Elelyso: A New Therapeutic Option for Patients with Gaucher Disease

On May 1, 2012, the FDA approved Protalix BioTherapeutic’s Elelyso (taliglucerase alfa), a new enzyme replacement therapy (ERT) that provides patients with Gaucher disease an alternative therapeutic option to Genzyme’s Cerezyme (imiglucerase), the current market leader and standard of care in Gaucher disease, and Shire’s Vpriv (velaglucerase alfa).

Elelyso is the first ERT that is manufactured using a plant cell-based process, and the drug’s lower pricing as compared to both Cerezyme and Vpriv has been attributed to reduced costs associated with the plant cell production platform.

Elelyso was developed and is now being promoted through a partnership between Protalix and Pfizer. The FDA and the EMA both granted Elelyso orphan drug status.

The FDA also initially granted Elelyso fast-track development status, and a pivotal Phase III clinical trial, which served as the basis for the NDA submission, was completed in September 2009.

Elelyso and Vpriv were both approved for early access programs for patients requiring ERT during the global shortage of Cerezyme between 2009 and 2010, which resulted from a viral contamination incident at Genzyme’s Allston Landing facility in Massachusetts.

Development of Elelyso
Elelyso is a human recombinant glucocerebrosidase enzyme that is expressed using plant cells - specifically carrots - rather than mammalian cells. This is in contrast to Cerezyme and Vpriv, which are expressed using Chinese hamster ovary (CHO) cells and a human fibroblast cell line respectively.

Elelyso has the same core amino acid sequence as Cerezyme and a comparable homologous 3-dimensional structure, physical properties which clearly highlight its biosimilarity to Cerezyme.

The proprietary plant cell-based platform developed by Protalix has certain unique features that offer potential production, cost, and safety advantages over conventional mammalian cell-based human protein expression systems.

Known as ProCellEx, this system does not require a significant investment in capital and labor, and it is not dependent on large-volume bioreactors. Rather, the recombinant carrot cells used to express the human protein are cultured in disposable 800-liter plastic bags.

In addition, because the plant cell production platform does not involve any mammalian or animal components, or transgenic plants, safety risks such as exposure to mammalian viral infections are mitigated.

At launch, Elelyso was priced at $150,000 for a year of therapy, which is 25% lower than Cerezyme’s $200,000 price tag. Elelyso also costs less than Shire’s Vpriv, which was launched in 2010 at a price of $170,000 per patient per year.

Clinical Studies Supporting the Efficacy and Safety of Elelyso in Gaucher Disease
Despite two PDUFA delays, GlobalData predicted that Elelyso would be approved by the FDA, which proved to be accurate. These delays stemmed from the FDA’s request for additional clinical information from Protalix that related primarily to the presentation of select data that was already provided in the Elelyso NDA; there were no efficacy or safety concerns associated with the product.

GlobalData’s prediction that Elelyso would be approved was based on the positive efficacy and safety results of two clinical studies: the 2009 pivotal Phase III study, which included a 15-month, follow-on extension study, and a nine-month switchover study that was conducted during the global shortage of Cerezyme. In the first Phase III study, Elelyso met both the primary and secondary endpoints, and was shown to be safe and well tolerated.

Patients in the 15-month follow-on extension study demonstrated continued positive efficacy and safety results with Elelyso. The nine-month switchover study, which compared the efficacy and safety of Elelyso to that of Cerezyme, showed that patients who switched from Cerezyme to Elelyso remained stable.

Supply Continuity and Personal Support Programs for Elelyso
In view of the Cerezyme supply disruptions, which have affected patients with Gaucher disease throughout the world since 2009, Pfizer is launching the “Supply Continuity Program”.

This program is intended to minimize the possibility of any disruptions in the supply of Elelyso. As part of the program Pfizer will maintain a continuously restocked 24-months’ supply at various stages of production for patients in the US who are prescribed Elelyso.

According to the latest information from Genzyme, the production of Cerezyme has been restored to adequate levels to supply patients in the US, but not to satisfy patients in Europe and the rest of the world.

Pfizer is also introducing Gaucher Personal Support (GPS), a specialized program that provides support and specialty pharmacy services for patients who are prescribed Elelyso and their families.

Through GPS, Pfizer will cover 100% of prescription co-pay expenses for eligible patients on Elelyso who have commercial health insurance. In addition, Pfizer will provide financial assistance for eligible patients who are uninsured or underinsured, where allowed by law.

Marketing Strategies
From a commercial perspective, Protalix has put several key preapproval strategies in place that will allow the company to aggressively market Elelyso worldwide and enhance patient access. First, Protalix has partnered with Pfizer for the exclusive worldwide commercialization of the drug, except in Israel, where Protalix retained exclusive rights.

In addition, Protalix has filed a marketing authorization application for Elelyso in the EU, and has also submitted marketing applications for the drug in Israel, Australia, and Brazil. Additional regulatory applications are in progress worldwide.

Conclusions
GlobalData predicts that Elelyso will increase competition in the Gaucher disease therapeutics market, which is currently weak. Elelyso will likely capture a share of the market based solely on the fact that it is priced lower than Cerezyme and Vpriv.

However, GlobalData does not anticipate that Elelyso will displace Cerezyme as the market leader in Gaucher disease, in view of Genzyme’s longstanding reputation as the innovator of ERT for Gaucher’s and other lysosomal storage diseases.

Patients who began taking Elelyso during the global Cerezyme shortage may continue to do so simply because they and their physicians have become comfortable with the product and do not wish to go back to using Cerezyme, regardless of the contamination incident.

However, Vpriv was also used during the global Cerezyme shortage, which may limit the ability of Elelyso to gain market share from Vpriv. Thus, in this indication, factors such as patient and physician preference for a familiar treatment may prove more important than price.

Ultimately, the state of competition in the Gaucher disease treatment market makes it unlikely that Elelyso will be a significant revenue generator for Protalix.

The larger significance of the Elelyso approval for Protalix is the validation of the company’s plant-based manufacturing platform. The launch of Elelyso has set the stage for the development of additional biotherapeutics that are manufactured using this platform.