Biologic drugs have profoundly transformed modern medicine. Targeting molecular processes that few conventional drugs can, biologics offer patients not only first-of-kind treatments, but in some cases, cures.
While oncology drugs dominate the list, new biologics have dramatically changed the treatment paradigm for diseases such as rheumatoid arthritis, diabetes, lupus and multiple sclerosis. Sophisticated and cutting-edge biologic treatments consistently steal the headlines and speculation about future capabilities is seemingly limitless. But there is another aspect of biologics that makes them stand out: Price and availability.
The complex processes needed to develop and bring drugs harvested from living cells to market often translates into exorbitant prices.
Currently, Novartis’ Zolgensma — a one-time gene therapy treatment for spinal muscular atrophy — is the world’s most expensive drug, boasting a whopping $2.1 million price tag.
Yet accessibility issues are not limited to the extravagantly expensive biologics. It has been estimated that on average, a daily dose of a biologic costs 22 times more than that of a small molecule drug.
Biologic cost constraints compound what is already a serious accessibility issue. According to the World Health Organization (WHO), nearly 2 billion people have no access to basic medicines. Drug accessibility is an ongoing, multifarious obstacle around the world. It’s a problem that for years has been vexing governments, global health agencies and also, Barry Holtz.
Holtz, who is considered one of the pioneers of plant-made biotherapeutics, has enjoyed a decorated 40+ year career in biopharma, founding several successful companies along the way. And while Holtz jokes that he briefly contemplated retirement and “playing guitar badly for the rest of my days,” ultimately, he was not quite ready to put his plants out to pasture.
“A group of us realized that biologics manufacturing in the world is still lacking. It’s still not well served in all areas, and it certainly is not served for populations that have special or unique needs,” says Holtz.
So Holtz, together with a close-knit group of experts that have previously teamed on multiple award-winning projects, hatched a plan to help get medicines to underserved areas of the world.
Phylloceuticals is born
On Feb. 3, Holtz became the CSO of a new global technology company, the backbone of which depends on a well-developed and proven platform of plant-made pharmaceuticals (PMP). The company is aptly named Phylloceuticals — “phyllo” is a Greek word meaning “leaf.”
On the surface, Phylloceuticals’ mission is as straightforward as the technology the company will utilize to achieve it. The company will use plant-made pharmaceuticals to enable regions and countries to quickly ramp up production of much-needed biologics.
“Its simplicity is really the driver. We grow a generic plant bioreactor. Plants have all the cellular machinery found in mammalian cells. Once mature, we inoculate the plants with a vector that introduces a new gene. The plant manufactures the protein for five to seven days, and then we harvest the plant and extract the protein,” says Holtz.
But PMPs alone are not a novelty. There are several established biotech companies using PMPs to speed production and lessen capital expenses. The concept is growing more prolific and is recognized by regulators around the world.
Instead, it’s Phylloceuticals’ business model that sets it apart. Neither a CDMO nor a drug company, Phylloceuticals will employ a proprietary platform known as PhAAST — Pharmaceuticals as a Service Technology. This essentially boils down to working with private and public entities to do everything it takes to get facilities up and running in underserved regions.
“We’re there to help from the very beginning — from selecting what product to produce, to designing and building facilities, even helping find staff to run them. Our intent is to do everything to support these facilities throughout the lifecycle,” says Holtz’ partner and friend, Bill Brydges.
Brydges has taken the reigns as Phylloceuticals’ CEO. Like Holtz, Brydges is a familiar face in biopharma. Having started his career as a chemical engineer, Brydges was a founding leader of Biokinetics, which became a renowned biopharma project engineering firm.
Phylloceuticals will provide clients with a proven production system and ongoing support, which will ultimately empower safe, stable and affordable local biologic production.
“As time goes on, they’ll build that infrastructure themselves, and be able to become independent. That’s our goal,” says Brydges.
The rituximab example
While the PMP platform is applicable to many different drugs, Phylloceuticals plans to initially focus on monoclonal antibodies (mAbs). One in particular the company has set its sights on is rituximab.
When rituximab was approved by the U.S. Food and Drug Administration in 1997 (under the brand name Rituxan), the mAb revolutionized the treatment of certain forms of non-Hodgkin’s lymphoma. Today, rituximab, in conjunction with what’s known as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy has become an accepted standard of care for numerous lymphoma cancers — many of which are curable with relatively short courses of therapy but lethal if left untreated. Rituximab is also increasingly being prescribed for the treatment of autoimmune diseases such as rheumatoid arthritis.
“We take it for granted here in the U.S. that if you have non-Hodgkin’s lymphoma, you’re going to get rituximab. It’s off the shelf,” says Holtz. “Well that’s not the case in South Africa, where pregnant women suffering from AIDS get non-Hodgkin’s lymphoma and then don’t even have access to rituximab.”
Several global efforts have facilitated better access to the treatment. In 2017, the FDA approved a rituximab hyaluronidase combination that could be administered by subcutaneous injection rather than infusion, cutting the treatment time down to minutes and eliminating the need for infusion pumps. This dramatically reduced delivery times as well as the need for clinical staff trained in drug infusion, further facilitating rituximab application in low-resource settings.
Over the past few years, several less expensive biosimilar versions of the reference drug have been approved by global regulatory agencies. While the average cost of treatment with Roche’s Rituxan can range in the tens of thousands of dollars per year in the U.S., in some cases, pricing for rituximab biosimilars is less than half of that. In 2018, the WHO launched a biosimilar prequalification pilot program specifically targeting rituximab in order to smooth the path to greater adoption in nations with fewer resources. Drugmakers could submit drugs to the program and drugs that met GxP requirements were placed on WHO’s list of prequalified medicines. This list was then used by United Nations agencies and member states when selecting medicines to purchase and distribute throughout low- and middle-income countries.
And yet, even with these types of efforts, decades after approval, many mAbs like rituximab still remain unavailable to patients, especially in developing countries.
For Phylloceuticals, mAbs are just the entry point for biologics manufacturing in underserved regions.
“We know that mAbs, like rituximab, are key in the fight against cancer — one of the fastest growing disease states in underserved areas. Phylloceuticals will link the knowledge base from these areas to continuously improve the technology, and add new and appropriate products to the roster. We will be supporting our customers for the long haul,” says Brydges.
While increasing the supply of one essential drug could save countless lives, it’s not enough to put a dent in a behemoth problem like drug accessibility.
“Creating one product and trying to distribute it around the world won’t fill the specialized needs out there,” says Brydges.
Ultimately, Phylloceuticals looks to empower vulnerable regions with the infrastructure and technology necessary to boost local production and continuously serve the treatment needs of their own local populations.
And while no one is denying that the company’s compelling value proposition is such that it should reap fairly large financial rewards, Holtz still wants Phylloceuticals to change the world.
“It might sound a little schmaltzy, but Bill and I, and our partners, have all enjoyed really good careers, and I think we’ve all been productive and done good things,” Holtz says. “But my motto is, ‘There’s always time to do good and time should be well spent for that.’ I’m looking forward to this because I think it’s a good thing.”
Want to here more? Listen to our podcast on "Growing the biologic drug supply."