Shingrix and Trelegy shield Glaxo from Advair fallout

GlaxoSmithKline is expecting flat earnings this year, having earlier forecast a decline, as rising sales of new drugs have helped offset the impact of generics on its Advair blockbuster in the US.

The star of the show in the third quarter was shingles vaccine Shingrix, sales of which rose by 87% to reach £535 million, well ahead of analyst expectations, on the back of strong uptake in the US, Canada and Germany.

New respiratory drugs Nucala (mepolizumab) for severe asthma and Advair follow-up Trelegy (fluticasone furoate, umeclidinium, and vilanterol) made a solid supporting cast in the three-month period. Nucala rose 40% to £203 million, while Trelegy for chronic obstructive pulmonary disease (COPD) more than doubled to £139 million.

The growth products helped GSK to a 16% increase in turnover to £9.39 billion, despite Advair continuing its steady decline with a fall of a third to £418 million, with a two-thirds decline in the US market.

The turnover increase was improved by the consolidation of Pfizer’s consumer health business into a new joint venture, but even without that boost was still up 11%.

GSK chief executive Emma Walmsley has said since taking the helm that GSK needs its new products to fire on all cylinders while it revamps a new product portfolio that has been viewed as a lacklustre, and the first objective seems to be on track, with the company raising its earnings guidance for the year from a loss to flat.

On the second, Walmsley said GSK is gearing up for three new filings in oncology before the end of the year.

The includes BCMA-targeting antibody-drug conjugate belantamab mafodotin for fourth-line multiple myeloma treatment, as well as recently-acquired PARP inhibitor Zejula (niraparib) as a first-line maintenance therapy for ovarian cancer and PD-1 inhibitor dostarlimab in second-line endometrial cancer.

Trelegy has also been filed for approval in asthma, and Nucala picked up its first approval – in Europe – in a new self-administered formulation that should help cement its position as the lead biologic for severe asthma in the market, said Walmsley.

It wasn’t all positive news, however. GSK’s HIV franchise – sold via its ViiV joint venture – has been among its best performers for some time, but overall revenues for the business were flat in the third quarter due to increased competition, mainly from arch-rival Gilead Sciences.

GSK has been pushing its two-drug combinations for HIV such as Juluca (dolutegravir/rilpivirine) and new launch Dovato (dolutegravir/lamivudine), but chief financial officer Iain Mackay said the company “has anticipated it will take several quarters for them to become a significant contributor to growth”.

Together the two new drugs made £119 million in the third quarter, which GSK said offset declines in three-drug combination Triumeq (abacavir/dolutegravir/lamivudine), which has been hit by competition, notably from Gilead’s fast-growing Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide).

There was also the usual update on R&D casualties, which this time included  RIP1k inhibitor GSK3145095 for pancreatic cancer, and PI3Kd inhibitor GSK2292767 for respiratory diseases.

Shingrix and Trelegy shield GSK from Advair fallout

Astellas cuts $795m deal with Pandion for type 1 diabetes drugs

Astellas Pharma is boosting its early-stage pipeline with a $45 million upfront deal to license bispecific antibodies from US biotech Pandion Therapeutics with potential in the treatment of type 1 diabetes.

The exclusive deal, which includes another $750 million in potential milestone payments, will allow the Japanese pharma group to tap into Pandion’s R&D programme for type 1 diabetes and other autoimmune diseases affecting the pancreas.

Pandion focuses on developing proteins, antibodies and bispecifics that activate immune pathways that suppress uncontrolled immune responses, which it combines with tissue-selective ‘tethers’ to focus their effects on target organs.

It has been working on type 1 diabetes since December 2018, when it received funding to launch a programme in this area from DRF T1D Fund, a venture philanthropy fund exclusively devoted to finding and funding type 1 diabetes therapies.

Under the terms of the deal, Pandion will come up with multiple bispecific drug candidates designed to tackle the autoimmune reaction to insulin-producing pancreatic cells that leads to type 1 diabetes, with Astellas taking over their development from the preclinical stage onwards.

Type 1 diabetes is treated using insulin replacement therapy, but so far no treatment has been identified that can tackle the autoimmune mechanism that underpins the disease.

The hope is that one day immunotherapies could preserve the beta cells in the pancreas that produce insulin, and free patients from insulin injections or pumps which still leave patients vulnerable to complications affecting the eyes, kidneys, heart and nerves.

