Go or no go? Argenx's December showdown

The most valuable US approval decision left for 2021 concerns Argenx’s efgartigimod in myasthenia gravis. A green light is expected, but questions remain over how broad the label might be.

Calliditas could also gain its first US approval after a three-month delay with Nefecon. Meanwhile, Merck & Co’s Keytruda could bag its eighth FDA nod this year alone, this time in adjuvant melanoma. 

There is also a chance that Novartis gets closure next month for Leqvio, its cholesterol-lowering project which targets PCSK9 via RNA interference. The Pdufa date is January 1, nearly a year after the project received its knockback for manufacturing inspection-related issues. 

One step ahead 

Argenx’s efgartigimod, an anti-FcRn Ab fragment, impressed in its pivotal Adapt study in myasthenia gravis. Significantly more patients had improved symptoms than placebo, while safety looked hard to beat with similar rates of headache, stuffy nose and nausea in both arms. 

Myasthenia gravis (MG) is a neurological condition that causes certain muscles to weaken progressively. For around 85% of MG patients, autoantibodies against AChR drive the disease, and it was in these patients that Adapt's primary endpoint was measured. Therefore, a restriction to the AChR-positive population could be on the label. 

If given the greenlight, efgartigimod will be the first anti-FcRn agent on the market, but the space is fiercely competitive.  

UCB’s anti-FcRn antagonist rozanolixizumab has data in the first half of 2022, and as a subcutaneous injection it has a convenience advantage over efgartigimod’s IV infusion route. Argenx’s subcutaneous version is not far behind, however, and is being tested in a non-inferiority study called AdaptSC, which is due to report early next year.

Also J&J paid $6.5bn for Momenta last year, mainly for its anti-FcRn antagonist nipocalimab, although that project's phase 3 study in MG only started in July. Efgartigimod is one of the sector's most valuable unpartnered assets, according to Evaluate Pharma. 

The wait is over 

December will see a final decision on Calliditas’s Nefecon in IgA nephropathy after a three-month delay. The news of the extended timeline saw shares plummet 25% in September. 

Calliditas had to submit additional analysis on estimated glomerular filtration rate (eGFR). Nefecon was originally filed under the accelerated approval programme using proteinuria as a surrogate endpoint. 

Despite the delay Nefecon could still become the first approved therapy for IgA nephropathy, although Travere’s sparsentan is closing in. Travere plans to file for accelerated approval in the first quarter of next year based on interim data from the Protect study.  

Earlier therapy 

Keytruda could see its target adjuvant melanoma market doubled next month, with a decision due in stage IIB/IIC melanoma. Merck’s juggernaut already has an adjuvant label in stage III disease, a setting where the cancer has spread to the lymph nodes. For stage II the current practice after surgery is observation, but high-risk patients often experience disease recurrence.  

The Keynote-716 study, reported at Esmo, showed Keytruda cut the risk of disease relapse by 35% versus placebo (p=0.007). Safety will be a focus for the FDA as serious drug-related adverse events were seen in 16% of Keytruda versus 4% of placebo recipients, and the resulting discontinuation rates were 15% and 3% respectively.  

If approval is granted, this would be Keytruda’s fourth adjuvant setting in the US, following a green light in adjuvant renal cell cancer in mid November. 

Closure?

After shelling out $9.7bn on The Medicines Company in 2019 for Leqvio, Novartis and its investors will be keen to get the asset to the US market as soon as possible. The project achieved impressive LDL cholesterol-lowering in phase 3, and safety looked clean.

Initially, Leqvio was scuppered by an unresolved facility inspection at a contractor plant in Italy, so Novartis moved the manufacturing to the company’s own plant in Austria.  

Encouragingly, Leqvio was approved in Europe last December, but the rollout has been slow, with Novartis reporting sales of just $8m in the first nine months of the year. 

The tables below list first-time and supplementary US approvals, as well as advisory committee meetings due next month, with consensus forecasts from Evaluate Pharma.