January 6, 2016: Ionis Pharmaceuticals and Akcea Therapeutics, a wholly-owned subsidiary of Ionis Pharmaceuticals, Inc., announced an exclusive, worldwide option and collaboration agreement with Novartis to develop and commercialize AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx. Ionis and Akcea are eligible to receive $225 million in near-term payments, including an immediate $75 million upfront option payment and a $100 million equity investment in Ionis, which equates to 1,631,435 shares at $61.30 per share. Ionis and Akcea are also eligible to receive a license fee as well as development, regulatory and commercial milestone payments as each drug advances. Also, Ionis and Akcea are eligible to receive tiered royalties in the mid-teens to low twenty percent range on net sales of each drug.
Ionis and Akcea plan to conduct a Phase 2 dose-ranging study for each drug, to choose the optimal dose and evaluate alternative dose schedules, such as monthly dosing, for the Phase 3 study. Following the successful completion of each Phase 2 dose-ranging study, and before initiation of the Phase 3 study, Novartis will be able to exercise its option to license and commercialize each drug.
For each drug, upon option exercise, Novartis will pay Ionis and Akcea a $150 million license fee, will initiate a global Phase 3 cardiovascular outcome study in a high-risk population and will be responsible for worldwide development and commercialization activities. Akcea retains the right to co-commercialize any successful drug through its specialty sales force focused on lipid specialists on terms and conditions to be agreed with Novartis. Ionis and Akcea are also eligible to receive up to $315 million and $265 million in development and regulatory milestone payments for AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx, respectively, as well as up to $285 million and $265 million in commercialization milestone payments, for each drug, respectively. Novartis has an obligation to make a further equity investment of $50 million in the next 18 months in either Ionis at the same premium as the initial investment or in Akcea.
January 04, 2017: Ionis Pharmaceuticals announced positive data from a Phase 2 study of IONIS-GCGRRx in 79 patients with type 2 diabetes. In this study, patients with type 2 diabetes uncontrolled on stable, maximal metformin therapy treated with IONIS-GCGRRx achieved robust and sustained, statistically significant improvements in hemoglobin A1c (HbA1c) and other measures of glucose control after 26 weeks of treatment.
– Patients treated with 50 mg and 75 mg weekly doses achieved mean reductions in HbA1c of 0.7 percentage points (p 3x upper limit of normal [ULN]) increases in liver enzymes observed. In the 75 mg cohort, three patients experienced alanine aminotransferase (ALT) elevations >3x ULN that resolved with dose reduction. In the study, IONIS-GCGRRx was safe and well tolerated. In both cohorts, there were no clinically meaningful changes in lipids, blood pressure, body weight, gastrointestinal symptoms or cases of hypoglycemia. There were no flu-like symptoms, abnormalities in renal function, or clinically meaningful platelet events observed. The majority of adverse reactions reported were mild. The most common reported was a low incidence of injection site reactions (4.4% of injections).
Volanesorsen is an antisense drug in development for two rare metabolic disorders: FCS and FPL. Volanesorsen is designed to reduce the production of ApoC-III, a protein produced in the liver that plays a central role in the regulation of plasma triglycerides and may also affect other metabolic parameters.
An incredible 82% of patients treated with Volanesorsen, including three of the FCS patients, achieved triglyceride levels less than 500 mg/dl after 13 weeks of treatment, compared to 14% of placebo-treated patients.
December 28, 2016: BMO Capital raises price target on Ionis Pharmaceuticals to $68 from $61.
December 23, 2016: The FDA approves first drug for spinal muscular atrophy. The Food and Drug Administration today approved Spinraza (nusinersen), the first drug approved to treat children and adults with spinal muscular atrophy (SMA), a rare and often fatal genetic disease affecting muscle strength and movement. Spinraza is an injection administered into the fluid surrounding the spinal cord.
Spinraza is marketed by Biogen of Cambridge, Massachusetts and was developed by Ionis Pharmaceuticals of Carlsbad, California.
The FDA worked closely with the sponsor during development to help design and implement the analysis upon which this approval was based. The efficacy of Spinraza was demonstrated in a clinical trial in 121 patients with infantile-onset SMA who were diagnosed before six months of age and who were less than seven months old at the time of their first dose. Patients were randomized to receive an injection of Spinraza, into the fluid surrounding the spinal cord, or undergo a mock procedure without drug injection (a skin prick). Twice the number of patients received Spinraza compared to those who underwent the mock procedure. The trial assessed the percentage of patients with improvement in motor milestones, such as head control, sitting, ability to kick in supine position, rolling, crawling, standing and walking.
The FDA asked the sponsor to conduct an interim analysis as a way to evaluate the study results as early as possible; 82 of 121 patients were eligible for this analysis. Forty percent of patients treated with Spinraza achieved improvement in motor milestones as defined in the study, whereas none of the control patients did.
Additional open-label uncontrolled clinical studies were conducted in symptomatic patients who ranged in age from 30 days to 15 years at the time of the first dose, and in presymptomatic patients who ranged in age from 8 days to 42 days at the time of the first dose. These studies lacked control groups and therefore were more difficult to interpret than the controlled study, but the findings appeared supportive of the clinical efficacy demonstrated in the controlled clinical trial in infantile-onset patients.
The most common side effects found in participants in the clinical trials on Spinraza were upper respiratory infection, lower respiratory infection and constipation. Warnings and precautions include low blood platelet count and toxicity to the kidneys (renal toxicity). Toxicity in the nervous system (neurotoxicity) was observed in animal studies.
The sponsor is receiving a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive priority review of a subsequent marketing application for a different product. This is the eighth rare pediatric disease priority review voucher issued by the FDA since the program began.
December 22, 2016: Ionis Pharmaceuticals announced today that it has earned a $5 million milestone payment from Janssen Biotech, Inc. associated with the validation of an undisclosed target to treat patients with a gastrointestinal (GI) autoimmune disease. Under the collaboration, Ionis and Janssen will continue to evaluate the target with the goal of advancing an antisense drug into development.Under the terms of the agreement, which covers three programs, Ionis is eligible to receive nearly $800 million in development, regulatory and sales milestone payments and license fees. In addition, Ionis will receive tiered royalties that on average are double-digits on sales from any product that is successfully commercialized.
December 19, 2016: Ionis Pharmaceuticals announced today that it has advanced its lead drug candidate IONIS-AZ4-2.5-LRx, which has now been renamed AZD8233, into preclinical development. AZD8233 is designed to inhibit an undisclosed target to treat cardiovascular disease and is also the first of a new class of antisense drugs that uses both Ionis’ proprietary Generation 2.5 chemistry and its LIgand Conjugated Antisense or LICA technology. In conjunction with this milestone, Ionis earned a $25 million milestone payment from AstraZeneca.
As AZD8233 advances in development, Ionis will be eligible to receive up to $300 million in additional development and regulatory milestone payments as well as tiered, low double-digit royalties from sales of the drug. AstraZeneca will be responsible for further developing and commercializing AZD8233.
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Ionis is the leading company in RNA-targeted drug discovery and development focused on developing drugs for patients who have the highest unmet medical needs, such as those patients with severe and rare diseases. Using its proprietary antisense technology, Ionis has created a large pipeline of first-in-class or best-in-class drugs, with over a dozen drugs in mid- to late-stage development.
Ionis Pharmaceuticals CEO was on Mad Money on December 20, 2016: