---
title: "Alnylam’s Next Test: Winning the First Prescription"
url: https://drugnews.com.tw/articles/2026-10-16-attr-rnai-first-prescription-en.html
date: 2026-10-16
lang: en
category: "商業分析系列"
tags: ["RNA therapeutics","Alnylam","BridgeBio","ATTR cardiomyopathy","Amvuttra","Attruby"]
summary: "Amvuttra sold $1 billion in a quarter, yet Alnylam cut its full-year TTR revenue forecast as the initial wave of patients switching treatment was largely exhausted. BridgeBio is using medical-record evidence to win new patients from Pfizer’s tafamidis. In the ATTR heart-drug battle, the first prescription decides who wins."
json: https://drugnews.com.tw/articles/2026-10-16-attr-rnai-first-prescription-en.json
publisher: Drugnews｜藥時事 (https://drugnews.com.tw/)
---
$1.012 billion. That was the global revenue from Alnylam’s RNA heart drug Amvuttra in the second quarter of this year.

Just over a year after gaining its cardiomyopathy indication, it is already Alnylam’s biggest product. Yet in the same earnings report, the company cut its full-year TTR product revenue forecast from $4.4–4.7 billion to $4.2–4.5 billion.

The reason is practical: many of the U.S. patients who had waited a long time for a new drug have now made the switch.

On October 11, rival BridgeBio released another U.S. medical-record study. Patients newly starting its oral drug Attruby had an 18% lower risk of deterioration events, including death and hospitalization, than patients newly starting Pfizer’s established drug tafamidis.

Our view: this heart-drug battle has moved from “whose drug is newer” to “who wins a new patient’s first prescription.” Oral drugs are already at the door. To sustain rapid growth, Alnylam needs to show why its drug deserves to be used first.

## 01｜One Disease, Three Companies, Three Approaches

The disease is called ATTR cardiomyopathy. TTR protein made in the liver breaks apart and accumulates in the heart, gradually making it stiff and causing it to fail.

The three companies intervene at different points:

| | Pfizer’s tafamidis | BridgeBio’s Attruby | Alnylam’s Amvuttra |
|---|---|---|---|
| Approach | Holds TTR protein together so it does not break apart | Also a stabilizer, with a pitch of more complete stabilization | Uses RNA interference to make the liver produce less TTR |
| Administration | Oral | Oral, twice daily | One injection every three months, administered by a healthcare professional |
| U.S. cardiomyopathy approval | 2019; first to market | November 2024 | March 2025 |
| Latest results | — | $222.4 million in second-quarter U.S. revenue | $1.012 billion in second-quarter global revenue |

Pfizer was this market’s first dominant player. BridgeBio is challenging it with another oral stabilizer. Alnylam has taken an entirely different route: rather than holding the protein together, it reduces how much is made in the first place.

![Figure 1｜RNA silencing and oral stabilizers intervene at different points in the TTR disease process](https://drugnews.com.tw/assets/articles/attr-rnai-first-prescription-en/figure-01.png)
*Figure 1｜Amvuttra makes the liver produce less TTR; Attruby stabilizes the TTR tetramer. The two drugs act at different points in the disease process.*

## 02｜Alnylam’s First Wave Came After Other Treatments Fell Short

Part of Amvuttra’s rapid early growth came from demand already waiting for it.

Many patients had taken stabilizers but continued to deteriorate, leaving them waiting for a new drug. When Amvuttra launched, this pool of patients accumulated over years came in at once. Alnylam was clear in its earnings report: once this “pent-up demand” had been released, U.S. second-line growth returned to a normal pace.

That is why the forecast came down. In other words, a substantial part of Alnylam’s earlier growth came from taking over patients whose previous treatment had not kept their disease under control.

That route has a ceiling. If newly diagnosed patients all receive an oral drug as their first prescription, an RNA drug can only wait to take over those who deteriorate.

## 03｜BridgeBio Goes After Pfizer’s Patients Before Taking On RNA Drugs

BridgeBio’s calculation is shrewder: it is in no rush to persuade doctors to change the route of administration. Instead, it wants doctors who have already decided on an oral drug to choose its product over Pfizer’s.

The October 11 study was built for that purpose. Using the U.S. Epic medical-record database, it compared 910 Attruby users with 1,774 tafamidis users after matching. Across a composite of four events—death, hospitalization, new-onset atrial fibrillation and intensified diuretic treatment—the Attruby group had an 18% lower risk, with a hazard ratio of 0.82.

A separate insurance-claims study published in September pointed in the same direction.

This was a retrospective medical-record study, not a randomized trial. For death alone, the difference between the groups was not statistically significant. But for doctors deciding which oral drug to prescribe first, this evidence is already useful to consider.

BridgeBio also said in its second-quarter earnings report that Attruby’s growth came mainly from new patients who had not previously been treated. The first prescription is exactly what it wants.

![Figure 2｜Both companies seek treatment-naïve patients, but their new evidence answers different questions](https://drugnews.com.tw/assets/articles/attr-rnai-first-prescription-en/figure-02.png)
*Figure 2｜BridgeBio’s new study uses tafamidis as the comparator; Alnylam’s analysis looks at adding vutrisiran on top of tafamidis. The two datasets answer different questions.*

## 04｜Alnylam’s Countermove: Add On Instead of Displace

Alnylam sees this too. Its answer is to add its drug on top of oral treatment rather than replace it.

