Romark Alinia Adult Dose “Approvable”; Anti-Parasitic Approved For Children

Romark Labs' Alinia for treatment of intestinal parasites in adults could be approved by FDA as early as mid-2003 following receipt of an "approvable" letter Nov. 22, the company said.

FDA is requesting additional Alinia (nitazoxanide) studies of the adult tablet formulation. Romark Labs is seeking an indication for diarrhea caused by the Cryptosporidium parvum and Giardia lamblia parasites in patients over 18 years; the filing was granted a priority review.

Alinia oral suspension was cleared by FDA on Nov. 22 for the "treatment of diarrhea caused by Cryptosporidium parvum and Giardia lamblia in pediatric patients one through 11 years of age," ¹ Alinia labeling says (² 'The Pink Sheet' Nov. 25, In Brief).

Romark Labs will launch the pediatric oral suspension at the end of January after it begins manufacturing commercial lots at its facility in Bornem, Belgium. The anti-parasitic is approved for use in more than 100 countries.

Alinia is Romark's first FDA-approved product. The Tampa-based company will begin marketing Alinia in the U.S. on its own, but it is seeking a copromotion partner. Romark plans to build an internal sales force for Alinia, in addition to the potential outside team.

Romark discovered nitazoxanide and licensed the compound to Unimed in 1996 for development as a treatment of cryptosporidiosis diarrhea associated with AIDS, under the brandname Cryptaz .

Unimed filed a Cryptaz NDA but decided not to pursue development after FDA's Antiviral Drugs Advisory Committee suggested that a dose comparison study be conducted prior to approval (³ (Also see "Unimed Cryptaz Dose Comparison Study To Show Efficacy Suggested By Cmte." - Pink Sheet, 11 May, 1998.), p. 6). Unimed said the declining rate of the condition in AIDS patients would make enrollment difficult (⁴ (Also see "Unimed Cryptaz" - Pink Sheet, 18 May, 1998.), In Brief).

Romark re-acquired rights to the AIDS-related indication in 1998 and conducted the studies recommended by the advisory committee. The company filed for the indication at the end of September and received priority review; Romark expects approval in the first half of 2003.

The indications section of Alinia's pediatric labeling notes that the "safety and effectiveness of Alinia for Oral Suspension have not been established in HIV positive patients or patients with immunodeficiency."

The Cryptaz trade name was changed to Alinia to avoid confusion with GlaxoSmithKline's antibiotic Ceptaz (ceftazidime), Romark said.

Romark is pursuing a number of indications for Alinia, including treatment for diarrhea associated with the parasite Entamoeba histolytica (in Phase III) and two bacteria, Clostridium difficile and Helicobacter pylori (in Phase II).

Alinia is the only drug approved for cryptosporidiosis and the first for giardia in more than 40 years, Romark said. The Centers for Disease Control & Prevention estimates up to 2.5 mil. cases of diarrhea are caused by G. lamblia each year, and up to 20% of children are exposed to C. parvum by the time they are seven years old.

Alinia was approved based on two C. parvum studies in Egypt and Zambia and one G. lamblia study in Peru. In the 48-patient Egypt study, after a three-day course of nitazoxanide, 88% of patients had a clinical response within three to seven days, versus 38% of placebo patients. The Zambia study was conducted in malnourished children ages 12-35 months; 56% of patients on Alinia responded, versus 23% on placebo.

Another C. parvum study was conducted in Zambia in severely malnourished pediatric AIDS patients; Alinia "did not produce clinical cure rates that were significantly different from placebo," labeling says.

For giardia, a three-day course of Alinia was compared to five days metronidazole in a 110-patient study. After seven to 10 days of therapy, 85% of nitazoxanide patients had clinical responses, versus 80% of those on metronidazole, in an intent-to-treat population.

The most frequently reported adverse events among 613 HIV-negative Alinia patients were abdominal pain (7.8%), diarrhea (2.1%), vomiting (1.1%) and headache (1.1%), the adverse reactions section says. Labeling does not contain a warnings section.

The Alinia NDA (21-498) was filed May 29 and received a priority review. As a Phase IV commitment, Romark will conduct a pharmacokinetic study to look at the drug's effect with and without food.