High:
Low:
Wind:
Chance of precipitation:

Forecast

close
Sunday, August 25 Business

Loxo Oncology’s pioneering drug cures Bridgeport toddler’s cancer

Rihanna Plaza’s right arm is constantly moving.

It helps the lively 2-year-old from Bridgeport hug her baby brother, move to the beat in church, eat favorites like pizza and steak, help her father with DIY projects and even swipe some of her mother’s makeup.

Her arm might not have been able to do any of those things without a drug created by a company based 23 miles to the west.

The cancer that once threatened to disable the toddler’s right arm was cured during clinical testing of Vitrakvi, a drug developed by Stamford-based Loxo Oncology that was approved last November by the U.S. Food and Drug Administration. Designed to tackle the rare genetic mutation that caused Rihanna’s tumor and a number of other types, Vitrakvi represents a breakthrough treatment at a time of growing oncological care — and a financial boon for Loxo, which agreed last month to be bought for $8 billion.

“This will be part of Rihanna’s life forever,” Enrique Plaza, Rihanna’s father, said in sitting in the family’s home in Bridgeport’s East End. “Rihanna could be an example for other kids to get this medicine.”

A battle from birth

Rihanna was born Jan. 23, 2017, at St. Vincent’s Medical Center in Bridgeport.

Immediately after she was delivered, she was rushed into another room. Her parents saw the cause: An oozing, grapefruit-shaped tumor, the size of their newborn daughter’s head, enveloped her upper-right arm.

“I was in shock, I was surprised, I was confused — there was a lot going through my head at that time,” said Enrique, 36, a loader operator at green-waste specialist Harvest New England in Fairfield. “It was an open wound, and it was bleeding. It was shocking to see.”

The tumor was even more jarring because of the smooth pregnancy of Rihanna’s mother. Ana Plaza said she went for seven ultrasounds — including one done 10 days before Rihanna’s birth — at the Women’s Health Connecticut OB/GYN center in Bridgeport. None of those tests showed any complications, she said.

“The clinic had nice machines,” said Ana, 36, a loan officer for M&T Bank in Norwalk. “I though they should have caught it. How can they not tell you your daughter had this?”

A spokeswoman for Women’s Health Connecticut declined to comment, citing federal HIPAA privacy regulations.

Rihanna was transferred a couple of hours after her birth to the neonatal intensive care unit at Yale New Haven Hospital. There, she was diagnosed with a rare malignant tumor known as infantile fibrosarcoma. It forms in connective tissue, and it can occur anywhere in the body.

Shortly after her diagnosis, Rihanna started chemotherapy at Yale New Haven.

But after several months of treatment, she showed little progress. The chemotherapy dried up the tumor’s surface, so it no longer bled, but the mass had not shrunk much.

Read Full Article 

At that point, more chemotherapy would have been unlikely to work. Surgery to remove the tumor was not feasible, either. The cancerous growth was so deeply embedded that it could not be extricated without risking nerve damage that would have disabled Rihanna’s dominant arm.

But there was one more option. Yale New Haven doctors referred the Plazas to Memorial Sloan Kettering Cancer Center in Manhattan, where patient testing was underway for a promising cancer drug.

“We were desperate,” Ana said. “We would have gone anywhere.”

Innovative approach

Stamford-based Loxo was developing the new treatment, which is known generically as Larotrectinib.

Loxo, which takes its name from a Greek mythological reference to the trajectory of an arrow, started clinical trials for the therapy in 2014, a year after its founding.

Larotrectinib responds to the abnormal fusion of genes encoding for TRK proteins with other, unrelated genes. The drug inhibits the resulting, altered proteins that lead to tumor growth.

The TRK mutation catalyzed Rihanna’s tumor. It is also the source of many other types, including ones found in the lung, thyroid, breast, colon, skin and salivary gland.

“It doesn’t matter the site of origin of the tumor,” Loxo CEO Josh Bilenker said. “It doesn’t matter if it was a lung cancer or a thyroid cancer … (Larotrectinib) was instead developed around the DNA-specific abnormality.”

TRK-fusion cancers affect approximately 2,500 to 3,000 new patients in the U.S. each year. In comparison, about 1.74 million new U.S. cancer cases were estimated to have been diagnosed last year, according to the National Cancer Institute.

