Eoneren
Getting a brand new drug throughout the end line to FDA approval is troublesome sufficient in its personal proper – over 90% of medication that enter into Part I testing by no means make it – however approval is only one hyperlink in a series of challenges. No drug sells itself or pays for itself, and it takes money and time to not solely make medical doctors conscious of the drug and motivated to make use of it, but additionally to get payors to reimburse for it.
Whereas Lexicon Prescribed drugs (NASDAQ:LXRX) has managed to get two medicine onto the market, the launch of its most up-to-date medical success, Inpefa, has proceeded at a slower tempo than even I’d hoped to see (and I’ve lengthy been fairly skeptical of the actual income potential of the drug). Greater than a 12 months on into the launch of the drug, there’s some proof of constructive momentum, however there’s lots of work left to do, and the shares are down about 30% since my final replace.
New management and a good pile of money provides Lexicon one other probability to vary the narrative. Inpefa is an efficient drug that targets an actual downside and one that’s at the moment under-treated. Likewise, there are legitimate business alternatives for sotagliflozin (the generic identify of Inpefa) in Kind 1 diabetes (and probably hypertrophic cardiomyopathy as nicely) and LX9211 in diabetic peripheral neuropathy. All of that being mentioned, success is way from assured.
One other Quarterly Miss Doesn’t Assist The Story
Across the time that Lexicon first launched Inpefa, I commented that it wouldn’t actually be truthful to guage the success of the launch by the primary few quarters – there was merely an excessive amount of work for the corporate to do, together with working with payors, to anticipate a steep gross sales ramp for a drug that was coming into a market that already had well-established options.
And so it has been, with Inpefa gross sales falling chronically in need of initially analyst expectations. For the second quarter, Lexicon introduced $1.6M in gross sales of Inpefa. That was up 47% sequentially, however over one million in need of analyst expectations (which ranged from $1.8M to $3.4M).
Trying on the chart supplied for the convention name, Lexicon appears to be doing higher than I’d anticipated when it comes to prescription quantity (over 4,000 in Q2) and implied quantity market share, but it surely seems to be as if the corporate is providing a extra sizable low cost to payors to drive prescriptions. Administration did point out that fee protection is as much as 48% and that packages meant to enhance entry and protection stay ongoing.
This stays a difficult business alternative. The brand new CEO, who got here to Lexicon after main the cardiometabolic enterprise at Novartis (NVS), might have information concepts round technique and business execution that may drive an inflection in adoption, however for now my thesis on Inpefa seems to be enjoying out – it’s a laggard to rivals like AstraZeneca’s (AZN) Farxiga and Lilly (LLY)/Boehringer Ingelheim’s Jardiance and for no matter efficacy superiority traders need to attempt to tease out of the medical information, it’s going to be an extended, onerous, and costly street to construct Inpefa to significant real-world income.
Will The FDA Lastly Approve Zynquista?
After an extended means of wrangling with the FDA, the corporate was lastly in a position to resubmit its software for Zynquista (additionally sotagliflozin) to the FDA and the company has given it a December 20 PDUFA date. Administration believes an AdComm assembly is probably going, and that may give Lexicon administration the chance to make its case that the FDA’s considerations across the security of Zynquista (primarily associated to diabetic ketoacidosis, or DKA, and notably throughout sleep) are overblown and might be managed/mitigated by sufferers.
My opinion has all the time been that the FDA was too cussed about Zynquista and the proposed threat management technique, however I additionally respect that the FDA has taken a number of black eyes over time from diabetes medicine that it accepted and had been later discovered to have significant security dangers. In any case, I do suppose there’s a want and a business alternative for drugs that may assist folks with Kind 1 diabetes higher handle their illness.
I think about it a toss-up at this level as as to if the FDA will approve the drug. The efficacy is there, and I feel the chance of DKA might be managed, however the panel might take a extra cautious view on security and threat/profit, giving the company the chance to take cowl behind an hostile AdComm suggestion and as soon as once more reject the applying.
