Kezar Life Sciences’ (NASDAQ:KZR) lock-up period is set to expire on Tuesday, December 18th. Kezar Life Sciences had issued 5,000,000 shares in its IPO on June 21st. The total size of the offering was $75,000,000 based on an initial share price of $15.00. Shares of the company owned by company insiders and major shareholders will be eligible for trade following the end of the lock-up period.
Monday, December 17, 2018
Novartis, Pfizer withdraw drug applications in Europe
- Pfizer and Novartis both withdrew drug applications earlier this month with the European Medicines Agency’s committee in charge of reviewing and recommending approval for therapies for human use, according to a Dec. 14 release from the regulatory agency.
- Novartis pulled back on canakinumab after the Committee for Medicinal Products for Human Use raised serious concerns in its review, including questions that the Swiss drugmaker conceded it could not address within the review’s timeframe. A company spokesperson told BioPharma Dive canakinumab is also being pulled from reviews in Switzerland, Australia and Canada.
- Pfizer withdrew Fyzoclad, a biosimilar of AbbVie’s Humira, from consideration for a limited label due to “a change in Pfizer’s strategy,” according to a company letter sent to the committee on Dec. 5. An application for the full label remains under review.
Novartis has encountered difficulty in getting canakinumab, the active ingredient in Ilaris, past regulators for broader indications. In October, U.S. regulators rejected the drug as a treatment for cardiovascular risk reduction. The pharma seems to have had no better luck in Europe.
Canakinumab got the FDA’s OK in 2009 and the European Commission’s approval in 2009 for certain rare auto-inflammatory disorders, but Novartis was eyeing a broader label for the monoclonal antibody, particularly one to help people who have already had a heart attack avoid major cardiovascular events, such as another heart attack or a stroke.
Novartis banked on a long-term cardiovascular study as its proof, which studied more than 10,000 participants after three years of treatment. Last year, the pharma rolled out the results, showing canakinumab beat placebo. Sell-side analysts dreamed it could turn canakinumab into a blockbuster.
That hasn’t panned out, however. Regulators raised concerns about the study and its outcomes, and the Swiss pharma could not address them in the approval timeframe.
The CHMP had “remaining concerns” when Novartis formally withdrew its application on Dec. 4., and called the data “not robust enough to clearly demonstrate” its efficacy in all patients who have had a heart attack. The committee’s provisional opinion at the time was the “modest” benefits did not outweigh increased risk of serious infections, according to a document from the regulator.
A Novartis spokesperson said canakinumab will continue to be studied in other disease areas.
Meanwhile, Pfizer’s reasons for withdrawing were much less clear, with its letter only stating a change in strategy. It did clarify it’s reasons were not about efficacy or safety of the Humira (adalimumab) biosimilar.
The committee said it was still evaluating initial documentation of the application when it was withdrawn.
The first copycats of the world’s top-selling drug hit the European market in October. Stronger patent protections in the U.S. have allowed AbbVie to line up settlements with multiple drugmakers for 2023 entry of copycats.
Pfizer became the seventh pharma to reach such a deal with AbbVie, which was announced a few days before the pharma withdrew the limited label application in Europe. The settlement allowed Pfizer to launch in Europe once it received a regulatory OK.
A Pfizer spokesperson said in an email to BioPharma Dive the full label application remains under review, and the company cannot comment further.
J&J CEO says he ‘unequivocally’ believes baby powder does not contain asbestos
Johnson & Johnson CEO Alex Gorsky said in an interview on CNBC’s “Mad Money” that, in response to a Reuters report from last week that the company knew for decades about asbestos in its talc-based baby powder, the company “unequivocally” believes that its talc-based baby powder does not contain asbestos. Gorsky added that many studies, some conducted by J&J, support the company’s claims. The CEO said that such studies were “independent” and involved nearly 100,000 patients, both men and women, for decades. Gorsky added that he remains “very confident” in the safety of J&J’s products.
https://thefly.com/landingPageNews.php?id=2838317
Path to vaccine or drug for late-onset Alzheimer’s
UT Southwestern researchers have succeeded in neutralizing what they believe is a primary factor in late-onset Alzheimer’s disease, opening the door to development of a drug that could be administered before age 40, and taken for life, to potentially prevent the disease in 50 to 80 percent of at-risk adults.
Apolipoprotein E (ApoE) is a protein that carries fatty substances called lipids and cholesterol around the brain and plays an important role in repair mechanisms. There are three major forms of ApoE (i.e., ApoE2, ApoE3, and ApoE4); individuals who carry ApoE4 are up to 10 times more likely to develop Alzheimer’s than those with ApoE2 and ApoE3 forms. ApoE4 promotes accumulation of the b-amyloid protein that causes the characteristic plaques seen in the brains of Alzheimer’s patients.
