A Phase 1/2 Open-label, Multiple-dose, Dose-escalating Clinical Trial of the Safety and Tolerability of GTX-102 in Pediatric Patients With Angelman Syndrome (AS)
The primary objective of the study is to evaluate the safety and tolerability of multiple-ascending doses of GTX-102 administered by intrathecal (IT) injection to participants with Angelman Syndrome (AS).
Second quarter 2023 total revenue of $108.3 million, Crysvita® revenue of $83.0 million and Dojolvi® revenue of $16.5 million Total revenue grew 21% and total Crysvita revenue grew 20% versus the second quarter 2022 Reaffirmed 2023 expected total revenue guidance between $425 million to $450 million, Crysvita revenue of $325 million to $340 million, and Dojolvi revenue of $65 million to $75 million NOVATO, Calif., Aug. 03, 2023 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultrarare genetic diseases, today reported its financial results for the quarter ended June 30, 2023 and provided its financial guidance for the year. “In the second quarter, our global commercial efforts have resulted in continued meaningful growth of Crysvita, Dojolvi and Mepsevii revenue, including in our key territories outside of the U.S.,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “At the same time, we have continued to advance key clinical programs for osteogenesis imperfecta (OI), Angelman syndrome and Wilson disease, which are expected to generate a number of data catalysts over the next few quarters.” Second Quarter 2023 Selected Financial Data Tables and Financial Results Revenues (dollars in thousands), (unaudited)
Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Crysvita
Collaboration revenue in profit-share territory$19,799 $51,609 $69,705 $96,773 Royalty revenue 29,061 — 29,061 — Non-cash royalty revenue 17,270 5,423 22,152 10,261 Product sales 16,884 12,402 38,118 21,796 Total Crysvita revenue 83,014 69,434 159,036 128,830 Dojolvi 16,491 13,497 30,794 25,926 Mepsevii 8,439 4,933 16,919 9,794 Evkeeza 365 — 577 — Daiichi Sankyo — 1,479 1,479 4,728 Total revenues$108,309 $89,343 $208,805 $169,278 Total RevenuesUltragenyx reported $108.3 million in total revenue for the second quarter of 2023, which represents 21% growth compared to the second quarter 2022. This includes second quarter 2023 Crysvita revenue in North America of $61.3 million, which represents 19% growth versus the same time period in 2022. The growth in the region continued on its current trajectory while commercialization responsibilities for Crysvita in North America were transitioned from Ultragenyx to its collaboration partner Kyowa Kirin in April 2023. Selected Financial Data (dollars in thousands, except per share amounts), (unaudited)
Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Total revenues$108,309 $89,343 $208,805 $169,278 Operating expenses:
Cost of sales 9,914 8,270 22,171 14,370 Research and development 164,949 154,529 330,647 297,684 Selling, general and administrative 81,403 68,137 158,049 135,449 Total operating expense 256,266 230,936 510,867 447,503 Net loss$(159,828) $(158,162) $(323,800) $(310,482)Net loss per share, basic and diluted$(2.25) $(2.26) $(4.58) $(4.45) Operating Expenses Total operating expenses for the second quarter of 2023 were $256.3 million, including non-cash stock-based compensation of $34.7 million and a $9.0 million milestone expense upon initiation of the UX143 Phase 3 Orbit study. In 2023, annual operating expenses are expected to decrease as the company manages headcount and increases operational leverage while executing on high-value programs. Net Loss For the second quarter of 2023, Ultragenyx reported net loss of $159.8 million, or $2.25 per share basic and diluted, compared with a net loss for the second quarter of 2022 of $158.2 million, or $2.26 per share, basic and diluted. Cash, Cash Equivalents and Marketable Debt SecuritiesCash, cash equivalents, and marketable debt securities were approximately $618.4 million as of June 30, 2023. 2023 Financial Guidance For the full year 2023, the company expects: Total revenue in the range of $425 million to $450 millionCrysvita revenue in the range of $325 million to $340 million. This includes all regions where Ultragenyx will recognize revenue, including the royalties in Europe, which have been ongoing, and the royalties in North America, which began in April 2023.Dojolvi revenue in the range of $65 million to $75 millionNet Cash Used in Operations to be around $400 million Recent Updates and Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Two Phase 3 studies enrolling, additional Phase 2 data expected in mid-October Positive data from the dose-selection Phase 2 portion of the Phase 2/3 Orbit study were announced in June 2023 and showed that setrusumab rapidly induced bone production in patients with OI. Setrusumab treatment induced statistically significant increases in levels of serum P1NP, a