Ought to FDA approval come, advertising the drug will nonetheless be a problem. Some retail traders appear to love to consider that medicine simply promote themselves, as if there’s a little bit holographic pop-up on the bottle that particulars all the medical advantages, or that physicians who typically barely have time to see sufferers and get their notes/charting finished will spend hours each night poring over the newest medical publications to remain updated on all obtainable remedy choices for his or her sufferers.
That’s not the case, and whereas Lexicon administration is true that the endocrinologist inhabitants is comparatively concentrated, the truth is that solely about half of sufferers with Kind 1 diabetes see an endocrinologist. That can possible restrict the market alternative for Zynquista to some extent, at the least initially, although I might hope there’s a bigger skew of individuals with Kind 1 diabetes and power kidney illness (the goal inhabitants for the drug) who see an endocrinologist.
Pipeline Worth Is Nonetheless Current
Along with the commercialization of Inpefa and the potential approval and commercialization of Zynquista, Lexicon has one other shot on aim with its sotagliflozin franchise. Administration is enrolling sufferers within the Part III SONATA examine of sotagliflozin in hypertrophic cardiomyopathy, and if this trial is profitable (information is anticipated late in 2026 or early in 2027), one other significant market may into play.
How significant the chance is stays to be seen. Whereas 1M or extra folks within the U.S. are thought to have hypertrophic cardiomyopathy, solely round one-quarter to one-half of them ever present signs. Nonetheless, the situation might be fairly critical for many who are symptomatic, so significant enchancment in metrics just like the Kansas Metropolis Cardiomyopathy Questionnaire (or KCCQ) may nonetheless be commercially related.
Past this, Lexicon nonetheless has the PROGRESS Part IIb examine of LX9211 in diabetic peripheral neuropathy, with a readout anticipated in Q2’25. I nonetheless think about this a toss-up given earlier trial outcomes, however success may drive over $600M in annual income potential.
Lexicon can also be in preclinical improvement for LX9851, an ACSL5 inhibitor for weight problems. ACLS5 is expressed in liver, intestinal, and adipose tissue and performs a key function in lipid metabolism. Primarily based on the mechanism of motion, this may very well be an fascinating drug candidate for weight problems and/or fatty liver illness (metabolic dysfunction-associated steatohepatitis). Bear in mind, although, that as a preclinical candidate, there’s an extended solution to go earlier than there’s helpful and significant information in people to contemplate.
The Outlook
I’ve revised my mannequin for Inpefa based mostly upon what I’m seeing when it comes to prescription quantity development and realized pricing (specifically, what seems to be like a decrease efficient value than I’d anticipated). I’m now on the lookout for lower than $400M in income from the drug, which is admittedly very low relative to the entire addressable market alternative, however I have to see extra proof of sustainable income right here earlier than getting extra bullish. Plans to enhance entry and protection ought to drive some acceleration within the second half, however we’re nonetheless speaking a few drug that’s actually annualizing at below $10M at this level.
That change takes my truthful worth from a little bit over $6/share to a little bit below $5/share, with a fairly even break up throughout the alternatives in coronary heart failure (Inpefa) and Kind 1 diabetes (Zynquista) at $1.50/share, and diabetic neuropathy (LX9211) and sotagliflozin in hypertrophic cardiomyopathy at $1/share. In each considered one of these circumstances there’s the chance for incremental upside, and maybe substantial upside, based mostly upon improved medical execution (Inpefa) or constructive regulatory/medical updates.
The Backside Line
Whereas I’m nonetheless fairly bearish on the business alternative for Inpefa, there’s a new administration staff in place and a money stability that ought to fund at the least six extra quarters of market and medical improvement – time sufficient, at the least, to see if new methods unlock extra quantity in coronary heart failure, if the FDA will approve Zynquista, and if there’s an actual future for LX9211. That’s sufficient to maintain me for now, however it is a identify appropriate just for traders who can settle for excessive ranges of threat.