Alnylam Announces New and Enhanced Framework for Value-Based Agreements to Accelerate Patient and Provider Access to GIVLAARI™ (givosiran)
− Framework Ties Payment for GIVLAARI to its Delivery of Patient Outcomes in the Real-World Setting -
− Includes New Approach Designed for Ultra-Rare Diseases that Gives Participating Payers Greater Financial Certainty if Disease Prevalence is Higher Than Anticipated –
- Discussions Underway with Leading Insurers and Agreement in Principle in Place with Harvard Pilgrim -
Alnylam is in active discussions with leading payers about VBAs for GIVLAARI and plans to incorporate this new ultra-rare disease framework into these discussions and negotiations. Alnylam has reached an agreement in principle with Harvard Pilgrim covering GIVLAARI.
Under this innovative framework for VBAs, participating government and commercial payers will pay the full value for GIVLAARI only when it delivers patient outcomes in the real-world setting similar to results demonstrated in clinical trials. An additional and newly designed Prevalence-Based Adjustment (PBA) feature will trigger rebates to participating payers if the number of diagnosed patients they cover exceeds current epidemiologic estimates for AHP. There are often uncertainties in diagnosis rates and disease prevalence estimates in ultra-rare diseases, making it challenging for payers to predict the number of patients who will be covered within their plans. This innovative approach offers greater certainty to payers that their overall financial risk will be adjusted if a substantially larger number of patients than currently estimated are identified, diagnosed, and treated with GIVLAARI.
“Patients can sometimes experience lengthy delays waiting for access when a new medicine becomes available, as payers can be challenged to determine both which patients may best respond and the number of potentially undiagnosed patients in their plans,” said
Currently, the population of AHP patients with diagnosed, active disease in the U.S. and
"Harvard Pilgrim applauds Alnylam’s efforts to help us manage plan members’ costs if the number of patients treated exceeds initial forecasts based upon existing prevalence models,” said
“Express Scripts, Accredo, and
In the absence of GIVLAARI, an AHP patient can cost
Alnylam’s Patient Access Philosophy
The new VBA framework announced today for ultra-rare diseases such as AHP builds upon Alnylam’s Patient Access Philosophy, first released nearly a year ahead of the approval of its first RNAi therapeutic. As part of Alnylam’s Access Philosophy, the Company commits to not increase the price of GIVLAARI by more than the consumer price index for urban consumers (CPI-U), a measure of inflation, in the absence of significant investment associated with a meaningful label expansion. Commercially insured patients are expected to have little-to-no out-of-pocket costs for GIVLAARI. To see Alnylam’s progress as of
Alnylam is deeply committed to helping patients with AHP get access to GIVLAARI. A comprehensive patient support services program, Alnylam Assist®, will offer an in-house team of Case Managers to assist patients with verification of insurance benefits and financial assistance for those who qualify. Patients will also be eligible to receive support from Patient Education Liaisons, who can answer questions about disease and treatment. Physicians and patients can learn more about Alnylam’s comprehensive patient services by visiting AlnylamAssist.com or call 1-833-256-2478.
GIVLAARI Important Safety Information
GIVLAARI is contraindicated in patients with known severe hypersensitivity to givosiran. Reactions have included anaphylaxis.
Anaphylaxis has occurred with GIVLAARI treatment (<1% of patients in clinical trials). Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVLAARI and institute appropriate medical treatment.
Transaminase elevations (ALT) of at least 3 times the upper limit of normal (ULN) were observed in 15% of patients receiving GIVLAARI in the placebo-controlled trial. Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment.
Measure liver function tests prior to initiating treatment with GIVLAARI, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter. Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations. In patients who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly. The dose may be increased to the recommended dose of 2.5 mg/kg once monthly if there is no recurrence of severe or clinically significant transaminase elevations at the 1.25 mg/kg dose.
Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with GIVLAARI. In the placebo-controlled study, 15% of patients receiving GIVLAARI experienced a renally-related adverse reaction. The median increase in creatinine at Month 3 was 0.07 mg/dL. Monitor renal function during treatment with GIVLAARI as clinically indicated.
Injection Site Reactions
Injection site reactions were reported in 25% of patients receiving GIVLAARI in the placebo-controlled trial. Symptoms included erythema, pain, pruritus, rash, discoloration, or swelling around the injection site. One (2%) patient experienced a single, transient, recall reaction of erythema at a prior injection site with a subsequent dose administration.
Concomitant use of GIVLAARI increases the concentration of CYP1A2 or CYP2D6 substrates, which may increase adverse reactions of these substrates. Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates for which minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.
The most common adverse reactions that occurred in patients receiving GIVLAARI were nausea (27%) and injection site reactions (25%).
For additional information about GIVLAARI, please see full Prescribing Information.
About GIVLAARI™ (givosiran)
GIVLAARI is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of adults with acute hepatic porphyria (AHP). In the pivotal study, GIVLAARI was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or IV hemin administration at home compared to placebo. GIVLAARI is Alnylam’s first commercially-available therapeutic based on its Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of aminolevulinic acid synthase 1 (ALAS1) messenger RNA (mRNA), leading to reduction of toxins associated with attacks and other disease manifestations of AHP. For more information about GIVLAARI, visit GIVLAARI.com.
Acute hepatic porphyria (AHP) refers to a family of ultra-rare, genetic diseases characterized by potentially life-threatening attacks and, for some patients, chronic manifestations that negatively impact daily functioning and quality of life. AHP is comprised of four types: acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), variegate porphyria (VP), and ALA dehydratase-deficiency porphyria (ADP). Each type of AHP results from a genetic defect leading to deficiency in one of the enzymes of the heme biosynthesis pathway in the liver. AHP disproportionately impacts women of working and childbearing age, and symptoms of the disease vary widely. Severe, unexplained abdominal pain is the most common symptom, which can be accompanied by limb, back, or chest pain, nausea, vomiting, confusion, anxiety, seizures, weak limbs, constipation, diarrhea, or dark or reddish urine. The nonspecific nature of AHP signs and symptoms can often lead to misdiagnoses of other more common conditions such as viral gastroenteritis, irritable bowel syndrome (IBS), addiction withdrawal and appendicitis. Consequently, patients with AHP can wait up to 15 years for a confirmed diagnosis. In addition, long-term complications and comorbidities of AHP can include hypertension, chronic kidney disease or liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma.
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.
Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views with respect to the approval of GIVLAARI™ (givosiran) injection for subcutaneous use, and the implications of such approval for patients and their caregivers, its plans to offer a new and enhanced framework for VBAs designed to help patients with AHP gain access to GIVLAARI and , the status of discussions with leading payers about VBAs for GIVLAARI that would incorporate this framework, expectations regarding the estimated population of AHP patients with diagnosed, active disease in the U.S. and
Alnylam Pharmaceuticals, Inc.
Christine Regan Lindenboom
(Investors and Media)