The Coming Lymphoma Vaccine: Will BiovaxID Deliver?

Biovest, the company behind the development of the coming therapeutic vaccine BiovaxID for the treatment of follicular non-Hodgkin's lymphoma, appears to be cruising through the regulatory approval processes in both Canada and the European Union, and no doubt that the US FDA is in their sights.

They have already secured orphan drug status for BiovaxID in the EU for both follicular lymphoma and mantle cell lymphoma. Discussions are ongoing with Canada's regulatory agency.

The man behind it all, Dr. Larry Kwak, who heads up the lymphoma department at MD Anderson Cancer Center, has been working on the development of this vaccine for more than two decades. Safe to say, success or fail it will be his legacy. One of the world's foremost experts in the field of lymphoma, he has staked his professional reputation on BiovaxID.

Cancer Vaccines

Unlike preventive vaccines, that inoculate a person against contracting a specific disease, cancer vaccines are therapeutic. Their intent is to treat an existing disease. While it would be nice to imagine receiving an inoculation against cancer, when set against what is known about the disease this is impractical to the point of being impossible.

Therefore, therapeutic cancer vaccines take the opposite approach and work from the disease outward, shaping themselves in the personalized image of the patient's own tumor, and calling for help from the body's immune system.

BiovaxID

The difference with BiovaxID is that it relies not on the tumor cell but on the cell surface proteins that are specific to that person's tumor—proteins that are important to the survival of the cell—and copies of them are made in the lab. It then combines the copies with an immune-enhancing agent (GM-CSF) as well as a foreign protein known as KLH, and the patient receives injections containing the cocktail. The foreign protein acts as a tripwire for the immune system, alerting it to respond to cells featuring these proteins and these proteins alone, and attack them, to the exclusion of other cells.

The Advantages of BiovaxID

Thus far, clinical trials have demonstrated a significant progression-free survival benefit from BiovaxID with a very low toxicity profile compared to immunotherapy such as Rituxan or chemotherapy such as the CHOP regimen. But BiovaxID offers a couple of extra potential benefits in both cost and administration.

Cost

While no one should expect BiovaxID to be inexpensive, neither should it earn the kind of devastating cost analysis that put shackles on Dendreon's Provenge therapeutic vaccine for prostate cancer. An estimate published in the New England Journal of Medicine around the time the vaccine hit the market set its estimated cost at $93,000. Accurate or not, this figure has stuck.

If we accept what we're told by Biovest's President and CEO, Samuel S. Duffey, then BiovaxID should be considerably more affordable, chiefly because its manufacture doesn't re-invent the manufacturing process; instead it takes advantage of processes already put in place by the manufacture of antibody products:

"To manufacture BiovaxID, we rely on well-controlled processes adapted from, and similar to, classic manufacturing of antibody products worldwide. Accordingly, our commercialization strategy requires only one centralized manufacturing facility to meet demand as opposed to multiple facilities. In addition, BiovaxID's shipping and handling resemble in most aspects the shipping and handling of currently marketed antibody drug products."

Administration

Rituxan maintenance therapy—as well as combination chemotherapy—requires a lengthy, tedious, and often trying infusion procedure that can run for hours on end. BiovaxID involves no infusions; rather it is administered as a series of subcutaneous injections.

Smooth Sailing? Not So Fast

Dendreon's Provenge can absolutely be credited with having paved the way for therapeutic cancer vaccines; before Provenge, the FDA had no regulations in place to direct their research and development. Not until October of 2011 did the FDA finally publish its guidelines regarding regulatory approval of this type of treatment.

Biovest therefore has been able to follow the path cut by Provenge even if the treatments are fundamentally different. However, they would be wise to remember that it wasn't smooth sailing for many of the early attempts at cancer vaccines, including Provenge: Despite receiving a unanimous 17-0 vote in 2007by the FDA’s Cellular, Tissue and Gene Therapies Advisory Committee in its favor, the agency did what it seldom does and it ignored the committee's recommendations and declined approval. Dendreon had to run another, larger Phase III trial, eating up three years and millions upon millions of dollars before finally receiving marketing approval.

Presumably, those over at Biovest know the history of cancer vaccines in the US and are working with the FDA to avoid making any of those mistakes.

Sources:
-Dimond, Patricia F, PhD. "How Provenge Laid the Groundwork for Developing and Regulating Cancer Vaccines." Genetic Engineering & Biotechnology News, 27 Feb 2012.
- Elvidge, Suzanne. "Overcoming Obstacles to Profitability," FierceBiotech Special Report.
- Kwak et al. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. NEJM. 1992 Oct 22;327(17):1209-15.