sensitive marker of bone formation, and a substantial and significant improvement in bone mineral density (BMD) by three months. Serum P1NP levels through at least 1 month of treatment were available from all 24 patients enrolled in Orbit and demonstrated that treatment with setrusumab significantly increased serum P1NP, peaking at one to two weeks and again, as expected, after the 2-month dosing timepoint. The Phase 2 Orbit data demonstrated meaningful response in serum P1NP and BMD across both cohorts, with the majority of the effect observed at 20 mg/kg when compared to the 40 mg/kg cohort. The large increase in BMD observed in the Orbit patient population over the first 3 months was consistent with the rapid increase in serum P1NP levels and was similar to results that took 1 year to achieve in the ASTEROID study in adult OI patients. Treatment with setrusumab for 3 months resulted in an increase in lumbar spine BMD from baseline of 9.4% at 20 mg/kg (n=10), which represents a substantial mean change in Z-score of +0.65 from -2.12 (n=11) at baseline. Treatment with 40 mg/kg (n=7) resulted in a 9.8% BMD increase. Patients on placebo at the 3-month timepoint (n=2) showed no significant change in BMD or change in lumbar spine Z-score. As of the data cut-off, there had been no treatment-related serious adverse events observed in the study. Reported adverse events were generally consistent with those observed in the ASTEROID study and included infusion associated events, headache and sinusitis. There were no reported hypersensitivity reactions related to setrusumab. There were no safety-related differences observed between dosing groups or age groups. In July we announced, the first patients were dosed in both of the late-stage clinical trials, Orbit and Cosmic, which evaluate setrusumab in pediatric and young adult patients with OI. Orbit is expected to enroll approximately 195 patients at more than 40 sites across 12 countries. The Phase 3 Cosmic study is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <5 years. Cosmic is expected to enroll approximately 65 patients at more than 20 global sites. Additional data, including fracture frequency information, from the Phase 2 portion of the Orbit study are expected to be shared at an Analyst Day planned for mid-October. GTX-102 antisense oligonucleotide for Angelman syndrome: Phase 1/2 expansion cohorts enrolling; program update planned for mid-October 2023 In May 2023, the company announced that the FDA reviewed and agreed to a protocol amendment to the Phase 1/2 study of GTX-102 in pediatric patients with Angelman syndrome that enables the harmonization of dose ranges in the U.S. with those being used in ex-U.S. cohorts of the study. The Phase 1/2, open-label, dose-escalating study is evaluating the safety and tolerability of GTX-102 in pediatric patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The study is looking to verify the GTX-102 dose range and treatment regimen that will be used in the Phase 3 program. As of August 3, 2023, 19 patients have had more than 12 months of exposure to GTX-102, with the longest approaching two years. The dose escalation phase of this study was completed earlier in the year and dosing in the expansion cohorts is ongoing. As of the date of this release, patients from the dose escalation cohorts continue to exhibit encouraging dose and time-dependent clinical activity following longer-term treatment and maintenance dosing. No additional treatment-related serious adverse events or lower extremity weakness adverse events have occurred since the prior update in January 2023. Globally, sites are enrolling patients in the expansion cohorts and will evaluate the same safety, pharmacokinetic, and efficacy measures as the dose escalating cohorts. Enrollment has accelerated in the last two months as additional sites, including the U.S., have been activated and there are currently more than 20 patients enrolled at sites around the world. No lower extremity weakness safety events have been observed in patients in the expansion cohorts to date. An interim program update is expected at an Analyst Day in mid-October 2023. In the first half of 2024, the company expects to share data from the dose expansion cohorts on at least 20 patients who have been therapy for at least 6 months, which is expected to provide a meaningful comparison with natural history in this disease. UX701 AAV gene therapy for Wilson Disease: Stage 1 of pivotal clinical study dosing patients; expect Stage 1 enrollment completion around the end of the yearDosing in Stage 1 of the pivotal study is ongoing and is expected to enroll five patients per escalating dose cohort. In July 2023, the data safety monitoring board reviewed safety data from Cohort 1 and recommended escalating to the second dose level (1.0 x 10^13 GC/kg dose). Dosing in Cohort 2 has begun and Stage 1 is on track to complete