Kerrisdale on iRhythm Technologies

iRhythm faces reimbursement cuts of 30-60% in the near future.

iRhythm faces formidable competition that it has (over)confidently dismissed.

The TAM for the Zio is much smaller than iRhythm suggests, and the effort to expand its product offering through the Zio AT has been a failure.

We are short shares of iRhythm Technologies (IRTC), a $2.3bn medical device company trading at over 15x sales despite facing multiple factors that will dramatically cut its revenue growth in the coming years. iRhythm’s Zio, developed over a decade ago and accounting for nearly all the company’s $150m in sales, is a one-lead heart rate monitor in patch form. This “extended Holter monitor” is worn by patients for up to 14 days, during which the device continuously records heart rhythm data. Each application of a Zio patch costs payors about two to four times what it would cost to use legacy monitoring modalities, but iRhythm claims that the Zio reduces costs for the healthcare system through increased effectiveness and better patient compliance.

A closer look at the circumstances surrounding the reimbursement treatment of the Zio Patch reveals that at the core of iRhythm’s revenue base is an exceedingly generous, but increasingly fragile, reimbursement regime. The Zio patch’s success in achieving unit-level revenues greater than any other cardiac monitoring method is a function of iRhythm’s subtle and skillful maneuvering around the arcane technicalities at the center of the American Medical Association’s reimbursement coding process. This has allowed iRhythm to essentially “name its own price” in the Medicare negotiation process, leading to unduly favorable reimbursement from commercial payors as well.

But the price gouging will inevitably be short-lived. The rapid increase in Zio patch utilization has now put a bullseye on its back, increasing the odds that both Medicare and commercial payors will both cut back on reimbursement levels and throttle utilization. In addition, the Zio patch is currently reimbursed under a temporary CPT tracking code that we expect will be transitioned into a permanent code for calendar year 2021. In the process, we anticipate reimbursement levels for the Zio patch will fall by over a third and potentially more than 50%. …

https://seekingalpha.com/article/4248365-irhythm-technologies-inc-growth-reversal-will-leave-investors-heartbroken

Esperion’s cholesterol-lowering pill works when statins fail

A cholesterol lowering daily pill from US pharma Esperion, which can be used when statins are not working in high-risk patients, is edging closer to the market after a phase 3 trial success.

The trial showed bempedoic acid significantly lowered “bad” LDL-cholesterol, and reduced the inflammation biomarker high-sensitivity C-reactive protein in high-risk patients with high LDL cholesterol levels, despite taking medication such as statins.

Esperion’s international Study 1 tested the drug versus placebo in 2,230 high-risk patients with atherosclerotic cardiovascular disease (ASCVD) that was inadequately controlled with lipid-modifying therapies, including maximum doses of statins.

The company has already filed bempedoic acid, and a combination pill with ezetimibe, with the FDA and European Medicines Agency.

If approved, the drug could be a strong competitor to Sanofi and Amgen, whose injected PCSK9 inhibitor drugs Praluent  and Repatha are used in patients with high cholesterol levels despite statin therapy.

The study involved patients with ASCVD or heterozygous familial hypercholesterolemia with high LDL-C levels, inadequately controlled with lipid-modifying therapies including maximum dose statins.

They were randomly selected in a 2:1 ratio to receive bempedoic acid or placebo, with the main goal being safety and tolerability after a year of therapy.

The secondary objective assessed efficacy of bempedoic acid at lowering cholesterol after 12 weeks versus placebo.

Tertiary objectives were to assess the effect of bempedoic acid on other lipid parameters and risk markers, including hsCRP.

Results published in the New England Journal of Medicine showed that after 12 weeks bempedoic acid significantly lowered LDL-cholesterol by 18% compared with background maximally tolerated statin therapy.

It significantly reduced high-sensitivity C-reactive protein by 22%, which is an important marker of underlying inflammation associated with cardiovascular disease.

The drug did not lead to higher overall adverse events compared with placebo (78.5% versus 78.7% with placebo) and the proportion of patients with serious adverse events was similar (14.5% versus placebo 14%).

There were fewer adjudicated major adverse cardiac events (4.6% vs placebo 5.7%), and lower rates of new onset or worsening of diabetes (3.3% versus 5.4% placebo).

Esperion is also waiting for results from the CLEAR OUTCOMES trial, which is testing longer-term safety and whether the treatment reduced cardiovascular disease risk in addition to lowering cholesterol.

Professor Kausik Ray, from the Imperial Centre for Cardiovascular Disease Prevention, at Imperial College London’s School of Public Health, said: “This latest study shows that bempedoic acid could be another addition to the arsenal of once-daily, oral cholesterol-lowering treatments available to patients.

