New Study Reports Two Thirds Of Renal Recipients Switched To myfortic(R) Experience An Improvement In Gastrointestinal Symptom Burden

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Transplants / Organ Donations
Article Date: 20 Dec 2007 - 2:00 PDT

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A large-scale open label non-comparative study published this week in Transplantation demonstrates that, following conversion from mycophenolate mofetil therapy (MMF) to myfortic(R) (mycophenolic acid) delayed-release tablets, gastrointestinal (GI) complaints in kidney recipients are improved and sustained over the three month trial1.

Up to 45 percent of recipients experience GI side effects with MMF2. These side effects are often managed by reducing the dose of MMF or withdrawing MMF treatment. Reducing MMF treatment has been shown to lead to an eight-fold increase in the incidence of acute rejection episodes in the first year following renal transplant3.

"Gastrointestinal side effects are common post transplant in recipients receiving immunosuppressive therapy," said Dr Paul Bolin of the Division of Nephrology and Hypertension, Brody School of Medicine at East Carolina University and lead study author. "This study showed that recipients switched to myfortic reported reduced symptoms."

The three month study was carried out in multiple centers in the US and involved 728 adult renal transplant recipients receiving MMF. Recipients self-reported changes in their GI symptom burden using the self-administered GSRS questionnaire, which is designed to assess the symptoms associated with common GI disorders. Physicians rated their symptom severity using standard adverse event reporting procedures. These tools are often used in clinical settings to evaluate GI complaints.

A significant overall improvement in GSRS score was seen from baseline to month one and was sustained to month three. Two thirds (66 percent) of recipients considered that their GI symptoms had improved compared to baseline three months after conversion to myfortic. This was consistent with physicians' ratings of overall treatment effect. Reductions in symptom burden were seen in all types of GI complication, with the greatest reductions seen in diarrhea and indigestion1.

The study included recipients receiving MMF in combination with either of the calcineurin inhibitors (cyclosporine or tacrolimus), both of which act to suppress the immune system. Conversion to myfortic benefitted both groups of recipients with significant improvements in GSRS score.

The length of time since transplantation did not affect the extent to which conversion to myfortic improved gastrointestinal symptoms. The benefits of conversion to myfortic were equally apparent in recipients of African-American origin and non-African Americans. Recipients with diabetes obtained similar benefit from conversion as those who were diabetes-free1.

Non-GI complications were reported by 45 percent of recipients; the majority of complications were mild or moderate. However, 19.2 percent of recipients experienced GI and non-GI adverse events with a suspected relation with myfortic. Conversion from MMF to myfortic did not appear to comprise efficacy or overall safety1.

About myfortic

myfortic (mycophenolic acid) delayed-release tablet is indicated for the prophylaxis of organ rejection in recipients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.

The FDA's approval in 2004 of myfortic was based on two randomized, multi-center, double-blind pivotal clinical trials of more than 700 de novo (newly transplanted) and maintenance renal transplant recipients, demonstrating effective graft protection together with a good safety profile4,5. In the de novo study, at both the six- and 12-month timepoints, therapeutic equivalence in terms of efficacy, safety and tolerability versus MMF was demonstrated. In the maintenance recipients study, recipients who were converted from initial treatment with MMF to myfortic had comparable safety to recipients who remained on MMF at six- and 12-month timepoints, without compromising efficacy.

Immunosuppression may lead to increased susceptibility to infection and possible development of lymphoma and other neoplasms. Only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should use myfortic. Recipients receiving myfortic should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the recipient. Female recipients of childbearing potential must use contraception. Use of myfortic during pregnancy is associated with increased risks of pregnancy loss and congenital malformations.

Recipients receiving immunosuppressive regimens involving combinations of drugs, including myfortic as part of an immunosuppressive regimen are at increased risk of developing lymphomas and other malignancies, particularly of the skin.

Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections, fatal infections, and sepsis.

myfortic (mycophenolic acid) can cause fetal harm when administered to a pregnant woman. A recipient who is planning a pregnancy should not use myfortic unless she cannot be successfully treated with other immunosuppressant drugs. Risks and benefits of myfortic and alternative immunosuppressants should be discussed with the recipient. If this drug is used during pregnancy, or if the recipient becomes pregnant while taking this drug, the recipient should be apprised of the potential hazard to the fetus.

Women of childbearing potential (including pubertal girls and peri-menopausal women) taking myfortic must receive contraceptive counseling and use effective contraception. The recipient should begin using her two chosen contraceptive methods 4 weeks prior to starting myfortic therapy, unless abstinence is the chosen method. She should continue contraceptive use during therapy and for 6 weeks after stopping myfortic. Recipients should be aware that myfortic reduces blood levels of the hormones in the oral contraceptive pill and could theoretically reduce its effectiveness. Recipients receiving myfortic should be monitored for neutropenia. If neutropenia develops (ANC < 1.3 x 103/-L), dosing with myfortic should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the recipient managed appropriately (see Dosage And Administration section of the myfortic Prescribing Information).

Gastrointestinal bleeding (requiring hospitalization) has been reported in de novo renal transplant recipients (1.0 percent) and maintenance recipients (1.3 percent) treated with myfortic (mycophenolic acid) (up to 12 months). Common adverse events reported in 20 percent of recipients receiving myfortic or MMF in the 12-months de novo renal study and maintenance renal study, when used in combination with cyclosporine, USP (MODIFIED) and corticosteroids, are listed in Table 4 of the Adverse Reactions section of the myfortic Prescribing Information.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as "may," or similar expressions, or by express or implied discussions regarding potential future sales of myfortic, or regarding the long-term impact of a patient's use of myfortic. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with myfortic to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that myfortic will reach any particular sales levels. Neither can there be any guarantee regarding the long-term impact of a patient's use of myfortic. In particular, management's expectations regarding myfortic could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data, and unexpected additional analysis of existing myfortic clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; increased government, industry, and general public pricing pressures; and other risks and factors referred to in the Company's current Form 20-F on file with the U.S. Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, gastrointestinal and respiratory areas. The company's mission is to improve people's lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS), a world leader in offering medicines to protect health, treat disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. Novartis is the only company with leadership positions in both patented and generic pharmaceuticals. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. In 2005, the Group's businesses achieved net sales of USD 32.2 billion and net income of USD 6.1 billion. Approximately USD 4.8 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 96,000 people and operate in over 140 countries around the world. For more information, please visit http://www.novartis.com.

References

1. Bolin P, Tanriover B, Zibari G et al. Improvement in 3-month reported gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant patients. Transplantation 2007;84(11), 1443-1451

2. Tierce JC, Porterfield-Baxa J, Petrilla AA et al. Impact of mycophenolate mofetil (MMF)-related gastrointestinal complications and MMF dose alterations on transplant outcomes and healthcare costs in renal transplant recipients. Clin Transplant 2005; 19:779-784

3. Pelletier R, Akin B, Henry ML et al. The impact of mycophenolate mofetil dosing patterns on clinical outcome after renal transplantation. Clinical Transplantation 2003; 17: 200-205

4. Salvadori M, Holzer H, de Mattos A et al. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant. 2004;4:231-236.

5. Budde K, Curtis J, Knoll G et al. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant. 2004;4:237-243.

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