enrollment around the end of the year. Interim Stage 1 data is expected in the first half of 2024 that would include safety and potentially initial signs of clinical activity. DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study completeIn May 2023, Ultragenyx announced the last patient had been dosed in the Phase 3 study. The 48-week study has fully enrolled patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 data are expected in the first half of 2024. DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patientsUltragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Analyst Day planned for mid-OctoberThe company intends to host an Analyst Day in mid-October to highlight additional Phase 2 Orbit clinical data, including fracture frequency information in patients with OI, and provide program updates on the pipeline, including GTX-102 for Angelman syndrome. Corporate updatesHoward Horn was appointed as Ultragenyx’s Chief Financial Officer (CFO) and Executive Vice President, Corporate Strategy, effective October 16, 2023. In this role, Howard will be responsible for leading the company’s finance, accounting, corporate strategy, and investor relations functions. He will report to Emil D. Kakkis and will serve on the Executive Leadership Team. Conference Call and Webcast Information Ultragenyx will host a conference call today, Thursday, August 3, 2023, at 2 p.m. PT/5 p.m. ET to discuss the second quarter 2023 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI0d56bd62c7cc44be8c2fe4ce58f2318c), and you will be provided with dial in details. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease. The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency. For more information on Ultragenyx, please visit the company's website at: www.ultragenyx.com. Forward-Looking Statements and Use of Digital Media Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, risks related to serious or undesirable side effects of our product candidates, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, our limited experience in generating revenue from product sales, risks related to product liability lawsuits, our dependence on Kyowa Kirin for the commercial supply of Crysvita, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs, delays, difficulties or adverse impact to revenue related to such transition, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 5, 2023, and its subsequent periodic reports filed with the SEC. In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/).
Ultragenyx Pharmaceutical Inc.Selected Statement of Operations Financial Data(in thousands, except share and per share amounts)(unaudited)
Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Statement of Operations Data:
Collaboration and license$19,799 $53,088 $71,184 $101,501 Product sales 42,179 30,832 86,408 57,516 Royalty revenue 46,331 5,423 51,213 10,261 Total revenues 108,309 89,343 208,805 169,278 Operating expenses:
Cost of sales 9,914 8,270 22,171 14,370 Research and development 164,949 154,529 330,647 297,684 Selling, general and administrative 81,403 68,137 158,049 135,449 Total operating expenses 256,266 230,936 510,867 447,503 Loss from operations (147,957) (141,593) (302,062) (278,225)Change in fair value of equity investments 261 (10,184) (73) (19,513)Non-cash interest expense on liabilities for sales of future royalties (15,375) (6,052) (31,011) (12,636)Other income (expense), net 3,975 (31) 10,573 752 Loss before income taxes (159,096) (157,860) (322,573) (309,622)Provision for income taxes (732) (302) (1,227) (860)Net loss$(159,828) $(158,162) $(323,800) $(310,482)Net loss per share, basic and diluted$(2.25) $(2.26) $(4.58) $(4.45)Weighted-average shares used in computing net loss per share, basic and diluted 70,897,991 69,925,358 70,639,015 69,722,141
Ultragenyx Pharmaceutical Inc.Selected Activity included in Operating Expenses(in thousands)(unaudited) Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022
Non-cash stock-based compensation$34,653 $35,865 $66,592 $65,252 UX143 clinical milestone$9,000 — $9,000 —
Ultragenyx Pharmaceutical Inc.Selected Balance Sheet Financial Data(in thousands)(unaudited) June 30, December 31, 2023 2022 Balance Sheet Data: Cash, cash equivalents, and marketable debt securities$618,352 $896,732 Working capital 457,758 622,689 Total assets 1,311,310 1,545,444 Total stockholders' equity 129,030 352,494
Contacts Ultragenyx Pharmaceutical Inc.InvestorsJoshua Higair@ultragenyx.com MediaJeff Blakemedia@ultragenyx.com
LAVAL, Québec, June 23, 2023 /PRNewswire/ -- Acasti Pharma Inc. ("Acasti" or the "Company") (Nasdaq: ACST), a late-stage, biopharma company advancing GTX-104, its novel formulation of nimodipine that addresses the high unmet medical needs for a rare disease, aneurysmal subarachnoid hemorrhage (aSAH), today announced financial and operational results for the fiscal year ended March 31, 2023.
