A Phase 3 study, all secondary endpoints had been met. In this global, randomized, open-label study, Alnylan Pharmaceuticals, Inc. is evaluating the safety and efficacy of Vutrisiran, a subcutaneously administered RNAi therapeutic, currently being investigated in the treatment of hATTR Amyloidosis.


Once administered, Vutrisiran targets specific messenger RNA sequences involved in the production of wild-type and variant transthyretin (TTR) protein. These RNA sequences are then silenced, further blocking the transthyretin protein synthesis pathway, which otherwise would lead to abnormal amyloid production, accumulation and unwanted organ deposition, commonly associated with hAATR Amyloidosis.


Amongst HELIOS-A trial participants, Vutrisiran was shown to meet all secondary endpoints relating to polyneuropathy as compared to those receiving placebo. These endpoints included the evaluation of statistical improvement in neuropathy impairment, overall quality of life (QoL), gait speed, nutritional status and overall disability in both groups. Having previously met the primary endpoints at month 9, Alnylam’s HELIOS-A early findings had already been presented at the American Academy of Neurology in 2021 during their virtual annual meeting.


Further to the polyneuropathy findings, overall improvements in exploratory cardiac endpoints such as NT-proBNP (a biomarker of cardiac stress) and echocardiography parameters were also found in trial patients receiving Vutrisiran.


In light of these results, both the U.S. and the European Union have granted Vutrisiran an orphan drug designation status for the treatment of ATTR Amyloidosis, enabling a further step in its implementation for patients with this rare disease. Currently, the therapeutic remains under review by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Brazilian Health Regulatory Agency (ANVISA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). 


To read the entire article go to the following link:

BridgeBio/Eidos Phase III Clinical Trial Update

The BridgeBio/Eidos Study Team is excited to share an important update regarding ATTRibute-CM, the Phase 3 clinical trial evaluating the efficacy and safety of acoramidis (AG10) in individuals diagnosed with cardiomyopathy associated with transthyretin amyloidosis (NCT03860935). 


This week, the last patient enrolled in ATTRibute-CM completed their 12 month visit. The achievement of this important milestone means that Part A of the ATTRibute-CM is now complete!


Thank you for championing the ATTR patient voice, providing insight and guidance to the BridgeBio/Eidos team and educating patients on the importance of clinical trials, including ATTRibute-CM. It is with your support that we were able to achieve this milestone.


When to Expect ATTRibute-CM Part A Topline Results

In late December 2021, BridgeBio/Eidos plans to share the Part A top-line results for the primary endpoint (change from baseline in 6MWD), the key secondary endpoint (change from baseline in KCCQ overall score) and an overall assessment of safety and tolerability. Additional results will be communicated in greater detail at academic conferences in 2022 and in a series of scientific papers submitted for publication in the peer-reviewed literature.  Summaries, updates and more information will be sent as data is released.


Important Note Regarding ATTRibute-CM Part B

While the Part A results may be encouraging, the Part B readout on all-cause mortality and the frequency of CV-related hospitalisation is critical to evaluating the overall efficacy of acoramidis in treating ATTR-CM, as well as informing further on the long-term safety of this investigational drug. As such, participants who completed Part A will continue their current trial regimen through Part B, an additional 18 months. Those who complete Part B will have been part of the study for a total of 30 months. 


All eligible participants who complete the full 30 months of ATTRibute-CM will be invited to receive acoramidis as part of the open-label extension protocol (NCT04988386).


The BridgeBio/Eidis team is very proud of the work that was accomplished together in the last two years, and is particularly grateful considering the context of the ongoing COVID pandemic. Their gratitude goes to all those who have contributed to this important program: trial participants, their families, investigators, support staff and you.

Recommendations for the treatment of Transthyretin Amyloidosis with Tafamidis

According to ESC 2021 guidelines, Tafamidis is recommended in patients with genetic testing proven hereditary hTTR-CMP and NYHA class I or II symptoms to reduce symptoms, CV hospitalization and mortality.

