Biotechnology Events


Alnylam Pharmaceuticals Inc.


Akshay Vaishnaw, M.D., Ph.D., SVP, Clinical Research, gave guidance for the start of the phase-III program for Givosiran. He stated, "We've now been engaged with both FDA and EMA in discussions on our phase-III study design and our overall efforts to bring Givosiran to patients as rapidly as possible. As a next step, we look forward to the start of our phase-III program expected in late 2017."
Source: Q2 2017 earnings conference call, 8/09/17


Alnylam Reports New Positive Clinical Results for Givosiran (ALN-AS1), an Investigational RNAi Therapeutic for the Treatment of Acute Hepatic Porphyrias

- In Randomized, Double-Blind, Placebo-Controlled Study, Givosiran Demonstrates Decreased Annualized Attack Rate and Hemin Usage -

- Initial Results from Ongoing Open Label Extension (OLE) Study Show Consistent Reductions in Porphyria Attacks with Continued Givosiran Treatment -

- Givosiran Administration Generally Well Tolerated with Treatment up to 12 Months -

- Company Plans to Initiate Phase 3 Clinical Program in Late 2017 -

- Management to Discuss New Clinical Data in Webcast Conference Call Today, Monday, June 26th at 8:00 a.m. ET -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), the leading RNAi therapeutics company, announced today new positive interim results from Part C, cohorts 1-3, of its ongoing double-blind, randomized, placebo-controlled Phase 1 study, in addition to initial results from an open-label extension (OLE) study with givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias. These results were presented today in an oral presentation at the 2017 International Congress on Porphyrins and Porphyrias (ICPP), being held from June 25 - 28, 2017 in Bordeaux, France. Results provide evidence that givosiran has the potential to prevent porphyria attacks in patients with acute intermittent porphyria (AIP) suffering with recurrent attacks. Based on initial results from the OLE study, prolonged administration of givosiran appears to be associated with consistent reductions in the incidence of porphyria attacks. Givosiran administration was generally well tolerated with up to 12 months of treatment. In addition, the Company plans to present updated results from the EXPLORE natural history study of patients with acute hepatic porphyria who experience recurrent attacks.

"The acute hepatic porphyrias are a family of ultra-rare, under-diagnosed diseases caused by mutations in the heme synthesis pathway resulting in debilitating acute attacks and chronic manifestations including severe pain, and changes in mental status and weakness. There is significant unmet medical need for novel therapies that could prevent acute attacks and improve chronic disease manifestations," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D at Alnylam. "We believe these new interim results continue to demonstrate the potential for givosiran to achieve meaningful reductions in the frequency of porphyria attacks, as well as demonstrate tolerability with extended dosing. We look forward to further exploring givosiran's clinical activity and safety profile as we complete Part C of the Phase 1 study, which is now fully enrolled, and continue dosing in the OLE study."

"We believe that a long acting therapeutic agent that has the potential to prevent porphyria attacks and that can be administered via a once monthly, low volume, subcutaneous injection could be a potentially transformative treatment option for patients suffering with this debilitating and potentially life-threatening disease," said Jeff Miller, General Manager of the givosiran program. "Based on these encouraging interim results and with both Breakthrough Therapy and PRIME designations granted, we will continue to work with global regulatory authorities to rapidly advance givosiran toward regulatory filings and, if approved, to patients. To that end, we remain on track to initiate the givosiran Phase 3 program in late 2017."

New results presented at ICPP include all available data from cohorts 1-3 in Part C of the Phase 1 trial (N=12) and cohorts 1 and 2 (N=8) of the OLE study as of the data cutoff date of April 21, 2017. Givosiran achieved potent silencing of the ALAS1 mRNA, which resulted in robust and durable lowering of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic heme intermediates that mediate acute attacks and chronic porphyria symptoms. In the first three unblinded treatment cohorts from Part C, givosiran-treated patients (N=9) experienced a mean 63 percent reduction in the annualized number of all porphyria attacks relative to the run-in period attack rate, with consistent effects observed across a wide range of baseline attack rates. Evaluating only attacks that were treated at a healthcare facility or with hemin, givosiran administration was associated with a mean 73 percent reduction in annualized attack rate relative to placebo during the treatment period. In addition, a 73 percent mean decrease in annualized hemin doses relative to the run-in period was reported. Finally, in a new analysis, the observed reduction in annualized attack rate was found to be associated with the degree of ALA and PBG lowering.

Initial results from cohorts 1 and 2 (N=8) of the givosiran OLE study were also presented; to date, all eligible patients have rolled over from the Phase 1 study to the OLE study. Longer-term treatment with givosiran was associated with consistent reductions in the annualized porphyria attack rate. In addition, preliminary evidence was obtained suggesting the potential for further reductions in the attack rate with extended dosing. Specifically, for the six OLE patients randomized to receive givosiran in Phase 1, the mean annualized attack rate during the Phase 1 treatment period was nine and this was reduced further to five in the OLE study with a mean follow up of 111 days. Further, in the two OLE patients randomized to receive placebo in Phase 1, no attacks have occurred as of the data cut-off date following givosiran administration in the OLE study, with a mean follow up of 31 days. The Company expects to continue enrollment and dosing of patients in the OLE study, and plans on reporting results at least once annually.

