Watch out, Pfizer and Alnylam. AstraZeneca wades deeper into rare diseases with Ionis tie-up

Just months after wrapping up the Alexion acquisition, AstraZeneca is beefing up its newly established rare disease portfolio with a collaboration with Ionis Pharmaceuticals, targeting a condition where Pfizer and Alnylam are also competing.

For $200 million upfront, AstraZeneca is licensing Ionis’ eplontersen, the California biotech’s second shot at the rare disease transthyretin amyloidosis (ATTR) after a rather lackluster performance by its predecessor Tegsedi. Up to $485 million in development and approval milestones, plus another $2.9 billion payment tied to sales, are up for grabs.

Eplontersen is currently in phase 3 testing. If eventually approved, the antisense drug could compete with Alnylam’s RNA interference therapy Onpattro and Pfizer’s fast-growing Vyndamax. Wall Street thinks eplontersen can generate $1.3 billion in 2030 sales, SVB Leerink analyst Mani Foroohar said in an October note to clients.

An estimated 300,000 to 500,000 patients have ATTR around the globe, according to Ionis. Although characterized as a rare disease, ATTR might not be as rare as people might think. Pfizer, for one, has suggested ATTR might be a more prevalent disease that’s being under-diagnosed. Thus, driving disease awareness and diagnosis has been a key strategy for Pfizer’s launch of Vyndamax.

That approach is paying off. In the first nine months of 2021, Vyndamax and sister med Vyndaqel brought in global sales of $1.45 billion, up 66% year over year.

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With the Ionis deal, AZ is basically offering its commercial clout. Ionis will continue to lead the two phase 3 trials in ATTR polyneuropathy and cardiomyopathy, which affect the nervous system and the heart, respectively. ATTR-PN is expected to be the first indication, with an FDA filing expected in 2022. AZ will also be responsible for a potential ATTR-CM filing. In heart disease, AZ currently sells blockbuster SGLT-2 inhibitor Farxiga, blood thinner Brilinta and aging cholesterol med Crestor.

AZ will also take over manufacturing for commercial supply. The two will collaborate on sales and marketing activities in the U.S., while AZ has exclusive rights ex-U.S. except certain Latin American countries.

Combining Ionis’ technology with “AstraZeneca's global scale and leadership in cardiovascular drug development and commercialization will enable faster and deeper market penetration for the benefit of patients,” Ionis CEO Brett Monia, Ph.D., said in a statement Tuesday.

The relationship between the two companies predates the eplontersen deal. The two started with a cancer-focused pact signed in 2012. Then in 2015, AZ and Ionis formed a strategic collaboration to work on antisense therapies for cardiovascular, metabolic and kidney diseases. AZ has previously licensed earlier-stage pipeline candidates from Ionis, including one for NASH and one for a genetically associated form of kidney disease.

For Ionis, the deal is a needed injection of confidence in its antisense platform. The company just suffered a blow in October when tofersen, an antisense candidate licensed to Biogen, failed a pivotal study for SOD1 amyotrophic lateral sclerosis.

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Ionis’ earlier-generation Tegsedi is only approved in hereditary ATTR-PN. Thanks to its limited label and some safety concerns, the drug’s market performance has been disappointing. Ionis recently shed Tegsedi’s North American marketing to Sobi.

Interestingly, AstraZeneca just reportedly blocked an investor group's $8 billion take-private deal for Sobi because of competition concerns and because the British pharma considered buying certain Sobi assets, Bloomberg reported. The Swedish rare disease player also holds U.S. rights to AZ’s respiratory syncytial virus drug Synagis.

AZ has only recently developed an interest in rare diseases with its purchase of Alexion. In ATTR, AZ is getting into a more crowded space. Besides Vyndamax and Onpattro, Alnylam is also working on a second-generation RNAi therapy called vutrisiran, which the Street estimates can generate $3.6 billion by 2030, according to Foroohar. BridgeBio has acoramidis, which is also in phase 3 testing.