Sanitation: A 'game changer' after kidney transplant

Health Rounds

By Nancy Lapid, Health Science Editor

Hello Health Rounds readers! Today we report on an experimental drug that could improve patients' lives after kidney transplant. We also highlight potentially important discoveries that could lead to the first treatment for West Nile virus, and improved care of pneumonia patients.

Ebola updates: Cases in Congo reach highest first-month total of any outbreak, WHO says, while construction of US-backed Ebola facility in Kenya is halted.

In other breaking news: US judge blocks Trump administration's SNAP restrictions on soda, candy; European patients' access to new drugs worsens, pharma lobby says; UNAIDS chief urges US to reconsider South Africa funding cut; and US FDA updates guidance to speed drug development.

Also: Ukraine's battlefield shift has not solved its humanitarian crisis; and climate-vulnerable countries push for global funding framework.

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US provides Ebola treatment for outbreak in Congo, bringing trials closer

REUTERS/Stringer/File Photo

The U.S. has provided doses of an experimental antibody drug from Mapp Biopharmaceutical for use in clinical trials to fight the widening Ebola outbreak in Democratic Republic of Congo, a shift from its position of making the drug available just for ‌Americans. Read more.

Study Rounds

A new immunosuppressant for kidney recipients

An experimental immunosuppressant drug being developed by Eledon Pharmaceuticals proved superior to the current standard treatment, according to data from a clinical trial, and looks to be a potential game-changer for kidney transplant patients.

Kidney recipients must take immunosuppressive drugs for their lifetime to prevent organ rejection. The medications can affect both long-term graft survival and how patients feel and function in their daily lives.

While the current standard-of-care immunosuppressant – tacrolimus, in use since the 1990s – basically affects the entire immune system, the Eledon drug, tegoprubart, selectively blocks the activation of specific immune cells in the so-called CD40L pathway.

In a long-term follow-up study of kidney transplant patients who participated in a 12-month mid-stage trial, those treated with tegoprubart had superior kidney function from one month onward compared with patients treated with tacrolimus, researchers reported at the American Transplant Congress in Boston.

Patients treated with tegoprubart had no graft loss and no biopsy-proven acute rejection episodes after the first six months post-transplant, compared with roughly 64% in the tacrolimus group.

Side effects were less common with tegoprubart as well. Just 2% of those who got the Eledon drug experienced headache or acute kidney injury versus 12% and 6% for tacrolimus, respectively. None of the patients taking the new drug had extremity pain, or falls or loss of balance, compared with 10% and 6% for the standard of care.

“For kidney transplant recipients, success is measured not only by preventing rejection, but by preserving kidney function and maintaining quality of life over the long term,” study leader Dr. Andrew Adams of the University of Minnesota said in a statement.

Eledon has said it plans to conduct a late-stage trial of tegoprubart in kidney recipients later this year.

In a separate presentation at the meeting, Dr. Nicole Wojcik from the University of Chicago reported on a pilot study in which tegoprubart was well-tolerated and effective in patients with diabetes undergoing pancreatic islet cell transplantation.

Developing protection against West Nile virus

Researchers are a step closer to developing a vaccine or a treatment for West Nile virus, the mosquito-transmitted disease that can cause severe brain infection and death.

Studying blood samples provided by survivors of the disease, the researchers identified antibodies that may help address this unmet medical need, according to a report published in Immunity.

Reproducing the antibodies in test tubes, they found that one, called W010, recognizes and attacks a protein on the virus envelope that helps it attach to and infect host cells.

Treatment with W010 protected mice when administered before and even five days after exposure to West Nile virus.

A second antibody, W014, was effective not only against West Nile virus but also against other orthoflaviviruses, including Japanese encephalitis, Murray Valley encephalitis, Saint Louis encephalitis and Usutu viruses.

The identification of these human antibodies – and the vulnerable sites they target on the viruses – will help guide “the development of medical countermeasures against severe diseases that... represent an important unmet medical need globally,” the researchers said.

Pneumonia discovery may improve treatment of severe cases

Severe pneumonia has three distinct subtypes with varying biological responses, a finding that helps explain why some patients recover quickly while in others the lung infection becomes fatal, researchers say.

On the surface, the 95 intensive-care-unit patients in the study appeared similarly ill, but their outcomes were very different, study leader Dr. Mark Jeffrey of the University of Cambridge said in a statement.

“It was only when we drilled down and looked at patterns of inflammation that the differences became apparent,” he said.

About half the patients mainly had immune-system suppression, significant damage to the lining of the lungs, and bleeding in the tiny air sacs in the lungs. These patients did not have many signs of inflammation, which may explain why anti-inflammatory medications can fail or even be harmful in some cases, the researchers reported in Nature Communications.

Another quarter of patients – those who were critically ill for the longest periods and spent the most time on mechanical ventilation - had severe and persistent inflammation, with a flood of immature immune cells in the lungs. They would be most likely to respond to anti-inflammatory treatments, the researchers said.

Finally, about a quarter of cases were characterized by a balanced immune response and active repair of damage to the lungs. These patients were most likely to recover faster and spend the shortest time on the ventilator, even though they initially appeared to be just as ill as the others.

“This helps explain why ‘one-size-fits-all’ treatments, including some immune-modulating drugs, have often failed in clinical trials,” Jeffrey said.

Senior study author Dr. Andrew Conway Morris of the University of Cambridge said failing to look at the disease's underlying biology risks missing important information.

“Instead of asking ‘Does this patient have pneumonia?’, we should be asking ‘What's the inflammatory pattern in this patient's lungs?’” Morris said.

Study coauthor Dr. Vilas Navapurkar from Addenbrooke's Hospital in Cambridge added, “If we know which subtype of pneumonia an individual has, we can potentially tailor their treatment more precisely, boosting the immune response in some, while calming harmful inflammation in others.”