“Overall, these recent studies show that not only is the treatment generally well-tolerated, being comparable with placebo, and potentially safe over longer periods, but that when added to high intensity statin treatment it can help to further reduce LDL-cholesterol levels.”

https://pharmaphorum.com/news/esperions-cholesterol-lowering-pill-works-when-statins-fail/

Kitov to Acquire Clinical Stage Candidate for Immuno-Oncology Transformation

-Transaction adds immune oncology candidate to Kitov’s pipeline which includes promising NT-219 cancer drug resistance prevention therapeutic candidate

– Kitov to receive $3.5M investment from prominent life science funds Orbimed, Pontifax, and Arkin Holdings, each becoming a principal shareholder

– Kitov plans to initiate Phase I/II study with CM-24 in early 2020

Kitov Pharma(NASDAQ/TASE: KTOV), an innovative pharmaceutical company, today announced it has signed an agreement to acquire FameWave Ltd., a privately held biopharmaceutical company developing CM-24, a clinical stage monoclonal antibody targeting CEACAM1, a novel immune checkpoint. Kitov is planning initiation of a Phase I/II study in early 2020 to evaluate the safety and efficacy of CM-24 in combination with an anti PD-1 inhibitor. Kitov to host a conference call to discuss the transaction. The scheduling of the call will be announced separately.

“Combining this transaction with our proprietary NT219 program, Kitov will become a clinical stage oncology company backed by the support of leading global life science funds. With the NT219 and CM-24 oncology candidates, we are opening an exciting future for Kitov and I’m looking forward to building on this momentum. We are very pleased that the investment and support of three leading global life science funds will enable Kitov to advance our clinical programs and expand our institutional investor base,” stated Kitov CEO, Isaac Israel.

https://www.marketscreener.com/KITOV-PHARMA-LTD-10619522/news/Kitov-Pharma-to-Acquire-Clinical-Stage-Candidate-CM-24-Creating-a-Transformational-Immuno-Oncology-28164995/

Regeneron, Sanofi to Present New Praluent Data at Cardio Conference

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that four new sub-analyses from the Praluent (alirocumab) ODYSSEY OUTCOMES cardiovascular (CV) outcomes trial will be presented at the American College of Cardiology’s 68th Annual Scientific Session (ACC.19), held March 16-18, in New Orleans, LA.

The sub-analyses from the 18,924-patient ODYSSEY OUTCOMES trial include: A Featured Clinical Research presentation that evaluates the impact of lowering lipoprotein(a) [Lp(a)] with Praluent on total CV events, independent of low-density lipoprotein cholesterol (LDL-C) reduction. Elevated Lp(a), an inherited lipid disorder, is associated with increased risk of atherosclerosis and CV disease.

An oral presentation that shows Praluent treatment was associated with larger reductions in the risk of major adverse CV events (MACE) and death in patients with polyvascular disease, compared to those without. Polyvascular disease is defined as having an acute coronary syndrome (ACS), plus either concurrent peripheral artery disease or cerebrovascular disease, or both.

Regeneron and Sanofi presentations at ACC.19 from the ODYSSEY clinical trial program and other trials include the following three oral presentations and five poster presentations.

https://www.marketscreener.com/REGENERON-PHARMACEUTICALS-10649/news/Regeneron-Pharmaceuticals-and-Sanofi-to-Present-New-Praluent-Data-at-ACC-19-28164387/

Novartis generics boss quits amid conjecture over business’s future

Novartis’s generics chief is quitting after the Swiss drugmaker sold parts of the business and initiated an 18-month revamp, fueling speculation about an eventual spin-off or sale.

Richard Francis, Sandoz’s boss since 2014, is stepping down, Novartis Chief Executive Vas Narasimhan said on Thursday, adding “Richard has decided that for personal reasons he cannot commit to stay with Sandoz until the transformation is completed”.

Francesco Balestrieri, head of Sandoz’s Europe region, will become interim CEO to oversee what Narasimhan called “a multi-year transformation program” in which Sandoz re-focuses on biosimilars — copies of patent-expired biological drugs made by rivals — and hard-to-make generics like insulin.

Balestrieri, at Novartis for 25 years, assumes control over a division with nearly $10 billion in annual sales.

Sandoz last year sold a U.S. pills and dermatology portfolio to India’s Aurobindo and embarked on a “de-integration” of Francis’s division from the rest of Novartis, a process Narasimhan said will stretch into 2020 and clear the way for talks about the business’s future.

Narasimhan has been remaking Novartis by buying speciality treatments like nuclear medicine for cancer and gene therapy, while jettisoning an over-the-counter drugs business and eye surgery-and-contact lens division Alcon, due to be spun off as early as next month.

The departure of Francis, a British citizen, does nothing to quiet conjecture about Sandoz’s future within Novartis, analysts said.

“We see our assumption confirmed that in the next 12 to 18 months a definitive decision may come about whether the generic unit will remain within Novartis,” said Zuercher Kantonalbank analyst Michael Nawrath.

