Ionis/Akcea's Pfizer-partnered antisense drug shows promise in study, with implications for Arrowhead RNAi asset — analysts
Pfizer forked over $250 million upfront to license an antisense asset from Akcea and its sister company Ionis last year. On Wednesday, the large US drugmaker got a taste of what it has invested in.
The two developers said the drug — AKCEA-ANGPTL3-LRx — met the main goal of significantly lowering triglyceride levels in patients with hypertriglyceridemia, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).
Antisense drugs are engineered to interrupt the production of disease-causing proteins by targeting the specific corresponding messenger RNA (mRNA) that encodes that protein, thereby manipulating protein production. AKCEA-ANGPTL3-LRx is designed to reduce the production of angiopoietin-like 3 protein (ANGPTL3) in the liver, a key regulator of triglycerides, cholesterol, glucose and energy metabolism.
The 105-patient, placebo-controlled mid-stage study also showed the therapy induced dose-dependent reductions in ANGPTL3, apoC-III (a protein made by the liver that plays a key role in the regulation of serum triglycerides), very low-density lipoprotein, bad cholesterol and total cholesterol.
“Finally, and perhaps equally impactful regarding the future direction of the program, no reductions in liver fat or decreases in A1C were observed, rendering it less likely that the medicine is positioned for NAFLD or type 2 diabetes (each were initially laid out as possibilities when the PFE deal was struck),” Stifel’s Paul Matteis wrote in a note.
“We believe full data will be enlightening regarding how this drug stacks up against others in the Ionis/Akcea pipeline and more broadly in the CV space; management views the drug as differentiated from APOCIIILRx, which may become clear when we see more details regarding specific lipid changes.”
Only days ago, Akcea and Ionis unveiled Phase II data on AKCEA-APOCIII-LRx, another experimental antisense drug, which Novartis had an option on. The high dose of the therapy surpassed the placebo’s impact in significantly reducing triglycerides; in addition, it also slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting good cholesterol levels.
In December, Novartis decided to walk away from AKCEA-APOCIII-LRx — about a month after the Swiss drugmaker struck a $9.7 billion deal to swallow The Medicines Company. The New Jersey-based company’s PCSK9 drug inclisiran is powered by Alnylam’s RNAi technology that allows for high efficacy in lowering LDL with infrequent doses — and is being positioned as a formidable rival to the existing PCSK9 therapies from Amgen and Regeneron/Sanofi.
But early in 2019, Novartis did elect to take over the late-stage development of Akcea/Ionis’ asset — AKCEA-APO(a)-L — months after they revealed the therapy could slash lipoprotein (a) levels significantly in at-risk cardio patients in a Phase II study.
Pfizer tied up with Akcea/Ionis in October in a deal that made the two drugmakers eligible to receive up to $1.3 billion in milestone payments, in addition to double-digit royalties.
Detailed data on the AKCEA-ANGPTL3-LRx program will be unveiled by Pfizer sometime later in 2020, Akcea said on Wednesday.
Since the preliminary Akcea/Ionis data makes it unlikely AKCEA-ANGPTL3-LRx will work for type 2 diabetes and NAFLD, the data could have an impact on competitor Arrowhead Pharmaceuticals RNAi drug, ARO-ANG3, analysts said.
“For competitor ARWR – still in early-stage studies – this evidence of limited applicability of ANGPTL3 narrows the opportunity for ARO-ANG3 to dyslipidemia – an overlapping target population with its other early-stage assets – in the face of large pharma competitors with a multi-year head start,” SVB Leerink’s Mani Foroohar said.
But Baird’s Madhu Kumar was more optimistic, suggesting ARO-ANG3 will likely prove superior to the Akcea/Ionis antisense drug.