New FDA Orphan Drugs: VariZIG, Pafuramidine Maleate, RG1068

Yael Waknine

December 08, 2006

December 8, 2006 — The US Food and Drug Administration (FDA) has granted orphan drug status for varicella zoster immune globulin [human] injection in the passive immunization of exposed, susceptible individuals who are at risk for complications from varicella; pafuramidine maleate for the treatment of Pneumocystis jiroveci pneumonia; and synthetic human secretin in diagnostic magnetic resonance imaging of the pancreas.

Orphan Drug Status for Varicella Zoster Immune Globulin Injection (VariZIG) for Those at Risk for Complications

On November 7, the FDA granted orphan drug designation for varicella zoster immune globulin [human] injection ( VariZIG, made by Cangene Corporation) in the passive immunization of exposed, susceptible individuals who are at risk for complications from varicella.

Those considered at risk include immunocompromised pediatric and adult patients, neonates, preterm infants, pregnant women, and newborns whose mothers had varicella zoster infection within 5 days before delivery or 2 days postdelivery.

For maximum benefit, the hyperimmune product should be administered as soon as possible after exposure. Efficacy of treatment administered more than 96 hours after exposure is uncertain and a 400-mg/kg dose of intravenous immune globulin should be considered as an alternative ( VZIG, made by Massachusetts Public Health Biologic Laboratories).

Pregnant women who do not receive postexposure prophylaxis with varicella immune globulin or intravenous immune globulin should be closely monitored for signs and symptoms of varicella and treated with acyclovir if indicated.

Because use of the varicella zoster immune globulin product can prolong the incubation period by more than a week, patients should be observed closely for signs and symptoms of varicella for 28 days after exposure and treated immediately with antiviral agents if indicated. Unless contraindicated, patients should receive varicella vaccine 5 months after immune globulin administration. Vaccine administration is not required in patients who develop varicella.

Varicella immune globulin is supplied as a lyophilized powder in 125-unit vials. Reconstitution with the accompanying sterile diluent forms a solution of 5% immunoglobulin class G antivaricella antibodies for intramuscular injection.

The recommended dose is 125 units/10 kg of body weight to a maximum of 625 units (5 vials). Infants weighing 10 kg or less should receive a minimum dose of 125 units (1 vial) regardless of weight.

The product is available in the United States via an expanded-access investigational new drug protocol previously approved by the FDA in January 2006. Healthcare providers wishing to register with the program may contact the company by telephone at 1-800-843-7477 or online at .

Varicella zoster immune globulin [human] injection was previously approved in Canada for intravenous or intramuscular administration to prevent or reduce the severity of maternal infections when given within 4 days of exposure to the varicella zoster virus.

Orphan Drug Status for Pafuramidine Maleate in the Treatment of PJP

On November 21, the FDA granted orphan drug designation for pafuramidine maleate (made by Immtech Pharmaceuticals, Inc) in the treatment of Pneumocystis jiroveci pneumonia (PJP, formerly known as Pneumocystis carinii pneumonia).

PJP is a fungal lung infection that usually occurs in immunocompromised patients, such as those who are infected with HIV, have progressed to AIDS, have other autoimmune disorders, are receiving cancer chemotherapy, or are recipients of solid organ transplants.

Although trimethoprim-sulfamethoxazole (TMP-SMX) is currently the highly effective gold standard for treatment, 20% to 50% of patients are unable to complete a course of therapy due to adverse events (some of which can be life-threatening) and are switched to other medications that are limited in efficacy and/or by adverse events. PJP resistance and subsequent treatment failure have also been reported.

According to a company news release, previous clinical research data have indicated that pafuramidine could have similar efficacy to TMP-SMX in PJP, but with fewer and less severe adverse effects.

In a phase 2 clinical trial, a 21-day course of pafuramidine was shown to resolve all clinical signs and symptoms of PJP in 32 Peruvian AIDS patients who were intolerant or resistant to TMP-SMX; no significant adverse events were reported.

In March 2006, a phase 3, double-blind, randomized, noninferiority trial was initiated at multiple sites in the United States and in Latin America, with the objective of showing that pafuramidine has similar efficacy and tolerability to TMP-SMX in HIV/AIDS patients with PJP.

The expected total enrollment is 270 patients who will be randomized to receive either pafuramidine twice daily (200 mg/day) for 14 days or TMP-SMX 3 times daily (4300 - 5800 mg/day) for 21 days. Patients will be monitored to assess clinical success at the end of the treatment period (day 22) and for an additional 3 weeks after therapy to assess sustained clinical success at day 42 of the study. Safety and tolerability of the study drugs will be assessed periodically throughout the 6-week study.

Other potential indications for the product currently under investigation include the treatment of malaria and African sleeping sickness.

Synthetic Human Secretin (RG1068) Granted Orphan Drug Status for Use in Pancreatic MRI

In November, the FDA granted orphan drug status for synthetic human secretin ( RG1068, made by Repligen Corporation) in diagnostic magnetic resonance imaging (MRI) of the pancreas.

Although secretin is often used by gastroenterologists in combination with endoscopy to evaluate and treat gallbladder and pancreatic diseases, the inherent risks associated with the invasive procedure may be avoided through use of MRI.

According to a news release, the company is currently conducting a multicenter, phase 2/3 clinical trial of the agent to assess its ability to improve detection of pancreatic duct structural abnormalities during MRI. It is also conducting a phase 1 investigational study to assess the agent's utility for functional imaging of the pancreas.


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