Sanofi’s Admelog (biosimilar insulin lispro) receives tentative FDA approval, pending resolution of patent issues – September 5, 2017

Sanofi announced Friday that the FDA has granted tentative approval to the company’s biosimilar insulin lispro (Lilly’s rapid-acting Humalog) under brand name Admelog. To our knowledge, the company has largely kept this US submission under wraps – even as the product received a positive CHMP opinion and was then EMA-approved (EU brand name: Insulin lispro Sanofi), Sanofi management shared no details on timing for an FDA submission. Perhaps the silence could be explained in part by patent issues still unresolved with Lilly. According to Sanofi’s announcement, Admelog has met all regulatory requirements for commercial approval (including positive phase 3 data in type 1 and type 2 diabetes), but will not hit pharmacy shelves until all patent infringement disputes are settled. It’s unclear at this point how long patent discussions may continue, and how long patients/providers will have to wait for this biosimilar mealtime insulin to be available, but we note that Merck management was similarly quiet about tentative FDA approval of Lusduna Nexvue (biosimilar basal insulin glargine, Sanofi’s Lantus) on the company’s 2Q17 earnings call, perhaps because the product won’t impact revenue in the near-term future. Lusduna Nexvue’s full approval is contingent on (i) Merck/Sanofi reaching an agreement, (ii) a court deciding in favor of Merck, or (iii) 30 months elapsing since filing of the lawsuit, and we imagine that Sanofi’s Admelog faces a similar situation and timeline for full US approval, though minimal details have been disclosed.

If/when fully approved, Sanofi’s biosimilar insulin lispro could make a big splash on the market, and in diabetes care. Insulin lispro Sanofi was the first-to-market biosimilar mealtime insulin, and Admelog could very well become the first biosimilar mealtime insulin in the US. As far as we are aware, the only other candidates are Biocon/Mylan’s preclinical biosimilar insulin lispro and biosimilar insulin aspart (Novo Nordisk’s NovoRapid).  ADA’s Chief Scientific, Medical, and Mission Officer Dr. William Cefalu emphasized at Keystone 2017 that biosimilars can offer similar benefits at a substantially reduced cost – and, he underscored, cost considerations cannot be ignored in modern diabetes care. It is certainly true that we want patients to be able to access all optimal drugs and technology, not just insulin. While some point out that the cost-saving of biosimilar insulins approved to-date, namely Lilly/BI’s Basaglar (biosimilar insulin glargine), hasn’t been as dramatic as we might’ve hoped, others advise patience, since past experience suggests that at least two generics are necessary on the market before any appreciable dip in prices (we personally doubt that such a formulaic approach is correct, particularly given the little history in this area). We certainly hope that Merck’s Lusduna Nexvue and Sanofi’s Admelog can help improve access to insulin in the US. HCPs have shown some reluctance to prescribe insulin biosimilars to date, which is understandable, since there is little safety or comparative effectiveness data available on biosimilar insulin to date. That said, we were pleased to see strong phase 3 results on biosimilar insulin lispro at ADA 2017, and we anticipate that Sanofi’s long history and expertise in insulin manufacturing will also support patient, provider, and payer confidence in Admelog.

• Two posters at ADA 2017 displayed (i) one-year results from SORELLA 1 (n=507 patients with type 1 diabetes) and (ii) 26-week data from SORELLA 2 (n=505 patients with type 2 diabetes). Both studies showed comparable safety/efficacy of Sanofi’s biosimilar insulin lispro vs. Lilly’s Humalog, with a primary endpoint of A1c reduction and secondary endpoints such as postprandial glucose, hypoglycemia, and adverse events. Together, the findings from >1,000 people with diabetes made a compelling case for the agent’s non-inferiority to Humalog, as well as its safety/tolerability, leading to the FDA’s tentative approval.
• On the payer side, we wonder if PBMs will take to biosimilar mealtime insulin as they did to biosimilar basal insulin (though this is all speculation for now, while we await Admelog’s full approval for the commercial market). CVS Health and UnitedHealthcare (two major PBMs in the US) have excluded Sanofi’s Lantus on their 2017 and 2018 formularies in favor of Lilly/BI’s biosimilar Basaglar, while the third major PBM Express Scripts places Lantus and Basaglar on equal footing. A similar trajectory for Admelog could bring substantial tailwinds for Sanofi’s insulin business, headwinds for Lilly’s.
• Admelog could serve to at least partly re-vitalize Sanofi’s diabetes business, which has posted sluggish sales in recent quarters: Portfolio revenue fell 11% YOY to $1.8 billion in 2Q17, after falling 4% YOY in 1Q17 and falling 3% YOY for the full-year 2016 (to $9.7 billion). Importantly, declining Lantus revenue has been the leading driver for this downward trend, so another insulin product could be meaningful in helping the company sustain or grow share in the diabetes market although from our view, the near-term market for MDI is not growing – indeed, GLP-1 and SGLT-2 inhibitors have taken the place of mealtime insulin for many people although we do believe they are also resulting in a longer lifecycle for diabetes medications overall. To be sure, Sanofi still boats a massive diabetes business, and we’d love to see Admelog ultimately help return the portfolio to growth, though we expect this biosimilar won’t affect reported revenue much less profitability for quite some time. First, it has to receive full approval with all patent issues from Lilly settled. Even then, as we’ve learned from the Basaglar rollout, it will take some time to educate HCPs on the safety and comparable efficacy of this new biosimilar vs. Humalog and Novolog, insulins that are familiar to many, from other reliable, experienced insulin manufacturers. On the other hand, we hope that by the time Admelog does become available in US pharmacies, real-world patients/providers are better-acquainted with the concept of biosimilar insulin, in general, and with the safety data on Sanofi’s biosimilar insulin lispro, specifically. Going head to head against Lilly and Novo Nordisk on a product that is in decline in some segments will be challenging and unlike basal insulin, mealtime insulin doesn’t have as much a growth trajectory at present though we do believe the category will expand overall over time.

Close Concerns Questions

Q: What timeline can we expect for Admelog’s full approval? What is the nature of the patent issues? How do they compare with the ongoing Merck/Sanofi lawsuit over patent infringement of Lantus (insulin glargine)?

Q: What has the response been like to Insulin lispro Sanofi in Europe since EMA approval in July? How are HCPs, patients, and payers approaching the first-to-market biosimilar mealtime insulin?

Q: How will Sanofi prioritize basal insulin Lantus, rapid-acting insulin Apidra, and new biosimilar insulin Admelog? Apidra has never quite taken-off commercially. The product consistently captures only a single-digit share of the rapid-acting market by value, far behind Lilly’s Humalog and Novo Nordisk’s NovoRapid. Could Admelog boost Sanofi’s share in this class?

Q: How will Admelog affect the dynamics of the rapid-acting insulin market? Whole class sales have been sluggish (up 1% YOY to $1.6 billion in 2Q17), due in part to competitive pressure from GLP-1 agonists and SGLT-2 inhibitors (both address postprandial glucose excursions) as well as an extremely competitive pricing environment in the US. As a lower-cost option, could Sanofi’s biosimilar insulin lispro circumvent both these challenges?

-- by Payal Marathe and Kelly Close