FDA Approves New Indication for Envarsus XR (tacrolimus extended-release tablets)

In continuation of my update on Tacrolimus

Veloxis Pharmaceuticals announced today that the U.S. Food & Drug Administration (FDA) approved a new indication for Envarsus XR (tacrolimus extended-release tablets) to prevent organ rejection in de novo kidney transplant patients in combination with other immunosuppressants. This indication is commonly referred to as the de novo indication.

Envarsus XR was approved for the prophylaxis of organ rejection in kidney transplant patients converted from tacrolimus immediate-release formulations in 2015 and has already been used in the conversion setting in more than 90% of the transplant centers in the U.S.  The approval for de novo use provides an important new treatment option for kidney transplant patients and providers, where significant unmet need currently exists.

"Today marks the beginning of an exciting new chapter in immunosuppression.  Kidney transplant patients will now be able to receive a refined and simplified gold standard treatment regimen from the beginning of the kidney transplant journey," said Ulf Meier-Kriesche, M.D. Chief Scientific Officer at Veloxis Pharmaceuticals, Inc.

The FDA's approval is based on the Phase 3 clinical development program which was a randomized, double-blind, double-dummy, Phase III study in 543 de novo kidney transplant patients that demonstrated comparable efficacy and safety compared to twice-daily tacrolimus (Prograf®).

The primary endpoint of the study was a composite endpoint of treatment failure (biopsy-proven acute rejection or BPAR, graft failure, loss to follow up or death) that was evaluated after a 12-month treatment period to demonstrate the non-inferiority of Envarsus® compared to Prograf®. The treatment failure rate for Envarsus® was 18.3% compared to 19.6% for Prograf®.    

"There are approximately 200,000 patients living with a kidney transplant today and we have seen a significant number of them convert to Envarsus XR since our launch in December 2015.  With the addition of the de novo indication, the roughly 16,000 adult patients who receive a kidney transplant each year will now have access to Envarsus XR following surgery. This approval is another example of Veloxis's commitment to transplant and the patients, donors and providers that make it all possible," said Craig A. Collard, Chief Executive Officer of Veloxis Pharmaceuticals A/S.

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FDA Approves New Indication for Envarsus XR (tacrolimus extended-release tablets)

Sitagliptin Promising Addition for Preventing Acute GVHD

In continuation of my updates on sitagliptin 

For patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation, sitagliptin combined with tacrolimus and sirolimus results in a low incidence of grade II to IV acute graft-versus-host disease (GVHD) by day 100, according to a study published in the Jan. 7 issue of the New England Journal of Medicine.

Sherif S. Farag, M.D., Ph.D., from the Indiana University School of Medicine in Indianapolis, and colleagues conducted a phase 2 clinical trial to examine the reduction in incidence of grade II to IV acute GVHD from 30 percent to no more than 15 percent by day 100 with sitagliptin plus tacrolimus and sirolimus. Thirty-six patients received myeloablative conditioning followed by mobilized peripheral-blood stem cell transplants from matched related or unrelated donors.

The researchers found that by day 100, acute GVHD occurred in two of 36 patients. The incidence of grade II to IV GVHD and of grade III or IV GVHD was 5 and 3 percent, respectively. At one year, nonrelapse mortality was zero. The one-year cumulative incidence of relapse was 26 percent, and for chronic GVHD, it was 37 percent. At one year, GVHD-free, relapse-free survival was 46 percent. Toxic effects were similar to those seen in patients undergoing allogeneic stem cell transplantation.

"Inhibition of dipeptidyl peptidase 4 should be further investigated in randomized trials that compare sitagliptin with current standard GVHD prophylaxis regimens," the authors write.

https://en.wikipedia.org/wiki/Sitagliptin

Envarsus XR granted FDA orphan drug designation for prophylaxis of organ rejection in kidney transplant patients

Veloxis Pharmaceuticals A/S (OMX: VELO), today announced that Envarsus^® XR was     granted Orphan Drug status by the U.S. Food and Drug Administration(FDA) for prophylaxis of organ rejection in patients who convert fromimmediate-release tacrolimus. Envarsus^® XR received marketing authorization from the FDA on July 10, 2015.

"We view Orphan Drug status as the FDA's recognition of thedifferentiated profile and the unique 'switch' indication of Envarsus^® XR compared  to  other               tacrolimus products," said William Polvino, M.D.,
president and chief executive officer of Veloxis. "We now look forwardto making Envarsus^® XR available to conversion patients by the end of 2015."

Orphan drug designation is designed is to encourage the developmentof drugs that may provide significant benefit to patients suffering from rare diseases. The designation is granted by the FDA upon recognition
that the prevalence of the U.S. target patient population is 200,000patients or less. Orphan drug designation entitles Veloxis to a waiver of the FDA prescription drug user fees for Envarsus^® XR aswell as for potential tax incentives. Additionally, U.S. dataexclusivity protection may be extended for up to seven years.

 

Envarsus XR granted FDA orphan drug designation for prophylaxis of organ rejection in kidney transplant patients

Antifungal drug resistance evoked through RNAi-dependent epimutations

Microorganisms like bacteria and fungi can evade treatment by acquiring mutations in the genes targeted by antibiotics or antifungal drugs. These permanent mutations were once thought to be the only way for drug-resistant strains to evolve. Now a new study has shown that microorganisms can use a temporary silencing of drug targets -- known as epimutations -- to gain the benefits of drug resistance without the commitment.

Though the new mechanism was discovered in a fungus called Mucor circinelloides, it is likely to be employed by other fungi as well as bacteria, viruses and other organisms to withstand treatment with various drugs. The finding appears July 27, 2014, in Nature.

"This mechanism gives the organism more flexibility," said Joseph Heitman, M.D., Ph.D., senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine. "A classic, Mendelian mutation is a more permanent binding decision, like a traditional marriage. These epimutations are reversible, more akin to moving in together. If conditions change, it is easier to revert to the way things were."

The epimutations are so transient, in fact, that the researchers almost disregarded them. Cecelia Wall, a graduate student in Drs. Heitman and Maria Cardenas' labs, had been looking for mutations that would make the human fungal pathogen M. circinelloides resistant to the antifungal drug FK506 (also known as tacrolimus). This pathogen causes the rare but lethal fungal infection mucormycosis, an emerging infectious disease that predominantly affects individuals with weakened immune systems.

Ref:http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13575.html

Antifungal drug resistance evoked through RNAi-dependent epimutations