Some genetic diseases strike with extreme rarity but devastating effects. MPS VII afflicts only about 200 people worldwide in countries that report it, most of them children.

MPS VII (mucopolysaccharidosis type 7) causes skeletal abnormalities, typically short stature, along with heart-valve flaws, enlarged liver and spleen, and lung infections. In mild cases, an MPS VII patient can live to age 19 or 20 with delayed development and intellectual disability. A genetic flaw causes deficiency of an enzyme critical to breakdown of certain complex carbohydrates, which then accumulate and cause damage in tissues and organs.

Poppy, age 4, has MPS VII. She has a chance for a more normal life.

In November, the Food and Drug Administration approved an enzyme-replacement therapy called Mepsevii — the first ever — for Poppy and others who suffer from the condition. The infusions cost plenty, net revenue of $375,000 per patient per year for a child who weighs about 55 pounds. The cost is proportional to weight.

The treatment was developed by Novato-based Ultragenyx, which employs about 500. Poppy recently started taking Mepsevii. There is no data yet that shows improvement in lifespan on the enzymes.

Mepsevii marks a turning point not just for Poppy and others with ultra-rare MPS VII, but for Ultragenyx, a biotech company launched in 2010 that raised nearly $1 billion to fund its operations, including a stock sale in January that brought some $280 million. Mepsevii is the first product Ultragenyx is allowed to sell in the United States.

“We had a little bit of revenue from it in Europe,” said Emil Kakkis, founder, CEO and president of Ultragenyx. “Approval of Mepsevii is a pivotal moment for Ultragenyx,” he said, noting the “promise that the science … actually becomes something available for patients.”

For nearly eight years, Kakkis knew a patient in New York with MPS VII, according to Shalini Sharp, the company’s chief financial officer. “He was waiting for someone to pick this up and develop it,” she said. “By the time we were working on it, he was in respiratory failure. Our regulatory team was able to assist his physician in getting an emergency” investigational new drug application filing “so he could get treated before we started treating patients in clinical trials,” Sharp said. “He is still alive” and about age 16.

Scientists were pivotal in “letting this boy get treated,” she said, “and giving him more of a chance than he had. That’s the goal — to save their lives or improve their lives. It’s nice to come to work every day knowing that that’s what everybody is pulling for.”

In the U.S., there are roughly 40 people with MPS VII, Kakkis said. If an average patient weighs 55 pounds, Ultragenyx could derive $15 million in revenue in this country, and have a worldwide potential market of about $75 million.

“It’s not going to dramatically change things for us,” Kakkis said, in terms of revenue. “We have patients who were very sick and have gotten better,” he said. “It is definitely improving their quality of life. Each patient is very different in terms of their physical problems.”

Children with MPS VII who can walk may walk better on Mepsevii. Those “with terrible breathing problems breathe better,” Kakkis said.

Ultragenyx has made huge progress on treatments for two other diseases.

One is a rare genetic disease that results in low levels of phosphate in the blood. The malady — XLH — comes from a mutated gene linked to the X chromosome. The mutation causes hypophosphatemia. Children with XLH might have bowed legs and stand much shorter than other children the same age. As they reach teen years, they may develop pain in their bones, teeth and joints, and stop growing at under five feet.

Women have two X chromosomes; men have X and Y. A woman passes the disease to half her children, including daughters and sons. Men pass the disease to daughters but not sons. The gene can mutate in people with no family history of XLH. Roughly 50,000 people suffer from XLH in countries that track the disease.

Until now, treatment for XLH required that patients take high doses of vitamin D and phosphate — and painkillers. The treatment was marginally effective.

Ultragenyx experimented with an antibody called burosumab to treat XLH. On April 17, the Food and Drug Administration will decide whether to approve the drug for sale by Ultragenyx. A year’s treatment with burosumab will cost about $150,000, based on market analysts’ estimates.

Burosumab was developed by Tokyo-based Kyowa Hakko Kirin, which licensed the drug to Ultragenyx for sale in North America and other regions, not worldwide. The company will have access to about 12,000 XLH patients. If the FDA approves the treatment, Ultragenyx could see its first major stream of revenue in a year or two.

“We are commercializing it in partnership with Kirin in Japan,” Kakkis said. The partnership started in about 2013. “They continue to make the product. We haven’t finalized the price or presented it publicly” until the expected FDA approval in April.

Burosumab, a recombined fully human monoclonal antibody, also may be effective in another disease that damages bones called tumor-induced osteomalacia. The malady comes from a benign tumor somewhere in the body. “All of a sudden their bones start disintegrating,” he said. “It’s very debilitating.”

Burosumab helps both diseases by increasing the body’s absorption of phosphorus from the kidneys. In XLH and TIO, a hormone called fibroblast growth factor 23 reduces phosphorus and vitamin D in the blood. Burosumab binds to growth factor 23.

There are about 1,000 to 2,000 TIO patients in the Ultragenyx marketplace who might benefit from burosumab, Kakkis said, with a bigger range of dosage than for XLH. Many with TIO are wheelchair-bound due to the severity of bone damage.

