There were times when it might have looked easier for Sanofi to give up on Lemtrada, its seemingly jinxed multiple sclerosis treatment, which it had struggled to launch in a rapidly changing US market. But the French group’s perseverance has paid off and after more than two years of asking Lemtrada finally got a green light to US approval on Saturday.
But with a strict label, onerous ongoing testing of patients and a designation for use in only third or fourth line, it will be an uphill battle for Sanofi to carve out sales in a space that has been all but conquered by less troubled oral treatments such as Biogen’s Tecfidera. Indeed, forecasts from EvaluatePharma show that Lemtrada will only just limp into the top 10 MS treatments by 2020 (see table below).
|Top 10 MS drugs in 2020|
|Tecfidera||Biogen Idec||Nrf2 pathway activator||876||6,435||Marketed|
|Gilenya||Novartis||S1P receptor modulator||1,934||2,973||Marketed|
|Tysabri||Biogen Idec||Anti-VLA-4 MAb||1,413||2,600||Marketed|
|Avonex||Biogen Idec||Interferon beta||3,005||1,885||Marketed|
|Rebif||Merck KGaA||Interferon beta||2,477||1,395||Marketed|
|Aubagio||Sanofi||PDGF tyrosine kinase & DHODH inhibitor||221||1,214||Marketed|
|Ampyra||Acorda Therapeutics||Potassium channel blocker||303||810||Marketed|
|Plegridy||Biogen Idec||Interferon beta||-||697||Approved|
Of the various potential brakes on runaway sales, perhaps the most serious is the safety profile and toxicity of Lemtrada. This has left the Sanofi drug with boxed warnings of potentially fatal autoimmune reactions and an increased risk of cancer. There is also a requirement for patients to undergo regular blood and urine testing for idiopathic thrombocytopenic purpura and overactive thyroid gland.
As such it is no wonder that rather than leaping to the front of the treatment queue, Lemtrada is recommended only for patients who have failed on at least two other treatments.
Look on the bright side
Those trying to put more of a positive spin on the prospects for Sanofi’s second US-approved MS drug have pointed to the fact that the anti-CD52 MAb offers an alternative treatment method for a large population, so in theory it could suit some highly refractory patients.
They also comment on Lemtrada’s interesting infusion administration route, whereby the first dose is given daily for five consecutive days and the second a year later over three consecutive days.
While this might sound more convenient than some of the other infusion treatments, it is still less convenient than swallowing a pill and there is also the important matter of pretreating patients with high doses of steroids and two months of prophylactic antivirals for herpes.
Perhaps the biggest indicator of how dimly most investors view Lemtrada’s prospects is that, while some analysts had removed the drug from their models, others were at best only expecting a 50% chance of success, so in theory approval should have provided Sanofi with a much needed share price boost. Instead by late afternoon the shares were barely up 1%, trading at €75.09.
Historically Lemtrada has not had an easy time of it. In August 2012 the FDA refused to file its NDA submission. Then came a complete response letter in December 2013, despite a positive advisory committee, again owing to concerns over trial design and data. Having resubmitted data packages, rather than repeating costly phase III trials, Sanofi has finally made it.
But with consensus sales of only $728m in 2020, Lemtrada is set to be one of the also-rans of the MS market, justifying the heavy contingent value rights Sanofi embedded in the contract as part of its $20bn acquisition of Genzyme back in 2011.
Having missed the deadline to get the drug approved in April, the main payout for the CVRs is now annualised Lemtrada sales above $400m. Unfortunately, the $400m needs to be hit in the four calendar quarters immediately following Lemtrada’s first sale and, according to EvaluatePharma consensus, revenues are not expected to top $400m before 2017.
So what can Sanofi claim from the money it has spent on Lemtrada? At best it can now say it has a complete MS franchise with Lemtrada and Aubagio serving both ends of the market. At worst it has a niche product that is unlikely to return the investment spent on it.