UT Southwestern molecular biologist and Alzheimer’s expert Dr. Joachim Herz, lead author of the study, which was published in the November issue of eLife said the goal of his team is to prevent the disease from ever manifesting. Late-onset Alzheimer’s generally is diagnosed about age 65 and is the most common cause of dementia in the elderly. “If we can negate the ApoE4 process early, we may be able to prevent late-onset Alzheimer’s altogether for many people so that they will never get sick,” Dr. Herz said.
ApoE4 has been shown to suppress and trap synaptic receptors within intracellular vesicles. However, how the ApoE4 gets trapped has remained a mystery until now. According to Dr. Herz, ApoE4 is the root cause of a “traffic jam” inside the cells that take up ApoE4 and this is associated with reduced recycling of intracellular endosomal transport vesicles. UTSW researchers found that lowering the pH of these endosomes, i.e., by making them more acidic, cleared the traffic jam: The scientists were able to completely reverse the ApoE4-induced recycling block in mice through pharmacological and genetic inhibition of the NHE6 protein, which acts to make the endosomal vesicles less acidic.
These findings suggest a novel potential therapeutic approach for the prevention of late-onset Alzheimer’s disease, Dr. Herz said. The vesicle traffic jam due to the selective loss of solubility of ApoE4 likely is the earliest mechanism at which the protein negatively affects nerve cells, Dr. Herz said.
Most Alzheimer’s research has focused on halting the formation of amyloid and tau protein aggregates once they exist in the brain and degeneration has already begun. “Our approach in this study was to stop the overall degeneration process earlier; that is, before the formation of these aggregates,” Dr. Herz said.
The next step is to develop tailor-made, small molecule inhibitors that can enter the brain efficiently and selectively block NHE6, he added.
“The beauty of NHE inhibitors is that these are small molecules that can be produced inexpensively and thus made widely available, in contrast to the more elaborate antibody-based therapies that are currently being evaluated in clinical trials. A simple pill could someday neutralize the risk of late-onset Alzheimer’s disease just as readily available statins are able to reduce the risk of cardiovascular disease,” Dr. Herz said.
Story Source:
Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.
Journal Reference:
- Xunde Xian, Theresa Pohlkamp, Murat S Durakoglugil, Connie H Wong, Jürgen K Beck, Courtney Lane-Donovan, Florian Plattner, Joachim Herz. Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer’s disease. eLife, 2018; 7 DOI: 10.7554/eLife.40048
CBD in marijuana may worsen glaucoma, raise eye pressure
One of the most commonly proposed uses of medical marijuana is to treat glaucoma.
But a study from researchers at Indiana University has found that a major chemical component in the substance appears to worsen the primary underpinning of the disease: a rise in pressure inside the eye.
The chemical that causes this rise in pressure is cannabidiol, or CBD, a non-psychoactive ingredient in cannabis that is increasingly marketed to consumers in products such as oil, gummies, creams and health food. It is also approved in many states as a treatment for conditions such as pediatric epilepsy.
The study was reported Dec. 14 in the journal Investigative Ophthalmology & Visual Science.
“This study raises important questions about the relationship between the primary ingredients in cannabis and their effect on the eye,” said Alex Straiker, an associate scientist in the IU Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences, who led the study. “It also suggests the need to understand more about the potential undesirable side effects of CBD, especially due to its use in children.”
The study, which was conducted in mice, specifically found that CBD caused an increase in pressure inside the eye of 18 percent for at least four hours after use.
Tetrahydrocannabinol, or THC, the primary psychoactive ingredient of marijuana, was found to effectively lower pressure in the eye, as has been previously reported. But the study found that the use of CBD in combination with THC blocked this effect.
Specifically, the study found that male mice experienced a drop in eye pressure of nearly 30 percent eight hours after exposure to THC alone. A lower pressure drop of 22 percent was also observed after four hours in male mice.
The effect was weaker in female mice. This group experienced a pressure drop of only 17 percent after four hours. No difference in eye pressure was measured after eight hours.
The results suggest that females may be less affected by THC, though it isn’t clear whether this extends to the substance’s psychoactive effects.
“This difference between males and females — and the fact that CBD seems to worsen eye pressure, the primary risk factor for glaucoma — are both important aspects of this study,” Straiker said. “It’s also notable that CBD appears to actively oppose the beneficial effects of THC.”
