FDA Backs Novartis MS Pill Mayzent With Broad Label
Executive Summary
Mayzent is the first oral therapy proven to delay progression in patients with secondary progressive multiple sclerosis and Novartis pharma chief Paul Hudson tells Scrip its $88,500 list price will not affect access.
Novartis AG has won FDA approval for its eagerly anticipated multiple sclerosis drug Mayzent and won big, with the agency granting the green light for the therapy to be used across the spectrum for patients with relapsing forms of the neurological disease.
The thumbs-up from the FDA means that Mayzent (siponimod) is now the first oral treatment specifically indicated for active secondary progressive multiple sclerosis (SPMS) in adults. This was expected but the approval also states that the label on the drug, an improved version of Novartis' older therapy Gilenya (fingolimod), includes clinically isolated syndrome (CIS), defined as a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination in the central nervous system, as well as relapsing-remitting MS.
In an interview with Scrip hours after the FDA approval was revealed, Novartis head of pharmaceuticals Paul Hudson said that when Mayzent is made available in the US in the next week, the emphasis will be very much on SPMS patients. Specifically, he spoke of those patients "who have had 10-15 years of the disease and face the 'heart sink moment' of sitting in front of their neurologist and they both know things are getting worse, though they can't always pinpoint a relapse."
However, the patient "knows they're struggling and the physician is desperate not to call it as SPMS because they have no medical treatment. However, we've reached the moment where now they do," Hudson added. He went on to say that Mayzent is "going to be fantastic for patients in trying to stop that descent into lack of mobility and preserving cognition, perhaps even bladder function, really terrible lifestyle-impacting burdens."
Hudson said that the principal aim was to get SPMS "properly characterized in the label" and "payers and providers want the confidence that comes from that and that's what we got." However Novartis got "slightly wider and we have to be responsible with that but there is a large group of progressive patients who start much earlier and that's why the wider label will give some physicians pause for thought about trying to address progression much earlier."
The approval of Mayzent, which selectively binds to the S1P1 and S1P5 receptors. is based on the Phase III EXPAND study in SPMS patients who had a mean age of 48 and had been living with MS for approximately 16 years. More than 50% had a median expanded disability status scale (EDSS) score of 6.0 and relied on a walking aid.
The drug significantly reduced the risk of three- and six-month confirmed disability progression, by 21% versus placebo, and favorable outcomes in other relevant measures of MS disease activity.
However, Hudson noted that while the patients in EXPAND had an EDSS of 6.0, there is data down to EDDS2, "which means that if you've got somebody who is progressing between relapses, you may say to yourself, what's the best treatment option here…we were encouraged by the regulator's opinion that there is a wider remit [and] if a physician wants to go earlier, they have the label." Still, he stressed that at least in the first year or so from launch, SPMS "is where our energy will go."
The list price for Mayzent is $88,500 per year, considerably lower than Gilenya ($98,500) and less than Biogen Inc.'s RRMS pill Tecfidera (dimethyl fumarate) which costs $93,700 at list price, according to Credit Suisse. Hudson told Scrip that "we have priced it at the lower end of the orals because we want the physician to make a clinical decision and not be encumbered by a price discussion."
He added that obviously "much depends on our relationship with the pharmacy benefit managers and the progress we can make with them on access, but I feel confident that that at least from a list price perspective, we have removed any burden." Novartis is also putting together programs to help those patients who will have problems affording Mayzent.
Hudson claimed that "Novartis is probably the best company in the world in neuroscience and we have produced unique data," noting that Biogen's Tysabri (natalizumab) failed in the SPMS patient population. He concluded by saying that Mayzent, which is widely expected to be a blockbuster, is the first of three expected US approvals for the firm this year (a European okay is forecast before the end of 2019), to be potentially followed by the gene therapy Zolgensma for spinal muscular atrophy and the ophthalmology treatment brolucizumab.
Surprising Breadth
The breadth of label granted to Mayzent surprised analysts. In an investor note, Jefferies noted that the broad label, plus the unmet medical need of SPMS and "much less onerous first-dose monitoring requirements" could see the drug bring in worldwide peak sales of $1.25bn. The SPMS indication should be the main driver but it is a sizable one; around a quarter of the RRMS patients will transition to SPMS within 10 years, the broker noted, and over 75% will transition to SPMS after 30 years. It is estimated that at any one time around 30% of MS patients have SPMS.
Credit Suisse analysts said the ‘in transition’ patients represent "an additional early opportunity on top of our expectations…and we expect the company will focus on Mayzent’s unique positioning in active SPMS and late-stage RRMS." As for the early MS marketplace, they noted that "this is a highly competitive area, increasingly dominated" by Roche's game-changing infusion Ocrevus (ocrelizumab) "and where Mayzent has limited differentiation and only modest clinical data."
The approval, for which Novartis used a priority review voucher for the filing with the FDA, boosts the company's strong MS franchise. Gilenya is the company’s biggest seller, with sales last year of $3.34bn and the company's CEO Vas Narasimhan told Scrip in January that while the legal situation around the drug's patents was "extraordinarily complicated," with several generics firms threatening at-risk launches, the company expects no copycat versions to hit the market this year. (Also see "Carry On Cosentyx As Novartis Lines Up More Blockbusters " - Scrip, 30 Jan, 2019.) (Also see "US Court of Appeals Upholds Gilenya Compound Patent, Dealing A Blow To Ezra Ventures" - Generics Bulletin, 11 Dec, 2018.)
Nevertheless, Gilenya generics are not that far away and the already-crowded MS market in the US can expect to see a few more entries in the next couple of years. In particular, Novartis will be keeping a close eye on Celgene Corp.'s ozanimod, which was re-filed with the FDA earlier this week and Johnson & Johnson's ponesimod, which is forecast to get regulatory approval late 2020. (Also see "Celgene Joins Troubled MS Club With Refuse To File For Ozanimod From US FDA" - Pink Sheet, 28 Feb, 2018.)