Tag Archives: Pharma

New treatment against transplantation complications tested – Medical News Today

Last updated: 4 September 2014 at 2am PST

A class of biotechnology drugs called monoclonal antibodies is now being tested in clinical studies to treat an unmet medical need post-transplantation, called delayed graft function

It is not uncommon for kidney transplants to fail. Once transplanted, the kidney must connect back with the blood supply to start working properly and be truly accepted by the body. Delays can cause complications. An example, known as delayed graft function (DGF), is where the new kidney can become inflamed while starved of blood supply. This serious complication affects over half of those who receive kidneys from deceased donors.

Now, a solution may be in sight. A new drug candidate, belonging to the family of monoclonal antibodies, called OPN-305 is capable of dampening down the body’s immune response to a donated kidney. Developed since 2005 by a biopharmaceutical company in Dublin, Ireland, called Opsona Therapeutics, studies have confirmed that it works in animals and is not toxic. An initial clinical trial in healthy humans, referred to as phase I study, has shown it is safe. Now, as part of the EU-funded project MABSOT, the drug will be tested on a number of patients. This will be a proof-of-concept, so-called Phase II, clinical trial.

“There are huge health benefits and economic benefits for people if this candidate actually works. There is nothing approved for DGF, so this would greatly improve the quality of life for people who would ultimately end up on dialysis,” says project coordinator Mary Reilly, vice president of Pharmaceutical Development and Operations at Opsona Therapeutics.

Inflammation is caused by the immune response. Proteins called Toll-like receptors recognise invading microbes and sets off the body’s defences. But OPN-305 binds this key receptor and stops it from triggering the body’s immune system. “The OPN-305 antibody binds to Toll-like receptor 2 (TLR2) and effectively switches off the signal that provokes inflammation,” explains Reilly. “The inflammation that it reduces is a major cause of poor kidney function immediately after transplantation,” she tells youris.com.

To assist in the development of OPN-305 it was granted orphan drug status. This means the regulator giving it some incentives in recognition of its importance to treat unmet medical needs. Indeed, there are no other treatments for DGF. “This particular compound has the potential to be the first and best in class,” says Reilly. “There is nothing else out there for this disease, so it could really transform people’s quality of life.” However, tests for its effectiveness and safety remain just as stringent as for any drug.

For this trial, OPN-305 will be given to organ recipients on top of the existing standard treatment. Altogether, 50 medical centres in the US and in Europe will be involved in this Phase II trial, with 270 patients opting to be involved. “If Phase II is successful, the next step will be to move to a Phase III clinical study. This is a larger clinical study with a more mixed population,” Reilly explains. The Phase III trial is the final hurdle in an approval process that can take 10 years or more alltogether.

One expert believes the project is quite challenging. “In this project they humanised a mouse monoclonal antibody. So they took its mouse amino acids and changed them to be like human amino acids. We call that humanising the antibody and it is quite challenging,” comments Dr Pierre Lafaye, head of antibody engineering at the Institut Pasteur, in France.

And there could be unforeseen effects. “It could trigger a secondary effect not observed in vitro or in mice. So sometimes that could be a headache or fever or something like that. At the biological level there are differences between a mouse model and human, so I think this is quite an interesting project. But in clinical development you never know if it is going to reach a successful end,” Lafaye tells youis.com.

Lafaye says that monoclonal antibodies have had a major impact in the field of cancer therapy. But not so much in autoimmune diseases. Asked about alternative strategies for organ transplants, he says: “A small chemical compound that is able to interact with TLR-2 could work, but these small compounds usually have a short half-life [which means that they do not necessarily stay long enough in the body to be effective]. Monoclonal antibodies have half-lives of several days.” This means they hang around in the body for longer – a half-life is the time it takes for half of a given compound to be broken down.

Another expert believes the approach is promising. “Monoclonal antibodies have been used in some autoimmune conditions such as rheumatoid arthritis,” says Anne Cooke, a professor of immunology at the University of Cambridge, UK. “TNF blockers such as the drug Infliximab and B-cell depleters such as the drug Rituximab have been used in rheumatoid arthritis (RA). TNF blockers have been life-changing, having terrific results in a good proportion of RA patients,” she tells youris.com. Asked about advantages of using monoclonal antibodies, she notes “perhaps increased specificity over more generalised immune suppression.” This means that antibodies are more preferentially targeted and this should therefore produce fewer side effects.

via New treatment against transplantation complications tested – Medical News Today.

Tocilizumab Research Could Lead to Personalized Treatments for Kidney Transplant Patients

Eileen Oldfield, Associate Editor

Published Online: Saturday, August 9, 2014

A multicenter study will examine whether a drug used to treat rheumatoid arthritis can improve kidney transplant patients’ health.

Researchers from several medical centers will use rheumatoid arthritis drug tocilizumab in a study to determine whether the drug improves kidney transplant patients’ long-term survival. The study will include 2 clinical trials.

The research focuses on regulatory T cells (Tregs), lymphocytes that suppress activity in other immune cells, a press release from the University of California, San Francisco, stated. Normally, Tregs maintain the immune system’s normal homeostasis and safeguard against autoimmune diseases. Researchers hope to induce long-term donor-specific tolerance without impeding immune response to pathogens and tumors in transplant patients.

Preclinical studies show that the cells can be used to control responses in graft-versus-host disease; however, additional research on Treg reactivity, dosing, adjunct immunosuppression, and infusion timing is needed.

The goal is to control inflammation in kidney transplant recipients by increasing the number or activity of Tregs by either infusing the cells into the body or by using tocilizumab to block the inflammatory effects of interleukin 6, the press release stated.

The results of small patient studies suggest a significant, sustained increase in Tregs following tocilizumab treatment, leading to the theory that the drug will increase Treg population in patients who received kidney transplants.

