On their way to the European market with Elelyso, Pfizer Inc. and Protalix BioTherapeutics Inc. tripped over Shire plc's marketing exclusivity for Vpriv.

Citing the 10-year orphan exclusivity awarded Shire's Gaucher disease drug, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended against marketing authorization for Elelyso (taliglucerase alfa), even though it acknowledged the drug has a positive risk-benefit profile.

As a result, shares of Camiel, Israel-based Protalix (NYSE:PLX) opened at $5.57 Friday, down nearly 16 percent from Thursday's close of $6.60. They quickly bounced back above the $6 mark in heavy trading, closing at $6. 14 Friday.

Protalix and Pfizer were aware of Shire's exclusivity, granted in August 2010, but they thought there was a clear path around it because of recent shortages and the possibility of offering Elelyso at a discounted price. "This is a very unique situation," Protalix President and CEO David Aviezer said in an investors' call, adding that Vpriv (velaglucerase alfa) – despite its orphan exclusivity – was not the first drug on the European market for Type I Gaucher disease.

The European Commission (EC) is expected to make a final decision within three months. Although the EC usually goes along with CHMP's opinions, Protalix and Pfizer plan to do whatever they can to reverse the negative recommendation for their enzyme replacement therapy. One possibility would be to show superiority.

"From a commercial standpoint, this is absolutely a setback we'll need to address," Aviezer said.

Wells Fargo senior analyst Brian Abrahams agreed, saying Europe is a significant market for Elelyso, as nearly 40 percent of its projected outyear sales were expected to be from Europe.

In light of CHMP's opinion, the likelihood of European approval is much lower. "Although given the unusual circumstances, it is still possible EMA could allow Elelyso to be marketed," Abrahams said.

Meanwhile, Protalix and Pfizer, of New York, will move forward with marketing applications for Elelyso in Australia, Brazil, Israel and several other countries, Aviezer said.

Elelyso got FDA approval in May as the first plant cell-based enzyme replacement therapy for Gaucher disease. It also was the first FDA-approved plant cell-expressed drug derived from Protalix's manufacturing system, ProCellEx. (See BioWorld Today, May 3, 2012.)

Besides Vpriv, Elelyso competes with Cerezyme (imiglucerase, Sanofi SA) in the U.S.

Protalix and Pfizer signed a $115 million profit-sharing deal in 2009 to develop and commercialize taliglucerase alfa, then called Uplyso. Protalix retained exclusive commercialization rights in Israel, while Pfizer received exclusive licensing rights to commercialize the drug elsewhere. (See BioWorld Today, Dec. 2, 2009.)

European regulators also weighed in on several other marketing applications last week:

• Sanofi Pasteur, the vaccines division of Paris-based Sanofi SA, said its Hexaxim (DTaP-IPV-Hib-HepB vaccine) received a positive opinion from the EMA as part of a procedure to evaluate medical products intended for markets outside the European Union. This is the first time the EMA has followed the procedure for a vaccine. Several countries in Africa, Asia, Latin America and the Middle East grant market authorization based on the EMA's scientific opinions. Hexaxim is a ready-to-use liquid vaccine that protects infants against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae Type b.

• Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, and AMAG Pharmaceuticals Inc., of Lexington, Mass., reported that the EC granted marketing authorization for Rienso (ferumoxytol), an intravenous iron therapy to treat iron deficiency anemia in adult patients with chronic kidney disease. The authorization follows a positive CHMP opinion issued in April. Takeda plans to launch Rienso across Europe in the near future. Developed by AMAG, ferumoxytol is approved for use in Canada and the U.S. as Feraheme and marketed outside the U.S. by Takeda under a 2010 co-marketing agreement. The approval sent AMAG shares (NASDAQ:AMAG) up 61 cents, to close at $15.05 Friday. (See BioWorld Today, April 2, 2010.)

• Takeda also received good news on its marketing application for Revestive (teduglutide), with CHMP recommending approval of the recombinant analogue of glucagon-like peptide 2 for the treatment of adult patients with short bowel syndrome. Revestive has orphan status as there is no treatment currently approved in Europe for the rare, debilitating condition. Takeda obtained ex-North American rights to Revestive in its acquisition last year of Nycomed GmbH, which had licensed it from NPS Pharmaceuticals Inc., of Bedminster, N.J. Shares of NPS (NASDAQ:NPSP), which is developing teduglutide as Gattex in the U.S., were up $1.01 Friday, or 14 percent, closing at $8.21. (See BioWorld Today, May 20, 2011.)