Sanofi Forced to Defend Lantus' Safety Again

June 18, 2010 Sanofi forced to defend Lantus' safety again

Evaluate Vantage

Reports that your most valuable product could increase the risk of cancer would put any company on the back foot. This is the position Sanofi-Aventis found itself in today following fresh allegations that its long-acting insulin, Lantus, the world’s biggest selling single insulin product, increased the risk of cancer in diabetics.

Shares in the French healthcare giant fell as much as 7% in early trading today to €47.61 before recovering gradually as the company and multiple analysts tried to downplay the significance of a new Italian study published in the Diabetes Care journal. Those sensing déjà vu will remember similarly damaging studies in Diabetologia exactly 12 months ago (Sanofi brought low by Lantus cancer rumours, June 26, 2009). The Diabetologia studies have since been largely discredited and Lantus prescriptions were not materially affected (see table below). Nevertheless, Sanofi now has another major PR job on its hands to protect Lantus from increasing competition from insulin giant, Novo Nordisk. The American Diabetes Association (ADA) conference next week is warming up nicely.

Valuable analysis?

A group of Florence-based researchers studied the records of 1,500 diabetics going back six years and focused on the possible reasons why 112 of them developed cancer. A criticism of similar analysis showing Lantus to be perfectly safe has been that patients were only monitored for a short time so this six year period is important, given the time it takes for cancer to develop.

Taking into account mitigating factors such as co-morbidity, dose and length of treatment, the results suggest a statistically significant 3.7x increase risk of cancer in patients receiving a high dose of Lantus.

The researchers concluded that: “dosages (of insulin) should always be considered when assessing the possible association of insulin and its analogues with cancer”.

As to the merits of these kinds of retrospective studies, as opposed to prospective randomised controlled trials, a similar debate has started to that held a year ago. Naturally, Sanofi was quick to try and diffuse the situation, maintaining its line that it is almost impossible to draw any firm conclusions from these types of studies.

Many analysts are also of this view and point to upcoming presentations at ADA, of similar retrospective studies as well as interim safety data from the large Origin trial, which will support the safety of Lantus.

Valuable franchise

Nevertheless, this new study will be of concern to Sanofi and doctors alike and prescription rates over the coming months will be subject to severe scrutiny once more.

Although the impact of the Diabetologia studies a year ago was perceived to be minimal, archive forecast data below from EvaluatePharma reveals a 7% decline in sales for 2014 in the last 12 months, a reduction of a decent $437m to $6.21bn. WW annual sales ($m)

Product Company Archive Date 2009 2010 2012 2014

Lantus Sanofi-Aventis May 2010 4,293 4,807 5,738 6,209

May 2009 4,365 4,900 5,993 6,646

difference ($m) (72) (93) (256) (437)

% difference -2% -2% -4% -7%

Levemir Novo Nordisk May 2010 978 1,270 1,850 2,380

May 2009 973 1,190 1,567 2,072

difference ($m) +5 +79 +284 +308

% difference +0% +7% +18% +15%

Whether this new study means forecasts are reduced further remains to be seen. Bernstein Research analysts wrote today that they believe the study was better designed and analysed than the Diabetologia studies, suggesting that the cancer link to high doses of Lantus is “plausible”.

The Bernstein analysts also see this as a positive for Novo Nordisk, particularly with regard to its own long- acting insulin, Levemir. The table above certainly suggests the Novo product could have benefitted from the Lantus cancer scare story last year; sales in 2014 have increased 15% to $2.38bn.

As well as Levemir, there are high expectations over Novo’s next generation insulin product, degludec, which is designed to significantly reduce the hypoglycaemia risk associated with Lantus. Again, presentations of clinical data at ADA for degludec are expected to be keenly attended.

Novo’s shares gained 4% today to a new record high of DKr508, valuing the company at around $45bn; that is a market capitalisation similar to Bristol-Myers Squibb and higher than Eli Lilly. While the Lantus safety scare could be positive for Novo, the major development setback to Roche and Ipsen’s taspoglutide is also a major boon for the Danish group, delaying a major competitor to Victoza (Roche's diabetes blow prompts Amylin gain, June 18, 2010).

As the table below shows, Novo already dominates the insulin market, capturing 47% of the $14bn market last year. This share is only expected to grow further to 56% by 2016, helped by Levemir and degludec. The Lantus cancer safety scare could only serve to boost Novo’s dominance of the insulin market even further. WW Insulin Market WW annual sales ($m)

CAGR Rank Product Generic Name Company Status 2009 2016 (09- 16)

Sanofi- 1 Lantus insulin glargine Marketed 4,293 4,673 1% Aventis

Novo 2 NovoRapid/NovoLog insulin aspart Marketed 1,825 3,371 9% Nordisk

Novo 3 Levemir insulin detemir Marketed 978 2,738 16% Nordisk

Human insulin Novo 4 insulin (human) Marketed 2,504 2,048 (3%) & devices Nordisk

insulin & insulin Novo 5 NovoMix Marketed 1,216 1,909 7% aspart Nordisk

6 Humalog insulin lispro Eli Lilly Marketed 1,959 1,696 (2%)

7 Humulin R insulin (human) Eli Lilly Marketed 1,022 1,014 (0%)

Sanofi- 8 Apidra insulin glulisine Marketed 191 497 15% Aventis

insulin degludec (+ Novo 9 Degludec/DegludecPlus Phase III - 328 n/a insulin aspart) Nordisk

10 Afrezza insulin MannKind Filed - 223 n/a

Other products 37 218

Total Insulin Market 14,025 18,715 4 %

Novo Nordisk market share 47% 56%