“Even though the Novartis chairman said recently Sandoz isn’t for sale for now, a spin-off like they’re doing with Alcon would align with the strategy of becoming a focused, pure-play drugmaker.”

https://www.marketscreener.com/NOVARTIS-9364983/news/Novartis-generics-boss-quits-amid-conjecture-over-business-s-future-28162912/

KalVista Pharmaceuticals Reports Fiscal Third Quarter Results

• Oral Hereditary Angioedema (HAE) Candidate KVD900 Phase 2 Trial Progressing
• Intravitreal Diabetic Macular Edema (DME) Candidate KVD001 Phase 2 Trial Completion Expected H2 2019
• Oral Plasma Kallikrein Inhibitor Candidate KVD824 Dosing in First-in-Human Trial

KalVista Pharmaceuticals, Inc.(NASDAQ: KALV), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of small molecule protease inhibitors, today provided an operational update and released financial results for the fiscal third quarter ended January 31, 2019.

“We are pleased with the progress of the Phase 2 trial of KVD900 as we move through the regulatory and site set-up process,” said Andrew Crockett, Chief Executive Officer of KalVista. “KVD900 is our most advanced candidate for oral treatment of HAE and we continue to expect data late this year. Our latest oral plasma kallikrein inhibitor candidate, KVD824, has begun dosing in a first-in-human trial and we expect to provide an update on this around mid-year. In other ongoing clinical activity, enrollment is on track for our Phase 2 trial of KVD001, our intravitreal DME candidate.”

Third Quarter and Recent Business Highlights:

• Provided a clinical update on oral plasma kallikrein inhibitors currently in the clinic. KVD900 was advanced into a Phase 2 clinical trial as a potential oral on-demand therapy, which will investigate efficacy in at least 50 type 1 and type 2 HAE patients. The trial will be conducted at 10-15 sites in the UK, Germany and other European countries. This two-part study will evaluate the pharmacodynamic and pharmacokinetic properties of KVD900 as well as the efficacy of the drug versus placebo. KVD824 was named as the next oral plasma kallikrein inhibitor candidate and has commenced dosing in a first-in-human trial. The Company expects to give an update on KVD824 around mid-2019.
• Appointed Brian J. G. Pereira to Board of Directors. Brian is a veteran biopharmaceutical and healthcare leader with experience in financing and growing companies. He has been President and CEO of Visterra, Inc. since 2013 and previously served as President and CEO of AMAG Pharmaceuticals. Dr. Pereira’s experience in medical matters, clinical development and commercial infrastructure will be of great value to KalVista as we approach late stage development for our programs.
• Announced data from a poster presentation given at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting. The Company provided additional data from a Phase 1 single ascending dose study of KVD900, evaluating the efficacy and safety of tablet and capsule formulations of the drug in healthy adult males, with a food-effect crossover study. The data showed that a single 600 mg dose of KVD900 provided >90% inhibition of plasma kallikrein within 30 minutes of dosing and protected against high molecular weight kininogen cleavage for at least 10 hours. No significant food effect was observed on the pharmacodynamic profile of the 600 mg KVD900 tablet in fed and fasted states.

Upcoming Events:

• Presenting during a poster session at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, April 28 – May 2, 2019, in Vancouver, Canada:
  Presentation Date: Monday, April 29, 2019
  Presentation Time: 4.00pm-5.45pm EST
  Abstract Title: Novel oral plasma kallikrein (PKa) inhibitors KV998052 and KV998054 ameliorate VEGF-induced retinal thickening in a murine model of retina edema.
  Session: 289
  Session Title: Retinal Vascular Diseases II

Fiscal Third Quarter Financial Results:

• Revenue: Revenue was $3.9 million for the three months ended January 31, 2019, compared to $2.3 million for the same period in 2018. Revenue in the three months ended January 31, 2019 consisted of the recognition of a portion of the upfront payment from Merck related to the agreement signed in October 2017.
• R&D Expenses: Research and development expenses were $7.7 million for the three months ended January 31, 2019, compared to $4.5 million for the same period in 2018. The increase in R&D expense primarily reflects the ongoing clinical trials for KVD001 and KVD900 and preparation for KVD824 to enter the clinic.
• G&A Expenses: General and administrative expenses were $2.9 million for the three months ended January 31, 2019, compared to $2.1 million for the same period in 2018.
• Net Loss: Net loss was $4.0 million, or $(0.23) per basic and diluted share for the three months ended January 31, 2019, compared to a net loss of $5.2 million, or $(0.49) per basic and diluted share, for the same period in 2018.
• Cash: Cash, cash equivalents and investments were $111.1 million as of January 31, 2019.

https://www.biospace.com/article/kalvista-pharmaceuticals-reports-fiscal-third-quarter-results-march-14-2019/

Atossa up on expanded access for Endoxifen

Nano cap Atossa Genetics (NASDAQ:ATOS) is up 227% premarket on increased volume in response to the FDA’s sign-off on expanded access to Endoxifen for the post-mastectomy treatment of a single premenopausal estrogen receptor-positive (ER+) breast cancer patient.

The patient received a three-week course oral Endoxifen prior to her surgery.

According to the company, Endoxifen prevents the ER from functioning, adding that recent research suggests that it also destroys the receptor.

https://seekingalpha.com/news/3442771-atossa-227-percent-premarket-expanded-access-endoxifen