- Ultragenyx on Thursday said two patients with a rare liver enzyme disorder responded to treatment with its experimental gene therapy DTX301, while a third patient appeared to benefit. The three patients are in a trial to establish a therapeutic dose, and the company said it is planning to treat another three patients in this early-stage study.
- So far, six of the nine patients treated with the gene therapy have shown signs of response. The condition, called ornithine transcarbamylase deficiency, causes a dangerous buildup of ammonia in the blood.
- Shares in Ultragenyx surged by more than 30% to $58 apiece in morning trading Friday. Investors bid the price back up to levels last seen before the California-based company announced disappointing data for another gene therapy called DTX401.
Ultragenyx paid $151 million in 2017 to acquire Dimension Therapeutics for rights to DTX301 and DTX401, outbidding Regenxbio. Disclosure of early-stage data for both has therefore served as important milestones for investors trying to evaluate whether that transaction was worthwhile.
Where DTX401 fell short in a glycogen storage disorder, DTX301 has shown more signs of efficacy in ornithine transcarbamylase, or OTC, deficiency, a condition that limits the body's ability to metabolize protein.
The data Ultragenyx released Thursday afternoon were from a cohort of patients treated with 10 trillion genome copies of DTX301 per kilogram of body weight. The study is designed to measure if treatment leads to increases in the rates of ureagenesis, a sign of protein metabolism, and decreases of ammonia in the blood.
Two patients responded. One experienced an increase from a low of 24% of normal at baseline to 44% of normal one year after treatment, allowing for discontinuation of other drugs that help to remove nitrogen from the body and increased dietary consumption of protein.
A second patient had "uninterpetable" ureagenesis data due to high baseline values, but saw a 90% decrease in ammonia levels at week 24. Ultragenyx said this patients was on a tapering course of steroids to control immune response and had not changed other medications or diet.
A third patient was deemed a "potential" responder, having seen an increase in ureagenesis from 25% to 56% of normal at three months while still taking steroids, which have been shown to suppress ureagenesis, Ultragenyx said.
The company also said a patient in an earlier dosing group, which had been given 6 trillion genome copies per kilogram, was now counted as a responder, having observed her ureageneis rise from 20% of normal to 61% at one year and 64% at week 78. With this responder, there are now two from that dosing group.
Jefferies analyst Maury Raycroft called these results "better than expected" and potentially giving the biotech "a spark heading into 2020," he wrote in a Jan. 10 note to investors.
Ultragenyx said it is planning to enroll another dosing group of three patients in this trial at the 10 trillion genome copy level, but using steroids as part of the treatment regimen to limit immune response. SVB Leerink analyst Joseph Schwartz wrote that this could provide more consistent data, although it will stretch out the timeline for approval.
That lengthened timeline could make its December decision to sell off European royalty rights to Royalty Pharma for $320 million a wise one. The company had $123 million in cash along with $404 million in short term investments as of Sept. 30, 2019, but had spent $398 million over the first nine months of the year.
Meanwhile, the company is discussing Phase 3 trial design with the Food and Drug Administration. It said ammonia levels will likely be the primary endpoint based on FDA feedback, with ureagenesis used as a measure to support patient decisions to terminate alternative medications.