Analysis focus: ESPR
Esperion Therapeutics (NASDAQ:ESPR) key attraction is that the market that its lead candidate targets – LDL-C reduction – once had Lipitor, a drug that generated $13bn at peak for Pfizer (NYSE:PFE). The difference is that Lipitor and a number of similar drugs are statins, and there is a sizeable statin-intolerant patient population who do not have a way to use these drugs. A 2008 British Journal of Cardiology paper said that between 5-10% of patients are statin intolerant, and the number may well be an underestimation. This, then, is the target market of bempedoic acid, ESPRs lead drug candidate which has shown some outstanding data till date. In a trial we covered in July last year, patients showed a 27.8% reduction in LDL-C compared to placebo – use of placebo being justified because the drug candidate is not competing against Lipitor or other statins.
The problem with bempedoic acid is that it directly competes with PCSK9 inhibitors, approved products like Repatha and Praluent – and their sales have not been as impressive as once assumed. Bempedoic acid, though not as efficient at reducing LDL-C as these drugs, may be priced cheaper – Repatha costs around $14000 per year. Also, another claimed edge is that bempedoic acid reduces high sensitivity C-reactive protein or hsCRP, which is a biomarker or sorts for CV diseases. In a recent phase 2 trial, hsCRP was reduced 34% compared to 2% in placebo.
Yesterday, NASDAQ suspended trading in ESPR pending release of news. The news, which came out later, showed that bempedoic acid was successful in the third of five pivotal Phase 3 studies (Study 3 or 1002-046). A specific subgroup of patients – those with High-risk of atherosclerotic cardiovascular disease (ASCVD) or at high-risk for ASCVD with hypercholesterolemia (elevated blood cholesterol) inadequately controlled with maximally tolerated background therapy – saw 23% decrease in bad cholesterol compared to 1% in placebo after 12 weeks of treatment. The study thus met the primary endpoint of demonstrating a statistically significant reduction in LDL-C versus placebo at week 12. Even at week 24, those percentages were 26 and 2 respectively, showing sustained treatment effect over longer periods.
In some secondary measures, as well, bempedoic acid showed strong improvement. For example, there was a 25% reduction in C-reactive protein, an inflammation biomarker, compared to an increase of 3% for control (p<0.001).
The next important milestone for the company is data release for its combo trial with ezetimibe, which is a generic drug Merck once sold as Zetia. The company should file for an NDA sometime next year, and given that an FDA-mandated CV study is already underway, chances of approval are decent. Liver issues are a worry – there have been a number of deaths in the trial but it is not known whether they are treatment emergent. But some analysts consider this a non-issue given that statin has worse liver toxicity issues; they assume the deaths are unrelated to the drug. However, 13 deaths in the treatment group compared to 2 in the control rightly spooked investors earlier this month, taking the stock down. A lot more research needs to be done with these deaths before we can be more confident of ESPRs prospects.
Stocks in News: Analysis of CMTA, INSM
Clementia Pharma’s palovarotene shows positive effect in mid-stage FOP study
Discussion: Small cap Clementia Pharmaceuticals (NASDAQ:CMTA) announced its interim results from a Phase 2 clinical trial evaluating palovarotene in patients with fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder in which muscle and connective tissue are gradually replaced by bone. Palovarotene, a small molecule retinoic acid receptor gamma agonist, reduced new bone growths at flare-up sites by 91% at week 12 compared to placebo and untreated flare-up sites from the company’s natural history study. NWith no new bone growths at week 12 in sample group of patients at month 12, signalled a sustained benefit. RFurther recruitments isare ongoing on for a Phase 3 study and the first data readout of that study should happen in mid-2019. FOP is an extremely rare but fatal disease affecting approximately 1 in 2 million people. However, it has attracted received sustained attention as the microcosm of close to 30M people in the U.S. affected by a rare disease.
Insmed (NASDAQ:INSM) is down in spite of positive Phase 3 data
Discussion: Result of a Phase 3 clinical trial assessing Insmeds (INSM) ALIS (amikacin liposome inhalation suspension) in adult patients with treatment-resistant nontuberculous mycobacterial (NTM) lung disease has been published. DataIt shows that NTM caused by Mycobacterium avium complex (NYSE:MAC) show significant improvement from 9% (out of a patient base of 336) that received guideline based therapy (NASDAQ:GBT) to 29% that received GBT + ALIS and this result has also met the primary endpoint. PDUFA Actions date for the companys marketing application under FDA review is 28 September. There is a steady rise in rate of report of NTM across various regions of the U.S. (3.6~8.8/ M) and thus has an expanding patient base.
In other news:
Mercks (NYSE:MRK) KEYTRUDA (pembrolizumab)) + chemo showed significant treatment benefit in its Phase 3 KEYNOTE-407 study. An interim analysis by the Data Monitoring Committee has shown significant increase in OS (overall survival) and PFS (progression-free survival) in first-line metastatic squamous non-small cell lung cancer (sNSCLC).
A Los Angeles jury has given a $21.7M verdict against Johnson & Johnson (NYSE:JNJ) and its talc suppliers in a case where a woman alleged that exposure to asbestos in JNJs baby powder has caused her mesothelioma, a form of cancer.
Avinger (NASDAQ:AVGR) received 510(k) clearance from the FDA for its planned launch of next generation Pantheris Lumivascular atherectomy system, the first-ever image-guided atherectomy device for the treatment of peripheral artery disease (PAD).
TherapeuticsMD (NYSEMKT:TXMD) trading was suspended by NASDAQ pending release of FDA communication regarding TX-004HR. PDUFA is May 29. The company update says it has received no FDA communique.
Leerink Revelation Partners and Industry Ventures has acquired ~9.4 M shares of AcelRx Pharmaceuticals (ACRX) previously manaaged by Three Arch Partners.
Vifor Fresenius Medical Care Renal Pharma Ltd. has agreed to commercialize KORSUVA (difelikefalin) for the treatment of chronic kidney disease-associated pruritis in dialysis patients developed by Cara Therapeutics (NASDAQ:CARA) outside the US, Japan and South Korea. CARA will receive $50mn upfront, up to $30M in regulatory miliestones, up to $440M in commercial milestones and tiered royalties on net sales. Vifor Fresenius will also make a $20M equity investment in Cara at ~$17/share.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
Editor’s Note: This article covers one or more stocks trading at less than $1 per share and/or with less than a $100 million market cap. Please be aware of the risks associated with these stocks.