The National Institutes of Health will fund this 7-year, $17-million study investigating the therapy. In addition to the University of California, San Francisco, the University of Alabama at Birmingham, Emory University, and Cedars-Sinai Medical Center will participate in the research.

Although transplantation advances have reduced early acute rejection rates and improved 1-year graft survival, long-term graft success rates remain unchanged. The reasons for the flat long-term success rates include interstitial fibrosis progression and tubular atrophy in the kidney.

According to principal investigator Flavio Vincenti, MD, UCSF professor of medicine, the research holds the promise of personalized treatments for transplant patients.

“This grant allows us to work toward achieving 2 important advances in the transplant field,” Dr. Vincenti said. “We can introduce personalized medicine by treating patients based on molecular profiling of their kidney. We also can allow control of the response to the transplant by the patient’s own immune systems by regulatory T cells, either through infusions or pharmacologically.”

via Tocilizumab Research Could Lead to Personalized Treatments for Kidney Transplant Patients.

Company agrees to $35-million settlement over kidney transplant – 21 News Now, More Local News for Youngstown, Ohio –

Company agrees to $35-million settlement over kidney transplant drug

Posted: Aug 06, 2014 9:34 AM

Updated: Aug 06, 2014 9:42 AM


Ohio Attorney General Mike DeWine has announced that Ohio and 41 other attorneys general have reached a $35 million settlement to resolve allegations that Wyeth Pharmaceuticals Inc. unlawfully promoted Rapamune, a drug approved for use by kidney transplant patients. Pfizer Inc., the parent company of Wyeth, agrees to be bound by the settlement.

Ohio will receive $984,812 as part of the settlement.

Rapamune is currently approved by the U.S. Food and Drug Administration (FDA) to prevent the body from rejecting an organ after kidney transplant surgery.

The attorneys general allege that Wyeth violated state consumer protection laws by misrepresenting the uses and benefits of Rapamune, relating to: (1) unapproved use following an organ transplant other than a kidney transplant; (2) unapproved protocol of converting patients to Rapamune after they first received a different immunosuppressive drug; and (3) use in unapproved drug combinations.

Today’s proposed settlement, which must be approved by the court, requires Pfizer to ensure that its marketing and promotional practices do not unlawfully promote Rapamune or any Pfizer product.

Specifically, Pfizer shall not:

Make, or cause to be made, any written or oral claim that is false, misleading, or deceptive regarding any Pfizer product;

Make any claim comparing the safety or effectiveness of a Pfizer product to another product when that claim is not supported by substantial evidence as defined by federal law and regulations;

Promote any Pfizer product for off-label uses;

Include mechanisms in its financial incentives to provide incentive compensation for sales that may be attributable to the off-label uses of any Pfizer product;

Affirmatively seek the inclusion of Rapamune in hospital protocols or standing orders unless Rapamune has been approved by the FDA for the indication for which it is to be included in the protocol or standing order;

Disseminate information describing any off-label or unapproved use of Rapamune unless such information and materials comply with applicable FDA regulations and the recommended actions in FDA Guidances for Industry; or

Seek to influence the prescribing of Rapamune in hospitals or transplant centers in any manner (including through funding clinical trials) that does not comply with the federal anti-kickback statute.

In Ohio, a complaint was filed and a proposed judgment order was submitted today to the Franklin County Common Pleas Court..

via Company agrees to $35-million settlement over kidney transplant – 21 News Now, More Local News for Youngstown, Ohio –.

Protein May Prevent Antibody-Mediated Transplant Rejection

Thu, 07/31/2014 – 8:40am

A study presented at the 2014 World Transplant Congress evaluated the safety and efficacy of CSL Behring’s C1 Inhibitor (C1-INH) concentrate in preventing antibody-mediated rejection following kidney transplants in highly sensitized patients. C1-INH is a human protein and an important inhibitor of the complement system.

The study shows that post-transplant treatment with C1-INH results in significant increases in the levels of complement components 3 and 4, suggesting that C1-INH inhibits activation of the complement system following transplantation. Antibody-mediated rejection is a major cause of kidney transplant failure and is often associated with activation of complement, a set of proteins that work with antibodies and play a role in the development of inflammation and tissue damage.

“Antibody-mediated rejection is a severe form of rejection that can occur in patients who have undergone a kidney transplant,” said Stanley Jordan, M.D., Kidney Transplant, Cedars-Sinai Medical Center in Los Angeles, and one of the study’s investigators. “Our findings provide additional insight into how C1-INH affects complement activation and represent an important advance in the study of complement-targeting therapeutics.”

The placebo-controlled, single-center study evaluated 20 highly sensitized patients, meaning they already had antibodies against donor organs. Subjects were randomized to receive either placebo or 20 IU/kg of C1-INH, administered intra-operatively, then twice a week for seven additional doses. Patients were desensitized with immunoglobulin and rituximab, decreasing the patient’s antibody levels prior to transplant.

According to study findings, fewer patients who were administered C1-INH developed serious adverse events compared to those administered placebo (20% versus 30%). C1-INH function and antigen levels in blood increased with C1-INH treatment [C1 function (p=0.0007) and C1-INH antigen percent (p=0.013)]. Patients treated with C1-INH experienced increased C3 levels on day 30 (p=0.005), while C4 levels were significantly higher at all time points. During the study period, no patient treated with C1-INH developed antibody-mediated rejection. Twenty percent of patients developed antibody-mediated rejection following the study period. Thirty percent of patients treated with placebo developed antibody-mediated rejection, 10% during the study period.

Date: July 30, 2014

Source: CSL Behring

via Protein May Prevent Antibody-Mediated Transplant Rejection.