Breaking News
April 25, 2019 - The Current issue of “The view from here” is concerned with Partnerships and Alliances
April 25, 2019 - Imaging method reveals long-lived patterns in cells of the eye
April 25, 2019 - Podcast: KHN’s ‘What The Health?’ The Abortion Wars Rage On
April 25, 2019 - Prolonged exposure therapy is more effective in treating veterans with PTSD, alcohol use disorder
April 24, 2019 - Our artificial cornea breakthrough could lead to self-assembling organs
April 24, 2019 - A Stanford black, female, gay surgery resident speaks out
April 24, 2019 - Donna Lynne on Extreme Sports, Lessons From the '60s, and Taking CUIMC to the Next Level
April 24, 2019 - Pain Clinics’ Doctors Needlessly Tested Hundreds Of Urine Samples, Court Records Show
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
April 24, 2019 - Versatile drug may protect baby from hazards of intraamniotic infections
April 24, 2019 - Financial transparency may diminish trust in doctors, new study finds
April 24, 2019 - Calling all Riders: Velocity Extends Free Registration 
April 24, 2019 - The Homeless Are Dying In Record Numbers On The Streets Of L.A.
April 24, 2019 - Blocking BRAF ubiquitination may be an effective treatment approach in melanoma
April 24, 2019 - Simple mobility test helps predict hospital readmission in elderly heart attack patients
April 24, 2019 - Novel fluorescence imaging system helps surgeons remove small ovarian tumors
April 24, 2019 - Uncovering the Structure of HIV Integrase to Inform Drug Discovery
April 24, 2019 - Medical Marijuana Use Rising Among Cancer Patients
April 24, 2019 - Artificial intelligence approach optimizes embryo selection for IVF
April 24, 2019 - Doctor or detective? Sleuthing mysteries in medical school
April 24, 2019 - CUIMC Community Gives Blood During Spring 2019 Columbia University Blood Drive
April 24, 2019 - Americans Overwhelmingly Want Federal Protections Against Surprise Medical Bills
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Ambiguous genitalia in newborns may be more common than previously thought
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
April 24, 2019 - New study provides better understanding on safety of deworming programs
April 24, 2019 - EEG used to detect impact of maternal stress on neurodevelopment in 2-month-old infants
April 24, 2019 - FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose
April 24, 2019 - A new way of finding compounds that prevent aging
April 24, 2019 - Mechanical training makes synthetic hydrogels perform more like muscle
April 24, 2019 - Study provides new insights into regulatory T cells’ role in protecting against autoimmune disease
April 24, 2019 - Pregnant women with type 1 diabetes are at greater risk of preterm birth
April 24, 2019 - ‘Tummy tuck’ can be safely performed in obese patients with no increase in complications
April 23, 2019 - ‘First’ 3-D print of heart with human tissue, vessels unveiled
April 23, 2019 - Which blood-based method works best to detect TB?
April 23, 2019 - Gene therapy cures infants suffering from ‘bubble boy’ immune disease
April 23, 2019 - Chemical-sampling wristbands detect similar exposures across three continents
April 23, 2019 - Management of Residual Limb Pain
April 23, 2019 - Molecular clock influences immune cell responses
April 23, 2019 - On the importance of culture, partnerships and diversity at the Dean’s Lecture Series
April 23, 2019 - Siddhartha Mukherjee Receives Lewis Thomas Prize for Writing About Science
April 23, 2019 - Dengue mosquito poses greatest danger of spreading Zika virus in Australia
April 23, 2019 - Scientists identify 104 high-risk genes for schizophrenia
April 23, 2019 - Abdominal etching can help patients to get classic ‘six-pack abs’ physique
Alnylam reports further progress on broadening the therapeutic potential of RNAi

Alnylam reports further progress on broadening the therapeutic potential of RNAi

image_pdfDownload PDFimage_print

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today further progress on the Company’s platform efforts in extrahepatic delivery of novel siRNA conjugates, including central nervous system (CNS) and ocular delivery in rat and non-human primates (NHPs). Preclinical results were presented at the Oligonucleotide Therapeutics Society (OTS) 2018 Annual Meeting held September 30 to October 3 in Seattle, WA.