Other companies like Novo Nordisk and Sanofi are working on transforming stem cells into beta cells that could restore insulin production by the body, using vaccines to reduce the expression of cytokines linked to the autoimmune process, or developing drugs that can stimulate immune cells that suppress it.

“Our tissue targeted immune effectors are designed to directly address this aberrant immune response and modify the disease at the site of immune attack,” said Pandion’s chief executive Rahul Kakkar.

Astellas’ involvement “will greatly accelerate our R&D efforts and build upon our existing collaboration with the JDRF T1D Fund,” he added.

The Japanese company is already a player in diabetes with products like SGLT2 inhibitor Suglat (ipragliflozin), which was approved for type 2 in 2014 and as an add-on to insulin in type 1 diabetes last year.

Astellas cuts $795m deal with Pandion for type 1 diabetes drugs

Eloxx Pharma up 19% on positive ELX-02 data

Thinly traded micro cap Eloxx Pharmaceuticals (ELOX +19.2%) is up on almost 50% higher volume, albeit on turnover of only 127K shares, in reaction positive Phase 1 results for cystic fibrosis candidate ELX-02. The data were presented at the North American Cystic Fibrosis Foundation Conference in Nashville, TN.

ELX-02 showed favorable pharmacokinetic activity, high bioavailability and an acceptable safety profile dosed subcutaneously twice weekly.

Phase 2 studies are underway assessing a daily 50 mg/mL dose.

ELX-02 is a eukaryotic ribosomal selective glycoside, a molecule that modulates the ribosome, a part of the cell that plays a major role in protein production. It is designed to increase the read-through activity in patients with nonsense mutations, enabling the production of enough full-length protein to restore biochemical activity. CF is caused by the absence of or dysfunction in a protein called CFTR resulting from mutations in the gene that encodes the protein.

Management will host a conference call on Tuesday, November 5, to discuss the data.

https://seekingalpha.com/news/3512594-eloxx-pharma-19-percent-positive-elxminus-02-data

How measles infections can wipe away immunity to other diseases

Measles wipes out some of the immunity to other diseases that children acquire through vaccinations and infections, leaving them more vulnerable to illness for months and even years afterward, two new studies published Thursday report.

The findings help explain why countries that start to vaccinate children against measles see pediatric death rates drop substantially, beyond just the decrease that would be expected with the prevention of measles deaths.

The first paper, published in Science, showed that children infected with measles lost between 11% and 73% of their antibodies after infection. The authors, from Harvard University, noted the children studied had been healthy and well-nourished before contracting measles, and the impact on malnourished children in parts of the developing world is likely greater still.

Peoples’ immune systems are like blackboards onto which immunological experiences — the antibodies they developed after contracting the flu or getting vaccinated against chickenpox and polio — are written. Measles infection erases big sections of the text, an effect sometimes called immune amnesia.

“The immune system forgot what it once knew,” said Stephen Elledge, senior author of the Science paper and a professor of genetics at Harvard Medical School.

The second paper, from researchers in Europe, was simultaneously published in the journal Science Immunology.

The damage isn’t to the immune system itself — it is still capable of producing antibodies to protect against threats it encounters after measles infection. But children who have had measles will lose some of the protection they had developed from any previous immunizations and infections.

Dr. Michael Mina, first author of the Harvard paper, said the phenomenon bears some similarities to the one that takes place after HIV infection. HIV also infects immune system cells.

“If you took the first 10 years of somebody having HIV and you squished that into a few weeks, that’s the kind of memory damage and immune damage you get from measles,” Mina, an assistant professor of epidemiology at Harvard’s T.H. Chan School of Public Health, told STAT.

“You have this really rapid [antibody] decline with measles, and then a slow increase,” he said. “Whereas with HIV you have essentially a slow decrease but you never return back to baseline without therapy.”

Paradoxically, measles infections generate a very strong immune response against measles in the future, one that in the vast majority of cases protects for a lifetime.

For years there have been questions about why measles vaccinations decreased childhood deaths overall, with some people arguing that the vaccine might actually be boosting existing immunity to other pathogens, even though it is designed to protect only against measles.

But there was skepticism about that explanation. And research done in animals showed the measles virus infects immune cells, killing some.

Mina thought the explanation needed to be turned on its head. It wasn’t that the vaccine was boosting overall immunity — it was preventing an infection that damaged the work the immune system had done to date.

“To me it seemed like a fairly obvious question to ask: Maybe it’s actually erasing immune memory?” he said.