On August 30, Alnylam published an analysis of the HELIOS-B trial in JACC. Of the 654 patients, 259 were already taking tafamidis at baseline. With Amvuttra added, the rate ratio for death and recurrent cardiovascular events in this group was 0.79; in the group not taking tafamidis, it was 0.67.

The direction of effect was consistent across the two groups, giving researchers a reason to study “oral drug plus RNA drug.” But this subgroup analysis was not designed to establish the case for add-on treatment. Dedicated trials are still needed before doctors can make it routine.

That is Alnylam’s biggest open question today. If it can establish the evidence for adding treatment, it can reach patients taking oral drugs without having to win the first prescription. If it cannot, it will have to compete head-on for new patients.

![Figure 3｜After launch, both companies continue to build evidence on treatment sequencing](https://drugnews.com.tw/assets/articles/attr-rnai-first-prescription-en/figure-03.png)
*Figure 3｜The two mechanisms reached the market in succession in 2024–2025. The new data in 2026 help answer “which comes first?” and “should another drug be added?”*

## 05｜Read the Earnings Reports for Where Patients Come From

The two companies’ revenue figures cannot be used directly to calculate market share. Amvuttra’s $1.012 billion covers global sales across indications; Attruby’s $222.4 million covers the U.S. alone.

What matters is the source of growth. At Alnylam’s next earnings report, a question worth asking is how much comes from newly diagnosed patients receiving their first treatment. For BridgeBio, watch whether growth in new patients can continue, and whether longer follow-up in the medical-record study makes the mortality difference clearer.

![Figure 4｜The composite endpoint and death alone must be read separately within the same medical-record study](https://drugnews.com.tw/assets/articles/attr-rnai-first-prescription-en/figure-04.png)
*Figure 4｜BridgeBio’s matched study of 2,684 patients, announced on October 11: the hazard ratio for the four-event composite was 0.82; for death alone, it was 0.85, with a confidence interval crossing 1.*

## Conclusion｜The Next Revenue Starts With the First Prescription

All three companies have cleared the hurdle of reaching the market. The contest now is which drug comes to a doctor’s mind first when a new patient arrives.

BridgeBio is using medical-record data to take Pfizer’s place. Alnylam is using add-on evidence to find a way around that contest. Watch three things next: the share of new patients at Alnylam, the full paper from BridgeBio’s study, and whether anyone starts a dedicated trial of “oral drug plus RNA drug.” Whoever wins the first prescription wins this market’s next billion.

*This article is an industry and company analysis and does not constitute investment or medical advice.*

## References

1. BridgeBio／Acoramidis Associated with Significantly Improved Clinical Outcomes Versus Tafamidis in ATTR-CM in an Independent, Real-World Study of U.S. Electronic Health Records／2026-10-11／https://investor.bridgebio.com/news/news-details/2026/Acoramidis-Associated-with-Significantly-Improved-Clinical-Outcomes-Versus-Tafamidis-in-ATTR-CM-in-an-Independent-Real-World-Study-of-U-S--Electronic-Health-Records/default.aspx
2. Alnylam／Alnylam Pharmaceuticals Reports Second Quarter 2026 Financial Results and Highlights Recent Period Progress／2026-07-30／https://investors.alnylam.com/press-release?id=ddc78e15-7847-4066-8fdb-3562023a60f4
3. FDA／AMVUTTRA Prescribing Information／Revised March 2025／https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215515s006lbl.pdf
4. FDA／ATTRUBY Prescribing Information／Revised November 2024／https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216540s000lbl.pdf
5. Wright et al., Cardiology and Therapy／Comparative Effectiveness of TTR Stabilizers for the Treatment of ATTR-CM Using Real-World Evidence／2026-09-23／https://link.springer.com/article/10.1007/s40119-026-00476-2
6. BridgeBio／BridgeBio Reports Second Quarter 2026 Financial Results and Corporate Updates／2026-08-10／https://investor.bridgebio.com/news/news-details/2026/BridgeBio-Reports-Second-Quarter-2026-Financial-Results-and-Corporate-Updates/default.aspx
7. Hamatani et al., JACC／Effect of Vutrisiran According to Baseline Tafamidis Use in Transthyretin Amyloidosis With Cardiomyopathy: Insights From HELIOS-B／Published online August 30, 2026／https://www.jacc.org/doi/10.1016/j.jacc.2026.07.022
8. Alnylam／Alnylam Presents New Data at ESC Congress 2026 Reinforcing Strength in RNAi-Powered TTR Silencing Across ATTR-CM Patient Populations and Treatment Settings／2026-08-30／https://investors.alnylam.com/press-release?id=9c44884f-61bb-4f2e-85d5-09f4659cfc7c
9. FDA／Drug Trials Snapshot: ATTRUBY／Approved November 22, 2024／https://www.fda.gov/drugs/drug-trials-snapshots/drug-trials-snapshot-attruby
10. FDA／Search Orphan Drug Designations and Approvals: vutrisiran／Approved March 20, 2025／https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=637618
11. Pfizer／VYNDAQEL and VYNDAMAX Prescribing Information／Revised October 2023／https://labeling.pfizer.com/ShowLabeling.aspx?id=11685