Tafamidis  is recommended in patients with wtTTR-CA and NYHA class I or II symptoms to reduce symptoms, CV hospitalization and mortality.

Vutrisiran receives Fast Track Designation from FDA

Alnylam has submitted a new drug application (NDA) to the FDA for vutrisiran, which could bring another treatment option to patients with ATTR amyloidosis. Vutrisiran received “Fast Track” Designation, which is a process designed to expedite the review of drugs to treat serious medical conditions and fill an unmet medical need, with the goal of getting new drugs to patients sooner. Both the NDA and fast track designation are encouraging signs for vutrisiran’s future in the TTR amyloidosis space.


Vutrisiran is an investigational RNAi therapeutic being studied in both hereditary and wild-type transthyretin amyloidosis patients (hATTR and ATTRwt). HELIOS-A is the name of the study that is investigating vutrisiran for patients with hATTR with polyneuropathy. Vutrisiran is a subcutaneous injection given every 3 months which, if approved, will offer patients another treatment option in addition to the two currently approved for use in hATTR; Onpattro® and Tegsedi®. Like these treatments, vutrisiran is also classified as a gene-silencer, and aims to inhibit production of the transthyretin (TTR) protein in the liver, thereby reducing the levels of TTR in the body, preventing amyloid build-up and organ damage.


Alnylam presented positive results from HELIOS-A at the American Academy of Neurology meeting last month. The phase 3 study met both its primary and secondary endpoints, or study outcomes, at the 9-month mark. The HELIOS-A study enrolled 164 patients with hATTR polyneuropathy, randomizing 3:1 to receive either vutrisiran every three months or patisiran every 3 weeks for 18 months. The primary endpoint was the change from baseline in the modified Neuropathy Impairment Score (mNIS+7) at 9 months as compared to placebo data. This study used placebo data from the Phase 3 study of patisiran, called APOLLO, which took place a few years ago and led to the approval of Onpattro® (patisiran) in 2018. The two secondary endpoints were changes in quality of life assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and walking speed assessed by the timed 10-meter walk test (10-MWT), also compared to the historical placebo data.


Vutrisiran showed significant improvements in neuropathy scores, quality of life, and walking speed in the HELIOS-A study, compared to the placebo arm of the historical APOLLO study. Additionally, more than half of patients who received vutrisiran in HELIOS-A showed an improvement of polyneuropathy manifestations. Vutrisiran was also shown to have an encouraging safety profile. The study will continue for its fully planned 18 months, but the data shared at the 9 month point holds promise.


After sharing the positive results last month, Alnylam filed a new drug application (NDA) for vutrisiran with the United States FDA. Any new drug approved for sale and marketing in the US must complete an NDA. The goals of the NDA are to provide enough information for the FDA to reach decisions on whether the drug is safe and effective. To read more about the full Drug Approval Process with the US FDA, view the infographic here.


Vutrisiran also received “Fast Track” Designation, which is a process designed to expedite the review of drugs to treat serious medical conditions and fill an unmet medical need, with the goal of getting new drugs to patients sooner. Since treatments for hATTR with polyneuropathy are already approved, to receive fast track, vutrisiran would need to have shown some advantage over the available therapies, such as superior effectiveness, less serious side effects, or improved patient outcomes.


The fully planed 18-month results of HELIOS-A are expected in late 2021 and FDA review and decision on approving the new therapy expected in early 2022. To read the full press release from Alnylam, click here.


Vutrisiran is also being studied in patients with cardiac ATTR amyloidosis. The study which is ongoing is called HELIOS-B and is investigating vutrisiran for ATTR patients with cardiomyopathy (both hereditary and wild-type). HELIOS-B is still recruiting, and results are not expected for a couple of years.


If you are interested in being kept informed about clinical trials that you may be a match for, make sure you sign up for MyAmyloidosisPathfinder, and keep your profile up to date! We’ll let you know if you may be eligible for a clinical trial.