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.
Wednesday, April 3, 2019
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.
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.
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.
Boots warns of possible store closures
The US owner of pharmacy chain Boots has warned of possible store closures in the UK as it tries to cut costs.
Walgreens Boots Alliance said it would take “decisive steps” to reduce costs as part of a company-wide “significant restructuring”.
The move comes after the chain said it had suffered its “most difficult quarter” since the firm’s formation with UK like-for-like sales down 2.3%.
The chain has 2,500 stores across the UK, employing around 60,000 staff.
Chief executive Stefano Pessina said market challenges had “accelerated” in the three months to the end of February, but that it had failed to respond rapidly enough “resulting in a disappointing quarter”.
“We are going to be more aggressive in our response to these rapidly shifting trends,” he added.
Actions announced include “optimising its store footprint” and increasing its planned annual cost savings from $1bn to $1.5bn.
The cost cuts follows Boots’ announcement in February that 350 jobs were at risk in its Nottingham head office amid plans to reduce costs by 20%.
Overall earnings for the firm’s second quarter were down 14.3% compared to the same period last year. The company said it was now expecting profit to be flat for the full year, down from its earlier guidance of 7% to 12% growth.
Tuesday, April 2, 2019
Does improved safety boost Allergan’s case for wet AMD challenge to Lucentis?
Allergan has chalked up some flattering safety data for abicipar as it refines the eye drug’s manufacturing processes in preparation of an impending BLA filing. But whether or how much that matters is still up for debate.
In an open-label, single-arm study, investigators reported that the incidence of intraocular inflammation was 8.9% — lower than the rate observed in prior Phase III studies, which hovered around 15%. The MAPLE trial recruited 123 age-related neovascular macular degeneration (or wet AMD) patients and administered the injection five times over 28 weeks.
“The results of this open-label study enabled us to assess improvements to the manufacturing process for abicipar. The safety profile demonstrated in MAPLE gives us confidence to proceed and scale up manufacturing,” said David Nicholson, chief research and development officer. “We plan to submit the abicipar BLA and continue to pursue manufacturing process improvements as we develop larger scale studies in additional disease states, such as diabetic macular edema.”
Any little improvement could be crucial as Allergan and its allies at Molecular Partners go up against the entrenched market leaders, Regeneron’s Eylea and Novartis’ Lucentis, both approved for multiple indications other than wet AMD, which is far less common but much more severe than dry AMD. And the two giants are each advancing follow-on efforts of their own.
Any little improvement could be crucial as Allergan and its allies at Molecular Partners go up against the entrenched market leaders, Regeneron’s Eylea and Novartis’ Lucentis, both approved for multiple indications other than wet AMD, which is far less common but much more severe than dry AMD. And the two giants are each advancing follow-on efforts of their own.
The new inflammation rates, though, might still do little to change investors’ skeptical views on the commercial prospect, said Umer Raffat of Evercore ISI.
Raffat notes that severe inflammation registered at 1.6% in the MAPLE trial, compared to 3.2% to 3.7% observed in previous Phase III studies.
AGN feels strongly that it’s really just the severe inflammation that matters … and that it’s now at a well controlled rate (<2%) … and that mild inflammation is asymptomatic.
If we agree with AGN’s logic, there is an impt piece of data that hasn’t been disclosed about MAPLE: the rate of moderate inflammation. (we know mild+mod+severe = 8.9% … and severe is 1.6% … but what is moderate? if we go by Ph 3 results, moderate could be half of this 8.9% … but unclear if that actually happened in MAPLE also).
To put it bluntly: “It will be a ‘show-me’ story at launch.”
Analysts for SVB Leerink was even more doubtful, noting:
Reported incidence of intraocular inflammation (IOI) was 8.9% in the MAPLE study, which was lower than prior Phase 3 studies (>15% after 1 year of treatment), but still significantly higher than the rate observed in Novartis’ (NVS, NR) Lucentis and Regeneron’s (REGN, OP) Eylea, which we think would limit its success to be a real player in the space.