By comparing the effect of these substances on mice without specific neuroreceptors affected by THC and CBD, the IU researchers were also able to identify the two specific neuroreceptors — named CB1 and GPR18 — by which the first substance lowered pressure inside the eye.
“There were studies over 45 years ago that found evidence that THC lowers pressure inside the eye, but no one’s ever identified the specific neuroreceptors involved in the process until this study,” Straiker said. “These results could have important implications for future research on the use of cannabis as a therapy for intraocular pressure.”
Story Source:
Materials provided by Indiana University. Note: Content may be edited for style and length.
Journal Reference:
- Sally Miller, Laura Daily, Emma Leishman, Heather Bradshaw, Alex Straiker. Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Investigative Opthalmology & Visual Science, 2018; 59 (15): 5904 DOI: 10.1167/iovs.18-24838
HealthEquity upgraded to Overweight from Neutral at Cantor Fitzgerald
Cantor Fitzgerald analyst Steven Halper upgraded HealthEquity to Overweight with an $82 price target. The stock closed the trading day down 4%, or $2.46, to $59.63. Despite the recent pullback in the shares, HealthEquity’s fundamentals remain strong as the company continues to benefit from adoption of health savings accounts, Halper tells investors in a research note. The analyst believes the recent pullback in the stock is overdone and creates an attractive entry point.
FibroGen OKd in China for Treatment of Anemia in Chronic Kidney Disease
FibroGen, Inc. (FGEN) today announced that FibroGen (China) Medical Technology Development Co., Ltd. (FibroGen China) has received marketing authorization from the National Medical Products Administration (NMPA) for roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for the treatment of patients with anemia caused by chronic kidney disease (CKD) in patients who are dialysis-dependent (DD). The medicine can be prescribed to patients who use hemodialysis or peritoneal dialysis.
Anemia caused by CKD is associated with cardiovascular disease, hospitalization, cognitive impairment, and reduced quality of life, and has been shown consistently to increase the mortality risk in patients with CKD.1 Anemia becomes increasingly common among individuals with CKD as their disease progresses, affecting nearly all patients at the dialysis-eligible stage.1
Thomas B. Neff, Chief Executive Officer, FibroGen, said: “We believe roxadustat will make a significant difference for patients in China by addressing a substantial unmet medical need in the treatment of anemia associated with chronic kidney disease. This is an exciting milestone, as we are realizing our decade-long commitment to bringing innovative medicine to people in China. We look forward to bringing roxadustat to patients worldwide.”
Chris Chung, Managing Director, FibroGen China, said: “We are grateful to the patients and physicians in China who participated in our clinical studies. Almost ten years ago, FibroGen made the decision to develop roxadustat, a first-in-class investigational candidate, in China as a Domestic Class 1 Innovative Drug. It arose out of a commitment to give Chinese patients accelerated access to critically needed innovative medicines.”
Roxadustat (China Approved Drug Name: 罗沙司他; Chinese brand name: 爱瑞卓®) is the first approved oral HIF-PHI medicine. This approval is supported by an open-label, active-control 26-week Phase 3 trial in DD-CKD patients with anemia who were previously treated with various forms of locally manufactured injectable recombinant erythropoietin products. In the trial, these DD-CKD patients were then randomized to receive either roxadustat or ESPO® (利血宝®) brand epoetin alfa, manufactured and marketed by Kyowa Hakko Kirin.
FibroGen China has also completed a roxadustat China Phase 3 placebo-controlled trial in non-dialysis-dependent (NDD) CKD patients. The addition of NDD patients to the label is expected once regulatory inspections of the clinical trial sites by the NMPA are completed.
Anemia commonly develops in association with CKD. Based on a large-scale cross-sectional survey performed between September 2009 and September 2010 and published in the Lancet, there are an estimated 120 million CKD patients in China, including estimated 0.5 million patients on dialysis who may be suffering from anemia, a number that is increasing significantly.2,3
AstraZeneca and FibroGen China are collaborating on the development and commercialization of roxadustat in China. FibroGen China, based in Beijing, is a subsidiary of FibroGen, Inc. that sponsored the development and registration of roxadustat as a Domestic Class 1 Innovative Drug. FibroGen China conducted the China Phase 3 clinical trials and submitted the New Drug Application for registration of roxadustat to the Chinese regulatory authorities. Following this approval, AstraZeneca will manage commercialization activities in China, and FibroGen China will manage commercial manufacturing and medical affairs as well as continued clinical development and regulatory affairs. AstraZeneca and FibroGen expect to launch roxadustat in China in the second half of 2019.
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