Ionis in Novartis R&D tie-up, but comes as Biogen-partnered med cut

Novartis could pay out as much as $1 billion for the two CV meds should it hit all of its marks in testing and beyond.

Ionis has signed a $75 million upfront (with $1 billion in biobucks in the offering) with Novartis for two of the biotech’s heart drug candidates—a much-needed positive for Ionis, after it announced the pulling of another Big Pharma-partnered med just yesterday.

First up, to the Novartis deal, which sees $75 million upfront, a $100 million equity stake, and potentially around $1 billion in biobucks, should all go to plan, for Ionis and its subsidiary Akcea.

For this, the Swiss major gains an exclusive worldwide option and collab pact to work on and sell AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx, two drugs in the clinic for cardiovascular diseases.

Ionis and Akcea said in a statement that they plan to conduct a midstage dose-ranging test for each drug, in order to “choose the optimal dose and evaluate alternative dose schedules, such as monthly dosing, for the phase 3 study.” 

Should this pass muster, and before the start of the late-stage test, Novartis will under the deal be able to exercise its option to license and commercialize each drug.

In a recent phase 1/2 study in healthy volunteers with elevated lipoprotein(a), AKCEA-APO(a)-LRx produced “significant and sustained reductions in Lp(a) of up to 97% with mean reduction of 79% after only a single, small volume dose and with multiple doses, observed reductions of Lp(a) of up to 99% with a mean reduction of 92%,” according to Ionis.

AKCEA-APOCIII-LRx, meanwhile, is currently being tested in an early-stage human trial, again in healthy volunteers, specifically with elevated triglycerides.

This research deal will build on Novartis’ CV legacy that includes its once-major blockbuster Diovan (valsartan) and its more recent combo heart drug Entresto (sacubitril/valsartan).

“AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx are novel potential therapies to address the broad opportunities that still exist to treat cardiovascular disease, despite currently available therapies. We believe that Novartis is the ideal partner for developing both drugs to their fullest potential,” said Paula Soteropoulos, chief executive officer at Akcea Therapeutics, which has been running the development of these meds. 

“This strategic partnership allows us to move more rapidly to phase 3 cardiovascular outcomes studies with both therapies than our original development plan.”

Ionis has had something of a topsy-turvy start to the New Year: Over the Christmas break, it and Biogen gained FDA approval for the first-ever SMA drug Spinraza (nusinersen), but then the two quietly announced this week that one of its other collab drugs will be discontinued given its poor efficacy.

The med, IONIS-DMPK-2.5-R, has now been chopped due to inadequate potency in muscle in phase 1/2 in patients with myotonic dystrophy type 1.

The news was announced during an R&D update from Ionis this week, although at time of writing neither company had made this information available on their sites. The pair said they now plan to develop a muscle-targeting LICA alternative.

Analysts at Jefferies are less than impressed, however, with Ionis’ pipeline. In its pre-JPM release the firm said that its pipeline update this week “came short of drawing excitement beyond Spinraza.”

The firm added: “Beyond highly anticipated Spinraza launch (our 2021E sales of $1.6B vs. BIIB cons of $1.4B, implying royalties to IONS of ~$250M), we view current pipeline products unlikely to drive further meaningful appreciation in IONS shares from its already hefty valuation (EV of ~$5.5B).”

This includes its diabetes med IONIS-GCGR-Rx, which has seen Jefferies “question its therapeutics merits in a crowded marketplace,” and its other CV candidate volanesorsen, which Jefferies sees as having “limited market potential.” These comments were made before the Novartis deal was made public. 

After it was announced, analysts at Leerink were more upbeat, saying the deal "represents a clear positive surprise after a disappointing pipeline update call yesterday, where Ionis announced the discontinuation of DMPKr." It added: "More importantly, the deal is validating of Ionis' LICA platform, which seeks to enable lower volume and less frequent dosing."