“We are pleased to report on our continued progress on broadening the therapeutic potential of RNAi by demonstrating successful delivery to extrahepatic tissues such as the CNS and eye. The in vivo activity of our novel CNS and ocular siRNA conjugates is consistent across species and targets with potent and highly durable mRNA silencing. As we have seen with liver target gene silencing, we anticipate a highly competitive profile for our siRNA conjugates with increased potency, extended duration of action, and encouraging safety margins,” said Kevin Fitzgerald, Ph.D., Senior Vice President, Research at Alnylam. “We are excited to grow the potential universe of tissues, targets, and diseases addressable by RNAi therapeutics, expanding our efforts to reach patients in need of new therapies. We believe that the demonstration of potent, safe, and infrequent dosing may allow us to develop innovative RNAi therapeutics directed to these new targets.”

In NHP studies, a single intrathecal (IT) injection of a siRNA conjugate targeting the ubiquitously expressed β-catenin mRNA transcript resulted in broadly distributed target gene silencing across the brain and spinal cord. Robust and durable silencing of β-catenin mRNA was observed after a single dose at day 31 post injection. Specifically, a single 72 mg dose (approximately 24 mg/kg) resulted in over 80 percent target silencing in the spinal cord and approximately 50 percent silencing across regions of the brain. Widespread distribution of the novel siRNA conjugate was observed across the CNS, including the frontal and temporal cortex, deep brain structures such as basal ganglia and dentate gyrus, cerebellum, brain stem and spinal cord, with evidence for cellular localization in neurons, astrocytes, and microglia. In additional rat studies, further optimization of novel conjugates was reported using siRNAs targeting superoxide dismutase 1 (SOD1), a genetically defined disease gene implicated in amyotrophic lateral sclerosis (ALS). Additional optimization of the conjugate design resulted in an over ten-fold improvement in potency, with a dose as low as 0.07 mg (approximately 0.25 mg/kg) resulting in approximately 50 percent SOD1 silencing across the CNS. In both rat and NHP studies, intrathecal administration of these novel siRNA conjugates was found to be generally well tolerated. Consistent with previous guidance, Alnylam expects to select its first CNS Development Candidate (DC) by the end of 2018 with an initial Investigational New Drug (IND) or equivalent application in late 2019 or early 2020.

Alnylam scientists also presented new preclinical results with novel siRNA conjugates targeting transthyretin (TTR), demonstrating delivery to ocular tissue in rats and NHPs. Efficient and durable silencing of ocular TTR mRNA in rat was achieved following a single intravitreal injection, with siRNAs localizing to the relevant cell types in the eye, retinal pigment epithelium (RPE) and ciliary epithelia (CE), where amyloid deposits can occur in approximately 10 percent of hereditary ATTR (hATTR) amyloidosis patients. The ocular target gene silencing effect was recapitulated in NHPs with approximately 98 percent silencing of TTR mRNA in RPE and near complete knockdown of TTR protein at day 31, as measured in immunohistochemical analyses. In NHP studies, there were no notable safety findings related to administration of ocular siRNA conjugates.

Additional OTS presentations by Alnylam scientists and collaborators included results on:

  • Further optimization of the Company’s enhanced stabilization chemistry plus (ESC+) conjugate platform
  • Safety evaluation of 2′-Fluoro-modified nucleotides embedded in GalNAc-conjugate siRNAs
  • Simultaneous silencing of two different gene transcripts with Bis-RNAi conjugates.

For the full breadth of results presented by the Company at OTS please visit the Capella section of the Alnylam website.

We are also pleased to share that Alnylam’s publication of results from the APOLLO Phase 3 pivotal trial of patisiran featured in the July 5, 2018 issue of The New England Journal of Medicine has been selected as the OTS “2018 Paper of the Year” – an award designed to honor the year’s most impactful paper in the field of oligonucleotide therapeutics.


Tagged with:

About author

Related Articles