Investors seem to be sitting this one out for now. Allergan $AGN shares are slightly in the red this morning, dipping 0.33%, or $0.5, pre-market.
The duo has previously touted Phase III data suggesting abicipar is non-inferior to Lucentis on both tested schedules, though the incidence of intraocular inflammation remained a sore point given that less than 1% of the patients on the rival drug experienced it.
Where Allergan is hoping to stand out is the dosing regimen, a fixed 12-week regimen that could “greatly reduce the treatment burden” according to Cleveland Clinic Cole Eye Institute’s Peter Kaiser. That’s thanks to Molecular Partners’ DARPin technology, which it says has higher stability and potency than monoclonal antibodies.
A BLA is still slated for the next two months, Allergan and Molecular Partners say, as previously reported.
Doctors Curing Over 70 Different Diseases With Treatment From the 1950s
Bone marrow transplants are both incredibly risky as well as expensive procedures. Nonetheless, they are still effective and have been used by doctors since the 1950s, with many successful procedures completed over the years.
However, because of their inherent risk, bone marrow transplantation is typically only ever used as a last resort after every other possible treatment has been tried and failed.
The Treatment and How It Works
Bone marrow itself is the spongy tissue that lies at the center of bones and it contains special stem cells that are responsible for producing millions of blood cells every day. In order to do a bone marrow transplant, the patient’s current bone marrow needs to be destroyed in order to pave the way for the donor cells. This is accomplished through intensive chemotherapy or radiotherapy that wipes out the bone marrow while also suppressing the patient’s immune system so that it doesn’t attack the new bone marrow after transplantation.
A donor is also required for a bone marrow transplantation. Some patients may be able to use their own bone marrow by saving some in advance, but more often than not, they need to have a donor give their bone marrow stem cells to them. The donor doesn’t have to be related to the patient, but this is pretty common.
Once the patient’s bone marrow has been completely removed and their immune system has been suppressed, the actual transplantation can begin.
The actual transplantation itself is a pretty simple, and painless, process. The bone marrow stem cells are infused into the patient through their central line, through which they eventually find their way into the patient’s bones, where they begin creating new blood cells.
There are a number of potential side effects and complications that can arise from the bone marrow transplantation process, which makes it inherently risky. These can include anemia, fluid overload, respiratory disease, graft-versus-host disease, organ damage, and a myriad of different infections.
Despite the potential dangers and uncertainty involved with bone marrow transplantation, many patients find that is their only hope to live a healthier life and opt to try it.
What Bone Marrow Transplantation Can Cure
The number of different diseases that a bone marrow transplant is capable of treating is staggering. More than 70 diseases have been successfully treated by bone marrow transplantation so far. This includes Hodgkin’s lymphoma, severe aplastic anemia, sickle cell disease, testicular cancer, severe combined immunodeficiency, acute myeloid leukemia, and many more. People who suffer from any of these debilitating diseases could potentially find relief through a bone marrow transplant.
Along with treating a myriad of diseases, bone marrow transplants are also done for those who have had their bone marrow destroyed by intensive cancer treatments. Knowing that a patient can receive a bone marrow transplantation allows doctors the ability to give them higher doses of chemotherapy or radiation to treat their cancer, giving the patient a better outcome overall. This means bone marrow transplants indirectly aid with curing cancer as well.
The Future of Bone Marrow Transplants
While we already know that bone marrow transplants are capable of treating or helping with the treatment of, over 70 different diseases, researchers are always looking into other illnesses that it could be used as a treatment for.
Most recently, bone marrow transplantation has been used to treat human immunodeficiency virus (HIV) successfully twice now. In both of these cases, the patients were undergoing bone marrow transplantation for something completely unrelated to their HIV but then discovered that it ended up curing them of HIV as well.
While this is promising news for the future of HIV treatments, the researchers who studied one of the patients are leery of calling it a cure just yet and a lot more research needs to be done before it becomes a viable treatment for those suffering from HIV. But if future studies show that it does, in fact, cure HIV, then it could offer the millions of people infected with HIV a way to finally be cured of this crippling virus.
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