As of the data cutoff date, givosiran administration was generally well tolerated in recurrent attack AIP patients in cohorts 1-3 in Part C of the Phase 1 study and in cohorts 1 and 2 of the ongoing OLE study, with a mean of 169 and 111 days on study, respectively, and up to 12 months on givosiran. In Part C there were no drug-related serious adverse events (SAEs) or discontinuations due to adverse events (AEs). Excluding porphyria attacks, three patients had four SAEs; none were assessed as related to study drug. As previously reported, one death occurred in a patient in cohort 3 in the givosiran arm due to hemorrhagic pancreatitis complicated by a pulmonary embolism and following a recent hospitalization for bacteremia; the death was considered to be unlikely related to study drug by the investigator and the study's Safety Review Committee. During the Phase 1 treatment period, all randomized patients reported at least one AE. The majority of AEs were assessed as mild or moderate in severity. Twenty-five percent of patients had severe AEs, assessed as unrelated to study drug. AEs in three or more patients included: abdominal pain, headache, nasopharyngitis, nausea and vomiting. Four patients were assessed as having AEs possibly related to study drug, including injection site reaction (mild and self-limiting), hypersensitivity, myalgia, headache, moderate renal impairment (in a patient with a history of moderate renal impairment) and erythema. There were no other clinically significant changes in vital signs, electrocardiograms, clinical laboratory parameters (including liver function tests and lipase tests), or physical examination. The overall safety experience in the ongoing OLE study was consistent with results from the Phase 1 study. No SAEs (excluding porphyria attacks) or discontinuations due to AEs have been reported in the OLE study.

Data from the EXPLORE natural history study will also be presented at the conference. EXPLORE is a prospective, multinational, observational study characterizing the natural history and clinical management of AHP patients with recurrent attacks (3 or more attacks/year) or who receive hemin or gonadotropin-releasing hormone analogue prophylaxis to prevent attacks. A total of 112 patients with acute hepatic porphyria (AHP), of which 104 have AIP, were enrolled from 13 countries. Updated 12-month data from EXPLORE demonstrate that patients suffer from both acute attacks and chronic symptoms (64 percent of patients) in between attacks, that together result in a diminished quality of life. The annualized attack rate on study was approximately five attacks/person with a mean attack duration of seven days. The majority of attacks (77 percent) required treatment in the hospital, urgent healthcare facility or with hemin. An analysis of costs associated with AHP and recurrent attacks - the first analysis of its kind in AHP in the U.S. - revealed the average estimated annual expenditure per patient ranges from approximately $400,000 to $650,000. These analyses only incorporate direct costs, and do not reflect indirect costs, such as the cost associated with lost productivity for both patients and caregivers. Updated EXPLORE data will be presented on Wednesday, June 28th and the presentations will be posted to the Alnylam website in the Capella section.
Source: press release, 6/26/17.


FDA Grants Breakthrough Therapy Designation for Alnylam's Givosiran for the Prophylaxis of Attacks in Patients with Acute Hepatic Porphyria

- Additional Phase 1 Results to be Presented at the International Congress on Porphyrins and Porphyrias (ICPP), June 25 - 28, 2017 -

- Company Plans to Initiate Phase 3 Clinical Program in Late 2017 -

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that it has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for givosiran (ALN-AS1), an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the prophylaxis of attacks in patients with acute hepatic porphyria (AHP). Breakthrough Therapy designation is granted to expedite the development and review of new drugs that treat serious or life-threatening diseases where preliminary clinical evidence exists in support of substantial benefit over available therapies. The designation is aimed to help ensure that patients with unmet medical needs receive access to new therapies through FDA approval as soon as possible.

"Patients with acute hepatic porphyrias, a family of ultra-rare diseases, suffer from severe neurovisceral attacks often resulting in hospitalization, and chronic, debilitating symptoms that impair daily function. This FDA decision is recognition of both the need for novel therapeutic options and the promising initial results with givosiran," said Jeff Miller, Vice President, General Manager, Givosiran Program at Alnylam. "We believe givosiran could become a transformative treatment for patients with this devastating and potentially life-threatening disease. Accordingly, we look forward to rapidly advancing this program in collaboration with global regulatory authorities, having also received PRIME designation from the European Medicines Agency earlier this year. We plan to initiate the Phase 3 clinical program with givosiran in late 2017."

Promising results from the ongoing Phase 1 study of givosiran demonstrating meaningful reductions in the occurrence of porphyria attacks formed the basis of the Breakthrough application. Updated results from this trial will be provided in an oral presentation on June 26, 2017 at the International Congress on Porphyrins and Porphyrias (ICPP) being held in Bordeaux, France.
Source: press release, 5/31/17.


Compound/DeviceSpecialtyIndicationCompound ClassTarget
Givosiran (ALN-AS1)Medical GeneticsAcute hepatic porphyrias (AHP)RNAi therapeuticAminolevulinic acid synthase 1 (ALAS1)a

Mechanism of action: Givosiran (ALN-AS1), a subcutaneously administered, investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias, including acute intermittent porphyria (AIP). AIP is the most common of the porphyrias, an ultra-rare autosomal dominant disease caused by loss of function mutations in porphobilinogen deaminase (PBGD), an enzyme in the heme biosynthesis pathway that can result in accumulation of toxic heme intermediates, including aminolevulinic acid (ALA) and porphobilinogen (PBG). Givosiran is an ESC-GalNAc-siRNA conjugate targeting ALAS1, a liver-expressed, rate-limiting enzyme upstream of PBGD in the heme biosynthesis pathway. Inhibition of ALAS1 is known to reduce the accumulation of heme intermediates that cause the clinical manifestations of AIP.

Phase of Development: I

Event Type: Program status: Initiation of phase III trial

Dates: 2017-12-01 - 2017-12-31

Results: Pending