Alnylam Pharmaceuticals

• Scholar Rock has appointed David L. Hallal as CEO, transitioning from his role as Chairman of the Board, as the company prepares for the global launch of apitegromab for spinal muscular atrophy. • The company has bolstered its leadership team with three key appointments: Akshay Vaishnaw as President of R&D, R. Keith Woods as Chief Operating Officer, and Vikas Sinha as Chief Financial Officer. • Apitegromab, a first-in-class muscle-targeted treatment for SMA, has received FDA priority review following successful Phase 3 trials, with potential approval and launch expected later this year.

• An FDA advisory committee voted 9-3 in favor of approving Alnylam's Onpattro (patisiran) for transthyretin amyloidosis cardiomyopathy (ATTR-CM), with a final decision expected by October 8th. • Despite FDA reviewers questioning the clinical significance of Onpattro's modest efficacy in the APOLLO-B trial, the panel was swayed by the drug's established safety profile and potential to address the underlying disease mechanism. • If approved, Onpattro would compete with Pfizer's Vyndamax/Vyndaqel (tafamidis), which generated $2.5 billion in sales last year, marking another milestone for RNA interference technology following its historic 2018 approval for ATTR polyneuropathy.

The FDA has approved Oxlumo (lumasiran), the first-ever treatment for primary hyperoxaluria type 1 (PH1), an ultra-rare genetic disorder that causes kidney damage through excessive oxalate production.

Moderna has filed patent infringement lawsuits against Pfizer/BioNTech in multiple countries, claiming their Comirnaty vaccine infringes on mRNA technology patents that Moderna pioneered and invested billions in developing.

• Alnylam's RNAi drug vutrisiran demonstrated a 28% reduction in all-cause mortality and recurrent cardiovascular events in ATTR cardiomyopathy patients, with efficacy increasing to 33% in patients not taking Pfizer's tafamidis. • The HELIOS-B trial showed vutrisiran's benefits increased over time, with a 36% reduction in the primary endpoint at 42 months, positioning the quarterly-administered injection as a potential new standard of care. • Vutrisiran, already approved as Amvuttra for ATTR polyneuropathy, could reach multibillion-dollar sales if approved for cardiomyopathy, though it faces competition from BridgeBio's acoramidis and AstraZeneca/Ionis' eplontersen.

• Regeneron has formed a consortium with AbbVie, Alnylam, AstraZeneca, Biogen, and Pfizer, with each company committing $10 million to accelerate sequencing of 500,000 UK Biobank genomes by end of 2019. • The project aims to identify new biological targets for drug development, particularly for neurological diseases like Alzheimer's and Parkinson's, where current failure rates exceed 90%. • Regeneron's automated sequencing capabilities through its Genetics Center have dramatically reduced processing time, potentially revolutionizing drug discovery by linking genetic data with health records from 500,000 volunteers. • After an exclusive access period for consortium members, all sequencing data and research findings will be made publicly available to the broader scientific community.

• Alnylam's zilebesiran, an RNAi therapy for hypertension, has been granted an Innovation Passport by the UK's MHRA to expedite NHS access. • Zilebesiran targets angiotensinogen (AGT) and is designed for infrequent dosing, potentially improving patient compliance compared to daily oral medications. • The drug is currently in a Phase 2 trial (KARDIA-1) with results expected early next year, evaluating its efficacy in adults with inadequately controlled hypertension. • If approved, zilebesiran could offer a new treatment option for the 15 million people in the UK with hypertension, many of whom are inadequately managed.

• BridgeBio's Attruby demonstrates strong early launch performance, showing a 42% reduction in combined hospitalization and death at 30 months for ATTR-CM patients. • The company positions Attruby competitively with a lower list price than competitors, while emphasizing its superior efficacy data and focused distribution strategy. • CEO Neil Kumar defends BridgeBio's hub-and-spoke model, highlighting efficient capital allocation and the potential for multiple successful drug developments.

• Alnylam anticipates FDA approval for vutrisiran to treat ATTR amyloidosis with cardiomyopathy by March 23, 2025, and aims for EU and Japan approvals later in the year. • A Phase 3 trial for nucresiran in ATTR amyloidosis with cardiomyopathy is set to begin in the first half of 2025, expanding Alnylam's focus on cardiac amyloidosis. • Alnylam's pipeline progresses with zilebesiran in hypertension, mivelsiran in Alzheimer's, and ALN-6400 in bleeding disorders, with key data readouts and trial initiations expected in 2025.

• The FDA is set to decide on Biogen and Eisai's Leqembi for monthly intravenous maintenance in early Alzheimer's disease, potentially improving patient convenience. • AstraZeneca and Daiichi Sankyo await a decision on Dato-DXd for metastatic HR-positive, HER2-negative breast cancer, offering a new antibody-drug conjugate approach. • Vertex's suzetrigine, a non-opioid analgesic for moderate-to-severe acute pain, anticipates FDA verdict, representing a novel drug class for pain management. • SpringWorks' mirdametinib is under priority review for neurofibromatosis type 1-associated plexiform neurofibromas, addressing a significant unmet need.