Not all patients with the two diseases will use the new drug, if approved. “Pediatric patients will likely get on the drug with high frequency,” Kakkis said. “Not all adults may get treated — maybe half.”

At estimated total market of 13,000 and $150,000 a year, burosumab revenue through Ultragenyx could reach nearly $1 billion if half of patients use it. The revenue will be split in the licensing deal with KHK.

“We don’t know that it’s lethal,” Kakkis said of XLH, which resembles early onset osteoporosis. “They all were diagnosed when they were little. It’s severe. They have weak bones. They get fractures easily. They’re stiff, don’t move very well. They’re achy, with pains.” Many XLH patients end up with metal plates used to reinforce weak bones.

The disease creates risks such that “you probably are going to die younger,” Kakkis said. “No one has quantified that.”

Burosumab appears to dramatically improve healing from bone fractures, he said, by an estimated factor of 16. Its use may also “reduce pain and pain-medication use” over a period of six months to a year, he said. The medication must be prescribed by a physician and approved for treatment.

The product promises a potential market big enough that it could bring Ultragenyx to profitability within two or three years if all goes well, and burosumab annual revenue hits $500 million. SEC guidelines restrict the company from making predictions on revenue. The company had expenses of about $172 million for nine months last year, Sharp said, a burn rate of about $230 million a year.

The recent stock offering that brought more than $270 million “should take us to 2020 for sure,” Kakkis said, though not necessarily all the way to profitability.

“Demand was healthy” for the January offering, according to CFO Sharp. “The reason the market is excited about” burosumab, Sharp said, is that “it has near-term potential approval. The data has been really compelling in kids and adults. The market size is larger,” with North America, Latin America and part of Europe, she said, about 13,000 total patients.

“In 2010 it was me and my secretary,” Kakkis said. Significant financing came in June 2011 to launch the company. “It was a little bit scary. What we’re doing is meaningful. It’s not just about money. It’s a drive and justification for taking risks.”

Last year Ultragenyx acquired Boston-based Dimension Therapeutics for about $151 million. Dimension Therapeutics, founded in 2013, had about 50 employees who research gene therapy. “We have been working on integration of that company,” Sharp said. “They bring new drugs or therapies that we didn’t have before. It gives us the ability to use gene therapy, which we couldn’t have done before. They have strong capability in the manufacturing side.” Dimension Therapeutics was working on diseases with single-gene defects.

After the acquisition, the cash needs for Ultragenyx increased to about $280 million a year, Kakkis said.

Ultragenyx has several other drugs under development, including clinical trials. Early trials establish a drug’s safety and side effects. Later trials evaluate a drug’s effectiveness in comparison to existing treatments, if any. Positive results can lead a company to submit a new-drug application to the FDA seeking approval.

In August 2017, an Ultragenyx phase II clinical trial with extended-release aceneuramic acid — triheptanoin — failed in treating seizures associated with transporter type-1 deficiency syndrome. Glut1 DS, a rare metabolic disorder caused by a mutated gene, interferes with glucose transport in the brain and results in muscle wasting.

Ultragenyx still has triheptanoin scheduled in other 2018 trials to treat long-chain fatty-acid-oxidation disorders, where the body is unable to properly convert fat to energy. There are about 3,000 patients with the disorder in the U.S.

“In both situations, there’s a deficiency of energy metabolism,” Kakkis said. Ultragenyx has worldwide rights to triheptanoin, he said. The company would need separate approval in Europe and other parts of the world market.

With burosumab, Ultragenyx also filed for approval in Europe and Latin America. Regulators grant exclusivity for treatments of rare diseases in the U.S. and Europe, ranging from seven to 10 years. Patents on Mepsevii will extend market protection on that drug beyond the usual orphan-drug periods. “We have some innovation in the manufacturing process and composition of the product,” Sharp said. “This will be the first commercial product-sales revenue” for the company, she said, though Ultragenyx had modest revenue from collaboration agreements, for example. “It is exciting. There are many biotech companies that never launch a product” and never reach profitability.

Once the company markets one drug worldwide, subsequent products are easier to sell. “Every time you develop a drug, you can plug it into that infrastructure,” Sharp said. “You become more efficient.”

Taking a drug to market and achieving revenue for a biotech startup is a “huge change,” Kakkis said, “the important last mile of the development process.”

With the FDA’s expected ruling on burosumab just seven weeks away, there’s no guarantee, but based on clinical-trial results, “We feel confident that we will be launching the product in April,” Kakkis said. “We have product prepared. We have to get it packaged and labeled. We will be ready to go.”

Before launching Ultragenyx, Kakkis worked 11 years for BioMarin, which has nearby offices in Novato as well as in San Rafael. BioMarin also develops treatments for rare diseases in children. The mission to ease suffering in children can be compelling for scientists and others in biotech. “Once you’ve done it, you want to keep doing it again and again,” Kakkis said.

Such children often defy their myriad physical challenges and adopt an optimism about life. They “are remarkable people,” Kakkis said, “people we can learn from.”

James Dunn covers technology, biotech, law, the food industry, and banking and finance. Reach him at: james.dunn@busjrnl.com or 707-521-4257.