United States Food and Drug Administration (FDA) has confirmed the 505(b)(2) regulatory pathway for GTX-104 and that the GTX-104-002 PK study may have met the criteria for a scientific bridge.
Successfully submitted GTX-104 Pivotal Phase 3 Safety Study protocol Investigational New Drug (IND) amendment to the FDA with the expectation that a first patient will be dosed in the second half of calendar 2023.
Implemented strategic transformation of operating model to an agile biopharma reflecting its operational focus on GTX-104. In alignment with the new operating model, Acasti has brought on a small and highly experienced new management team with deep subject matter knowledge and direct, hands-on clinical trial experience in aSAH.
Significant extension of the Company's cash runway which is expected to be sufficient to fund the Company through calendar Q2 2025 and the achievement of critical value inflection milestones, including a potential New Drug Application (NDA) filing for GTX-104.
Evaluation of strategic alternatives to maximize value of de-prioritized pipeline assets (GTX-102 and GTX-101).
The Company finished the fiscal year ended March 31, 2023, with $27.9 million in cash, cash equivalents and short-term investments.
Prashant Kohli, Chief Executive Officer of Acasti, said, "After receiving positive clarifying feedback from the FDA on the proposed Phase 3 Safety Study for GTX-104 whereby they concurred with the suitability of the 505(b)(2) regulatory pathway and that Acasti's GTX-104-002 PK study may have met the criteria for a scientific bridge, we moved swiftly to submit the full protocol for our pivotal Phase 3 Safety Study in May 2023. Further, we implemented a strategic realignment plan to maximize shareholder value, including a strategic transformation of Acasti's operating model to that of an agile biopharma company which we believe allows our cash runway to be sufficient to achieve a potential NDA filing for GTX-104 in 2025. Our new, highly motivated, and energized organization is entirely focused on achieving critical value inflection milestones in the quarters and years to come."
FY 2023 Financial Results
The Company's consolidated financial statements have been prepared in accordance with generally accepted accounting principles in the United States of America and are presented in U.S. dollars.
Research and development expenses, net of government assistance for the twelve months ended March 31, 2023, totaled $9.9 million compared to $5.6 million for the twelve months ended March 31, 2022. Our research and development during the year ended March 31, 2023 was focused primarily on three clinical development programs GTX-104, GTX-102, and GTX-101 drug candidates. Due to the strategic realignment announced on April 4, 2023, the Company will focus its future research and development expenses exclusively on GTX-104. Future development of GTX-102 and GTX-101 will depend on additional dedicated funding or the signing of a strategic partnership. Research and development expenses during the year ended March 31, 2022, related to the completion of our TRILOGY Phase 3 clinical program for our former drug candidate CaPre, as well as the initiation and progression of development work related to GTX-104, GTX-102 and GTX-101.
General and administrative expenses for the twelve months ended March 31, 2023 were $7.6 million compared to $9.3 million for the twelve months ended March 31, 2022. The decrease was primarily a result of decreased legal, tax, accounting and other professional fees related to the Grace merger for the year ended March 31, 2022. Due to the strategic realignment announced on April 4, 2023, the Company is over time discontinuing its operations in Canada and has proceeded to lay off substantially all its workforce, allowing Acasti's new management team to rebuild a leaner organization in the United States.
As a result of the strategic realignment plan announced on April 4, 2023 to prioritize resources to GTX-104, and away from GTX-101 and GTX-102, the company incurred an impairment of intangible assets of $28.7 million, and an impairment of goodwill of $4.8 million, for the period ended March 31, 2023.
Loss from operating activities for the twelve months ended March 31, 2023 was $52.1 million compared to a loss of $15.6 million for the twelve months ended March 31, 2022. The change is primarily a result of the combined $33.5 million impairments to intangible assets and goodwill mentioned.
For the twelve months ended March 31, 2022, a financial gain of $5.1 million resulted mostly due to the decrease in the fair value of the derivative warrant liabilities.
Net loss and total comprehensive loss for the twelve months ended March 31, 2023 was $(42.4) million, or $(0.95) loss per share, compared to a net loss of $(9.8) million, or $(0.27) income per share, for the twelve months ended March 31, 2022. The change is primarily a result of the combined $33.5 million impairments to intangible assets and goodwill mentioned.
