Michele Rayes used to take 64 pills a day to manage her hypoparathyroidism, a rare endocrine disorder that impairs calcium levels, dampens daily quality of life and can sometimes lead to chronic kidney disease.
Takeda’s Natpara wasn’t helping much. She continued experiencing a “3 o’clock crash” because of the drug’s short half-life and still relied on taking active vitamin D and what the patient community calls “rescue calcium.” After the Japanese drugmaker
recalled
Natpara due to manufacturing issues with rubber particulates, Rayes tried a new drug: Ascendis Pharma’s experimental daily injectable that replicates the natural parathyroid hormone in the body.
Natpara “was a toy; it was kids’ play,” said Rayes, who’s had the condition for three decades and is now an associate director at the HypoPARAthyroidism Association, which receives industry funding. “I never felt like I had my life back. I never felt that change in quality of life.”
This summer, the FDA approved the medicine, marketed as Yorvipath, and Rayes said she feels like she doesn’t “have a disease anymore,” saying she can now do daily activities that she hasn’t “done in decades.”
Yorvipath’s approval is one of multiple milestones this year for the hypoparathyroidism market.
“Clinical research has really intensified,” said Aliya Khan, a McMaster University endocrinologist who worked on Yorvipath’s late-stage trial and is the author of clinical
guidelines
.
Over the last year, Ascendis snagged FDA approval for Yorvipath. AstraZeneca bought a biotech with a late-stage candidate. MBX Biosciences
landed on the Nasdaq
in September to help finance a mid-stage injectable. And Septerna
went public in October
to raise money to support what it believes is the first oral candidate to enter human studies.
“You’re seeing the result of huge unmet need and a degree of innovation,” said Nicola Heffron, head of global marketing and market access at AstraZeneca’s Alexion.
The condition is thought to be one of the most common rare diseases, affecting about 100,000 people in the US and also in Europe. It’s “the last classical hormone deficiency for which there is no hormone replacement,” according to Aimee Shu, a VP of clinical development at Ascendis, and has been “stuck in a rudimentary situation” compared to other conditions like type 1 diabetes.
Multiple sources described the patient community as a vocal one. And the rise in R&D activity, coupled with growing awareness of the condition, could also lead to more diagnoses, said Patty Keating, the executive director of the HypoPARAthyroidism Association. She is also a patient who is participating in one of the blinded clinical trials.
Patients can inherit the condition or can acquire it by way of disruptions to their thyroid glands during surgery. It impacts multiple organs, including the brain, bones, kidneys and intestines.
Until recently, there have been few treatment options for patients aside from taking calcium and active vitamin D.
It’s a “completely different” landscape today compared to five years ago, according to Keating.
Since launching Yorvipath in Europe at the beginning of this year, Ascendis has seen a retention rate of about 99%, Ascendis CEO Jan Mikkelsen told
Endpoints News
.
Yorvipath had an “encouraging” launch in Germany and Austria, Jefferies analyst Kelly Shi told investors in early September. More details about the launch are expected in the company’s quarterly earnings on Thursday. Ascendis plans for the treatment to be in more than 10 European countries next year, plus the US, where it set a wholesale acquisition cost of $285,000 per year.
Rather than developing a prodrug like Ascendis, AstraZeneca is advancing a PTH receptor 1, or PTHR1, agonist that is also dosed daily. Dubbed eneboparatide, the investigational medicine aims to rid the need for calcium and vitamin D supplements while preserving bone mineral density, which is key for a patient population mainly comprising middle-aged women, according to AstraZeneca’s Heffron. The company got eneboparatide by way of its up to $1.05 billion acquisition of Amolyt Pharma in March.
“There’s definitely a need for treatments that deal with the root cause,” Heffron said. “This condition doesn’t go away, so they need something that’s going to be sustainable.”
AstraZeneca expects to have results from the
Phase 3 trial
in the first half of 2025, Heffron said. The small team at Amolyt was “quick off the blocks” in getting all the way to Phase 3, she said, and the UK drugmaker is now waiting with “bated breath” for the late-stage data.
Behind Ascendis and AstraZeneca are MBX, Septerna and an earlier-stage private startup called Confo Therapeutics, which declined to disclose details on its preclinical PTHR1 agonist.
MBX has a hormone replacement injectable, called
MBX 2109
, in
Phase 2
and expects to have topline results in the third quarter of 2025, MBX CEO Kent Hawryluk told Endpoints. The Indianapolis-area biotech went through a $163 million IPO in September to help advance the lead asset as well as a post-bariatric
hypoglycemia peptide, a preclinical obesity drug and other programs.
“We’re glad to see the progress in the space, the activity — most importantly for patients who really are in need of better treatments for hypoparathyroidism,” Hawryluk said.
The company hopes its once-weekly option will be a more accessible one for patients versus taking daily drugs. MBX aims to commercialize the drug on its own in the US, but it could seek partners for other regions, he said.
Septerna, meanwhile, entered a healthy volunteer study last month in Australia to test once- and twice-daily versions of its oral candidate called SEP-786. The startup has said it aims for Phase 1 data in mid-2025. After that, Septerna
has said
it will then test the PTH1R-targeting drug in Phase 2 in the US, Canada, Europe and other regions.
“We think that the game-changer for this whole space will be an oral small molecule,” CEO Jeffrey Finer told Endpoints at the time of Septerna’s
$150 million Series B
in 2023. “We’ve developed compounds that we believe should work as well as those injectable peptides.”
