Zynerba extends rally as FDA explores cannabis derived product regulation

The FDA will hold a public hearing on potential regulatory pathways for cannabis products on May 31

Zynerba (ZYNE) is on the rise for a second straight session on Wednesday after the Food and Drug Administration issued a statement yesterday on new steps to advance the agency’s continued evaluation of potential regulatory pathways for cannabis-containing and cannabis-derived products. Commenting on the FDA news, Ladenburg analyst Michael Higgins said he believes the agency will be taking further steps in 2019 to remove any non-prescription products being sold that include tetrahydrocannabinol and cannabidiol, which he views as favoring the market adoption of Zynerba’s Zygel.

POTENTIAL REGULATORY PATHWAYS: The FDA issued a statement yesterday from outgoing Commissioner Scott Gottlieb on new steps to advance the agency’s continued evaluation of potential regulatory pathways for cannabis-containing and cannabis-derived products, in which he stated in part: “In recent years, we’ve seen a growing interest in the development of therapies and other FDA-regulated consumer products derived from cannabis and its components, including cannabidiol, or CBD…We also recognize that stakeholders are looking to the FDA for clarity on how our authorities apply to such products, what pathways are available to market such products lawfully under these authorities, and how the FDA is carrying out its responsibility to protect public health and safety with respect to such products.” The FDA is announcing a number of new steps and actions to advance its consideration of a framework for the lawful marketing of appropriate cannabis and cannabis-derived products under its existing authorities, Gottlieb said. These new steps include: A public hearing on May 31, as well as a broader opportunity for written public comment, for stakeholders to share their experiences and challenges with these products, including information and views related to product safety; The formation of a high-level internal agency working group to explore potential pathways for dietary supplements and/or conventional foods containing CBD to be lawfully marketed; including a consideration of what statutory or regulatory changes might be needed and what the impact of such marketing would be on the public health; Updates to its webpage with answers to frequently asked questions on this topic to help members of the public understand how the FDA’s requirements apply to these products; and the issuance of multiple warning letters to companies marketing CBD products with “egregious and unfounded claims that are aimed at vulnerable populations.”

ANALYST SEES NEWS FAVORING ZYNERBA: In a research note to investors yesterday, Ladenburg’s Higgins said he believes the FDA will be taking further steps in 2019 to remove any non-prescription products being sold that include THC and CBD, while allowing the production and marketing of hemp as it follows the Agriculture Improvement Act of 2018. He sees the removal of current CBD-containing foods, lotions, snacks, oils and other embodiments containing CBD favoring the market adoption of Zynerba’s Zygel. The analyst noted that he has “long expected” the availability of over the counter CBD products during Zygel’s marketing – assuming positive pivotal data in Fragile X patients in the second half of 2019 and approval in the second half of 2020 – but the stance of the agency suggests less availability of CBD-containing products for consumers to choose from. Further, Higgins believes FDA’s publication reflects the agency’s “loss of patience” with these products as the number of and marketing of these products have become “more ubiquitous and aggressive.” Additionally, the analyst thinks the agency may provide and/or reinforce its position against the allowance of marijuana-based products as food or dietary products in its May 31 hearing. He reiterated a Buy rating and $26 price target on Zynerba shares.

OTHERS TO WATCH: Other publicly traded companies in the cannabis space include Aphria (APHA), Aurora Cannabis (ACB), CV Sciences (CVSI), CannTrust Holdings (CNTTF), Canopy Growth (CGC), Cronos Group (CRON), General Cannabis (CANN), India Globalization Capital (IGC), MediPharm Labs (MLCPF) and Tilray (TLRY).

https://thefly.com/permalinks/entry.php/id2888175/ZYNE;APHA;ACB;CVSI;CNTTF;CGC;CRON;CANN;IGC;MLCPF;TLRY-Zynerba-extends-rally-as-FDA-explores-cannabis-derived-product-regulation

Piper says Kura’s potential patient population for tipifarnib keeps growing

After Kura Oncology presented additional data on tipifarnib, a farnesyltransferase inhibitor/HRAS inhibitor that downregulates expression of CXCL12, Piper Jaffray analyst Tyler Van Buren said the number of potential indications for the drug “continues to multiply” as initial clinical data suggest diffuse large B-cell lymphoma and cutaneous T-cell lymphoma patients could benefit from treatment in addition to the already identified cancer indications. The “broad mechanism of tipifarnib is becoming clear” and the potential patient population keeps growing, “well beyond what investors are currently appreciating,” according to Van Buren. He keeps an Overweight rating on Kura shares.

https://thefly.com/landingPageNews.php?id=2888185

Catalyst Initiates Phase 2b Trial for Treatment of Hemophilia B

Catalyst Biosciences, Inc. (Nasdaq:CBIO), today announced the initiation of enrollment in a Phase 2b study of dalcinonacog alfa (DalcA), a next-generation subcutaneously (SQ) administered Factor IX (FIX) therapy being developed for the treatment of hemophilia B.