Cash, cash equivalents and short-term investments totaled $27.9 million as of March 31, 2023, compared to $43.7 million in cash, cash equivalents and short-term investments as of March 31, 2022. Based on management's current projections, current cash, cash equivalents and short-term investments are expected to be sufficient to fund the Company through calendar Q2 2025, facilitating achievement of critical value inflection milestones, including a potential New Drug Application (NDA) filing for GTX-104.
Acasti is a late-stage biopharma company with drug candidates addressing rare and orphan diseases. Acasti's novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery. Acasti's lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provides seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Acasti's lead clinical asset, GTX-104, is an intravenous infusion targeting aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull.
For more information, please visit: .
Statements in this press release that are not statements of historical or current fact constitute "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking statements"). Such forward looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Acasti to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, readers are urged to consider statements containing the terms "believes," "belief," "expects," "intends," "anticipates," "estimates", "potential," "should," "may," "will," "plans," "continue", "targeted" or other similar expressions to be uncertain and forward-looking. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. The forward-looking statements in this press release, including on the Company's anticipated cash runway, are based upon Acasti's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions of the planned Phase 3 safety study for GTX-104; (ii) regulatory requirements or developments and the outcome and timing of the proposed IND application for GTX-104; (iii) changes to clinical trial designs and regulatory pathways; (iv) legislative, regulatory, political and economic developments; (v) actual costs associated with Acasti's clinical trials as compared to management's current expectations; and (vi) the projected extension of the Company's cash runway to calendar Q2 2025. The foregoing list of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and are filed by Acasti from time to time with the Securities and Exchange Commission and Canadian securities regulators. All forward-looking statements contained in this press release speak only as of the date on which they were made. Acasti undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by applicable securities laws. The NASDAQ does not accept responsibility for the adequacy or accuracy of this release.
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SOURCE Acasti Pharma Inc.
Evercore ISI analysts said Roche’s decision is good overall for Ultragenyx.
Roche has bowed out of the race to develop an antisense oligonucleotide (ASO) for Angelman syndrome. After getting a look at early efficacy data, the Swiss drugmaker opted against advancing the candidate, switching its Angelman focus to another asset and leaving the ASO space to Biogen, Ionis Pharmaceuticals and Ultragenyx.
Basel-based Roche was one of a small band of drug developers to hit on the idea of using ASOs to boost expression of UBE3A, the neuronal E3 ligase that is at the root of the severe neurodevelopmental disorder. A phase 1 clinical trial of Roche’s ASO, rugonersen, began in 2020, but that is as far as the drug candidate will get under the Swiss drugmaker.
“Roche has taken the decision not to progress rugonersen into the next stage of clinical development,” a spokesperson said. “The molecule was well tolerated and had an acceptable safety profile. Roche is committed to finding the best possible solution for rugonersen and people living with Angelman syndrome.”
News of Roche’s decision emerged via the patient community, with FAST, an Angelman advocacy group, putting out a blog post after learning of the revised development plan for rugonersen. In the post, FAST said Roche saw “encouraging effects” from electroencephalogram testing but the changes fell short of its criteria for taking the asset forward. Roche will continue an open-label extension study and is looking to partner the molecule.
After hearing the news, analysts at Evercore ISI spoke to Ultragenyx and, in a note to investors, said “they always thought Roche’s ASO didn't have enough potency and in our recent meeting with them wondered about [the] future of the molecule.” Patients are already contacting Ultragenyx about switching to a trial of its ASO, according to the analysts, and transferring “should be okay with the right washout period.”
Ultragenyx’s GTX-102 is one of two UBE3A ASO options open to Angelman patients who want to switch from Roche’s rugonersen to a similar molecule. BIIB121, an Ionis candidate that Biogen has the option to license, is the other ASO. The candidates are in phase 1 trials that are scheduled to wrap up in 2025, years later than originally planned for both GTX-102 and BIIB121, also known as ION582.
Overall, the Evercore ISI analysts said Roche’s decision is good for Ultragenyx because it means less competition, but they acknowledged it is impossible to rule out that the efficacy limitations of rugonersen are a classwide problem that will affect GTX-102 and BIIB121. Ultragenyx and GeneTx, its partner on GTX-102, shared some data on their ASO last year, but the release left many questions unanswered.
At Roche, Angelman attention now turns to alogabat, a GABA modulator that moved into phase 2 late last year. Roche, which currently lists one recruiting location, is activating sites, according to FAST.