In 2015 he and some colleagues published a paper in Science suggesting the effect is lasting. While the immune system’s functional ability bounces back pretty quickly after measles infection, it can take several years to re-establish the antibodies the infection wiped away.

The 2015 study was based on epidemiological data. In the new paper, Mina, Elledge, and colleagues used a tool Elledge’s lab developed — called VirScan — which actually detects thousands of types of antibodies and their targets.

Using the tool, they were able to show and quantify the damage measles infection inflicted, using blood samples from Dutch children from a religious community that did not vaccinate its children. Researchers in the Netherlands drew blood samples from the children during a 2013 measles outbreak, creating a valuable bank of before and after samples used by both groups that published Thursday.

The European work, led by Velislava Petrova of the Wellcome Sanger Institute at Cambridge University, looked at the effect of the measles on B cells, which generate antibodies. Stores of the cells, created in the bone marrow, were depleted by the virus — an effect, they said, that provides a biological explanation for why child deaths not related to the measles increase for several years after a measles outbreak.

Mina and Elledge both suggested doctors may want to consider re-vaccinating children and perhaps even adults who have been infected with measles. And the papers argue that this is further proof of the importance of broad use of measles vaccine.

Dr. Saad Omer, director of Yale University’s Institute for Global Health, said while the work is important, he is not certain it will sway people who object to vaccination. The measles vaccine is a particular target of the anti-vax movement.

“It may impact a few fence sitters, along with other messages,” said Omer. “But on its own I don’t think it would lead to a substantial change in perception.”

Omer said there is already a wealth of good science supporting the importance of measles vaccines and yet a small but vocal proportion of the population does not find it persuasive.

How measles infections can wipe away immunity to other diseases

CHS stock plunges after announcing debt swap plan

Shares of Franklin, Tenn.-based Community Health Systems closed Oct. 30 at $3.82, down 16.6 percent from the day prior.

The decline came the day after the 102-hospital chain released its third-quarter earnings results and plans for a debt swap.

CHS revenues declined 5.9 percent in the third quarter of 2019. The company’s third-quarter loss totaled $17 million, which was a significant improvement from the $325 million loss it reported in the third quarter of 2018.

Though the company’s loss narrowed in the most recent quarter, CHS is still carrying a long-term debt load of nearly $3.3 billion.

On Oct. 29, CHS announced plans to offer $700 million in new senior secured notes due in 2027 and up to $1.9 billion in senior unsecured notes due in 2028 in exchange for its $2.6 billion worth of outstanding senior unsecured notes due in 2022.

Investors are likely concerned about the proposed debt swap plan because it would increase how much CHS pays in interest, according to The Motley Fool. Eight percent of CHS’ revenue currently goes toward interest expense, according to the report.

https://www.beckershospitalreview.com/finance/chs-stock-plunges-after-announcing-debt-swap-plan.html

Apple reports modest revenue growth, led by 54% surge in wearables

Apple reported total revenues of $64 billion for the fiscal fourth quarter ended Sept. 28, a year-over-year increase of 2 percent, in an earnings report released Oct. 30.

The modest increase was led by sizable growth in the company’s services, wearables and iPad sectors. Revenues in the services segment increased 17 percent year-over-year to reach an all-time high of $12.5 billion, while wearables experienced more than 50 percent annual growth to reach revenues of $6.5 billion.

Following the release of the report, Apple CEO Tim Cook spoke in an earnings call about how a significant portion of the wearables division’s success is due to the Apple Watch’s health and fitness tracking features being an “illustration of Apple’s commitment to your health,” according to iMore’s transcript of the call.

Mr. Cook went on to discuss in further detail Apple’s other forays into healthcare, before repeating his oft-stated belief that “there will be a day in the future that we look back and Apple’s greatest contribution will be to people’s health.”

https://www.beckershospitalreview.com/healthcare-information-technology/apple-reports-17-revenue-growth-led-by-54-surge-in-wearables.html

ICU Medical recalls 2 IV fluids

ICU Medical is recalling two intravenous fluids that were sent to hospitals nationwide.

The recall affects one lot of ICU Medical’s lactated ringer’s injection and one lot of its 0.9 percent sodium chloride injection. Both products replace losses of fluids or electrolytes in patients.

The recall was initiated after particulate matter was discovered in the injections.

ICU Medical said it has not received any adverse event reports.

https://www.beckershospitalreview.com/supply-chain/icu-medical-recalls-2-iv-fluids.html