The data from our Phase 1/2 clinical study demonstrated that DalcA is highly efficacious for the treatment of hemophilia B and can achieve Factor IX activity levels well above the 12% expected to prevent spontaneous bleeding, said Nassim Usman, Ph.D., president and chief executive officer of Catalyst. We anticipate that this Phase 2b study will further demonstrate DalcAs safety and efficacy as a subcutaneous prophylactic treatment option. Individuals with severe hemophilia B face a lifetime of complicated intravenous treatment regimens. We believe that DalcA may offer a conveniently-dosed subcutaneous prophylactic treatment option that could significantly improve the quality of life for those suffering from severe hemophilia B.

The open-label Phase 2b study will evaluate the ability of DalcA to maintain steady state FIX levels above 12% in individuals with severe hemophilia B. The trial will enroll up to six subjects who will receive a single intravenous dose, followed by daily subcutaneous (SQ) doses of DalcA for 28 days. Pharmacokinetics, pharmacodynamics, safety and tolerability of daily SQ dosing and anti-drug antibody formation will also be monitored. The trial is expected to be completed in the second half of 2019.

https://www.marketscreener.com/CATALYST-BIOSCIENCES-INC-34019199/news/Catalyst-Biosciences-Initiates-a-Phase-2b-Trial-of-Dalcinonacog-Alfa-for-the-Treatment-of-Hemophil-28343720/

Glaxo, ViiV: Juluca maintains HIV viral suppression at 148 weeks

ViiV Healthcare today presented three year results from the SWORD 1 & 2 studies, demonstrating that 84% (432/513) of participants who switched from their current three- or four-drug antiretroviral regimen to a 2-drug regimen of dolutegravir (ViiV Healthcare) and rilpivirine (Janssen Sciences Ireland UC, part of the Janssen Pharmaceutical Companies of Johnson & Johnson) maintained viral suppression (viral load ≤50 copies/mL).¹ These results were presented at the 25th Annual Conference of the British HIV Association (BHIVA) taking place from 2-5 April in Bournemouth, UK.

https://www.marketscreener.com/GLAXOSMITHKLINE-9590199/news/GlaxoSmithKline-ViiV-Healthcare-announces-Juluca-dolutegravir-rilpivirine-maintains-HIV-viral-su-28343950/

Novartis’s Alcon spinoff ousts Baer from Swiss benchmark SMI

Novartis’s spinoff of its eyecare division Alcon, set for Tuesday April 9, marks the largest Swiss stock deal in a decade and forces a reshuffle of the benchmark Swiss Market Index (SMI) as private bank Julius Baer gets booted out.

Novartis has estimated Alcon’s value at around 25 billion Swiss francs (19.06 billion pounds), while some analysts predict an initial market capitalisation of 21 billion francs ($21 billion) to 23 billion, implying shares worth from 43 to 47 francs.

By contrast Baer’s value has tumbled by a third in a year to 9.3 billion francs. It will instead be included in the SMIM index, replacing Aryzta, SIX Swiss Exchange said after Tuesday’s market close.

Dominated by Nestle, Novartis and Roche, the SMI is Switzerland’s most important index. Membership is based on market capitalisation, adjusted for the free float of readily tradable shares in its constituents.

Alcon is being spun off in a one-for-five share deal announced by Novartis last June as it focuses on new drugs rather than the surgical devices and contact lenses Alcon makes.

Joining the SMI may boost demand from funds focusing on the top Swiss companies. Yet Alcon’s inclusion means healthcare and medical technology will weigh even more heavily on the SMI.

Novartis’s weighting had been capped 18 percent, but with Alcon the two will account for up to 21.5 percent of the SMI, Zuercher Kantonalbank analysts estimated on Wednesday.

Novartis’s biggest owners – BlackRock, the Sandoz family, Capital Research Global Investors and Vanguard Group – will have similar holdings in Alcon, between 2.5 percent and 4.5 percent.

“We anticipate incremental buying of Alcon shares by some funds seeking to build a full-size position, offset by others not wanting to own a non-pharma eyecare company,” Jefferies analyst Peter Welford said.

Novartis bought Alcon’s eye surgery and contact lens portfolio in stages through 2010 for $52 billion from Nestle, only to see it lose ground to competitors as sales and profitability slipped.

In surgical equipment, Alcon competes against Johnson & Johnson, Germany’s Zeiss and Bausch in a $9 billion per year market. Rivals in vision care, worth $14 billion annually, include J&J, Cooper and Bausch.

In 2016, a new Alcon head, Mike Ball from Hospira, redoubled research and marketing spending to resurrect revenue, before Novartis chief Vas Narasimhan decided to shed the division.