Dramatic results

The Plazas did not need much convincing to let Rihanna try Loxo’s medication.

“We were excited,” Enrique said. “Anything that would help Rihanna and save Rihanna, we were all for it. You would do anything for your child.”

In June 2017, she started on a twice-daily liquid formulation of Larotrectinib.

Within two days of the first dose, the tumor had drastically shrunk. Her right arm could go through a shirt sleeve for the first time.

“It’s pretty uncommon to find drugs that work so rapidly against tumors that prove to be so resistant to chemotherapy,” said Dr. Neerav Shukla, a pediatric oncologist at Memorial Sloan Kettering, who treated Rihanna.

Larotrectinib attacked the tumor without the infant suffering from side effects such as hair loss or lethargy. In contrast with chemotherapy, it only targeted cancerous cells.

By the time Rihanna underwent surgery at Memorial Sloan Kettering in early November 2017, the tumor had dwindled to smaller than the size of a golf ball.

“She may need some plastic surgery to taper the scar and make the contour of the shoulder look a little more appropriate,” said Dr. Todd Heaton, a pediatric surgical oncologist at Memorial Sloan Kettering, who operated on Rihanna. “But, as far as we can tell, the cancer is completely gone, and Rihanna should be done with any further surgery to remove it.”

In February 2018, she completed her final round of Larotrectinib.

Nine months later, the FDA approved the drug to be sold under the Vitrakvi brand name. It is Loxo’s first medication to go on the market.

The endorsement marked the FDA’s first for an oral medication to tackle the TRK fusion in advanced-stage solid tumors. It also represented the second time — after its 2017 greenlight for a Merck immunotherapy — that the agency had approved a cancer treatment based on a common bio-marker, rather than the part of the body where the tumor originated.

Loxo has developed and commercialized the drug with the support of pharmaceutical giant Bayer.

Vitrakvi’s “wholesale acquisition cost” is $32,800 for a 30-day supply of 100-milligram capsules, according to Bayer. A pediatric syrup, like the one Rihanna took, could cost $11,000 per month.

But, with the help of insurance and Bayer-funded subsidies, the majority of patients are expected to incur no more than $20 in monthly out-of-pocket costs, Bayer officials said.

Loxo has paid for all of Rihanna’s treatment at Memorial Sloan Kettering and also covered her family’s related travel expenses.

Growing demand

Vitrakvi, whose U.S. and European patents run until 2029, has hit the market at a time of surging demand for oncological treatment.

Global spending on cancer therapies and supportive-care drugs reached $133 billion in 2017, according to health care data firm Iqvia. During the next five years, the total is expected to rise to between $180 billion and $200 billion.

“When you have a drug like Vitrakvi, the bar is pretty high to beat it,” said Dr. Richard Frank, director of clinical cancer research for the Western Connecticut Health Network, which includes Norwalk, Danbury and New Milford hospitals. “For the foreseeable future, this will be the drug of choice for this mutation. But there are other important (genetic) targets that still have not been ‘drugable.’”

Reflecting the increasing value of its portfolio, Loxo last month agreed to an approximately $8 billion acquisition by Eli Lilly & Co., one of the country’s largest insulin makers. The terms put a 68 percent premium on Loxo’s stock.

More Loxo drugs are on the way. Its next treatment to hit the market could be Loxo-292, which targets the RET mutation in lung and thyroid cancers.

“A lot of biotech companies, even a lot of large pharma companies, think about the blockbuster, a mega product that sells a lot because there are a lot of patient customers for it,” Bilenker said. “We don’t think of it that way. We want to build very selective drugs for very specific purposes. It just means that we have to build more of them in succession.”

Meanwhile, Rihanna continues to thrive. She relishes being a big sister to 3-month-old brother Ricky and looks forward to serving as flower girl in her aunt’s wedding in July.

She still goes to Memorial Sloan Kettering for quarterly MRI checkups to ensure the cancer has not returned, but she has not required any additional medication.

A faint line of a surgery scar that runs along the underside of her upper-right arm is the only physical trace of her ordeal.

“She can do everything normally,” Ana said. “As long as she’s happy and healthy, that’s all we care about. That’s all that matters.”

pschott@scni.com; 203-964-2236; Twitter: @paulschott

Paul Schott|Staff reporter

loading