The last comparable-sized Swiss listing was in 2010, when oil driller Transocean floated on the same day its Deepwater Horizon rig exploded in the Gulf of Mexico.

https://www.marketscreener.com/ARYZTA-3994384/news/Novartis-s-Alcon-spinoff-ousts-Baer-from-Swiss-benchmark-SMI-28344089/

Achillion reaches threshold enrollment in Phase 2 trials for C3 glomerulopathy

Achillion achieved threshold enrollment in the Phase 2 trials of ACH-4471 for patients with C3 glomerulopathy or C3G, a devastating disease affecting the kidney for which there is no approved therapy. ACH-4471 will be evaluated in the six-month trial with 11 patients and the 12-month open-label trial with 12 patients. The company expects to present data from these two Phase 2 trials, along with real-world C3G data, to the FDA in Q4. The objective of the six and 12-month proof-of-concept trials is to evaluate the safety and efficacy of ACH-4471 in patients diagnosed with C3G. The measures being evaluated include changes in clinical manifestations of C3G including proteinuria and estimated glomerular filtration rate at the end of the treatment period and changes in kidney biopsy from baseline.

https://thefly.com/landingPageNews.php?id=2887810

AFM Cases in Kids: A Mystery That Needs Solving

More research is needed into acute flaccid myelitis (AFM), the polio-like condition in children caused by unknown illnesses, although non-polio enteroviruses remain among the chief suspects, researchers at the National Institute of Allergy and Infectious Diseases (NIAID) argued.

While there have been temporal associations with epidemics of AFM and the non-polio enterovirus, enterovirus (EV)-D68, there has still been no definitive cause found for these spikes in AFM cases, reported David Morens, MD, and Anthony Fauci, MD, both of NIAID in Bethesda, Maryland, and colleagues, writing in mBio, an open-access journal of the American Society for Microbiology.

AFM made national news in 2018, with a total of 228 confirmed cases in 41 U.S. states, and four confirmed cases in 2019. The spike in reported cases in 2018 was so dramatic that in October, the CDC announced they would start tracking AFM cases.

Acute flaccid myelitis was characterized by Morens and colleagues as a “newly coined term” for a subset of cases of the “long-recognized syndrome of acute flaccid paralysis … in which cord myelitis is documented.” It was described as a “seemingly novel condition” in 2010, with the first large outbreak reported in 2014.

Researchers also discussed the epidemiology of non-polio enteroviruses (NPEVs), which are more commonly transmitted by the respiratory route, and can cause a wide variety of “disease syndromes,” such as respiratory infections, conjunctivitis, myositis, and occasionally, sporadic AFM. They noted that the first non-polio enterovirus was isolated from a child with AFM.

Then they cited the strange seasonal pattern of AFM and non-polio enterovirus, enterovirus (EV)-D68, where “AFM epidemics in the United States have recurred in 2-year cycles of increasing magnitude, usually during seasonal EV-D68 circulation.” Indeed, just as AFM cases spiked in 2018, the CDC recently reported a large spike in cases of EV-D68-associated respiratory illness (from two cases in 2017 to 358 cases in 2018).

However, EV-D68 is not the smoking gun for all AFM cases. In October, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, said in a press briefing that in some AFM cases, researchers found enterovirus, but in some cases, they found rhinovirus.

Still, Morens and colleagues offered up some hypotheses for the association between AFM and EV-D68, characterizing the link between the two as “circumstantial, but nonetheless strong.”

“A precipitating EV-D68 infection, often with low-level viral replication, may well have run its course by the time of onset and diagnosis of AFM, several days to a week or more later,” they wrote. “Early transient viremia during the respiratory prodrome might also have resolved by the time of AFM onset.”

The authors then cited several sobering “plot twists” — namely that AFM was associated with both EV-D68 and enterovirus A71, “a well-known cause of both hand-foot-and-mouth disease and AFM that has been problematic in other regions of the world, but historically less so in the United States.”

“Could we be entering some kind of new epidemic era, in which fundamental but unappreciated determinants of enterovirus evolution and spread are changing?” Morens and colleagues said, adding that another explanation could be that epidemic AFM may result from “rapid viral evolution via mutation and recombination that leads to increased viral pathogenicity.”

Clinically, researchers noted that AFM is difficult to treat, with therapies such as “intravenous immunoglobulin, glucocorticoids, plasma exchange, and antiviral drugs such as pleconaril” being largely unsuccessful. There is mounting evidence, they said, for early intensive physical therapy, similar to that for polio.

Future directions for research include non-polio enterovirus specific diagnostics and virus-specific serologic tests to support epidemiologic studies, as well as experimental animal models, which could identify gene markers and potentially drug therapies.

“Until such time as the causes of the AFM epidemic are better understood, development of preventive vaccines will remain challenging,” Morens and colleagues concluded.

Fauci is the director of NIAID.

Morens and co-authors disclosed no relevant relationships with industry.

• Primary Source

  mBio

  Source Reference: Morens DM, et al “Acute flaccid myelitis: Something old and something new” mBio 2019; DOI: 10.1128/MBio.00521-19.

https://www.medpagetoday.com/infectiousdisease/generalinfectiousdisease/78980