Keeping Track: Idorsia’s Quviviq Is FDA’s First Novel Approval Of 2022; AbbVie’s Rinvoq Gains Eczema Claim

The latest drug development news and highlights from the Pink Sheet’s US FDA Performance Tracker

January started off quiet in terms of US FDA approval actions, but Idorsia Ltd.’s insomnia drug Quviviq took the title of the first novel agent to clear the agency in 2022.

The beleaguered Janus kinase (JAK) inhibitor continues to move past the safety concerns that caused a rash of missed user fee goal dates last year. AbbVie Inc.’s Rinvoq received an indication for atopic dermatitis, or eczema – a potentially massive commercial opportunity – and submitted a new supplemental new drug application in axial spondyloarthritis.

Viatris and Biocon revealed a complete response letter for a biosimilar version of rapid-acting insulin aspart.

And in submissions, AstraZeneca PLC is seeking a myasthenia gravis indication for its second complement inhibitor, Ultomiris, and Mitsubishi Tanabe Pharma Corporation submitted an application for an oral formulation of its amyotrophic lateral sclerosis therapy edaravone, which is approved for IV use as Radicava.

Idorsia’s Quviviq Wants To Wake Up Orexin Antagonist Space

Idorsia’s Quviviq (daridorexant) is the third orexin receptor antagonist to receive FDA approval for insomnia, but the Swiss company thinks the drug will stand out from Merck & Co., Inc.’s Belsomra (suvorexant) and Eisai Co., Ltd.’s Dayvigo (lamborexant) based on the labeling approved on 7 January for treatment of adults with insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

While the primary endpoints of the Quviviq pivotal trials evaluated sleep onset and sleep maintenance, using polysomnography to measure Latency to Persistent Sleep (LPS) and Wake After Sleep Onset (WASO), the company’s messaging will highlight how awake patients might feel the next morning. Idorsia noted that daridorexant has a “rapid absorption for sleep onset, and a pharmacokinetic profile such that around 80% of daridorexant has been eliminated after a night of sleep to help minimize residual effects.”

An unbranded ad campaign, called Seize The Night And Day and starring actress Jennifer Aniston, will emphasize that “when you have a bad night, you have a bad day,” Idorsia CEO Jean-Paul Clozel told the J.P. Morgan conference. (Also see "Idorsia Adds Hollywood Sparkle To Sleep Drug Quviviq" - Scrip, 12 Jan, 2022.)

The pivotal trials of Quviviq included a key secondary endpoint evaluating daytime sleepiness using the sleepiness domain score from the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). The 50mg dose, tested in one Phase III trial, showed significant reduction in daytime sleepiness at months 1 and 3 compared with placebo, the company reported. However, “results on this endpoint for the 25mg dose did not reach statistical significance in either study at both timepoints.”

“What is truly impressive, we have shown a dose response in the efficacy of daridorexant, with no increase in the rate of somnolence or fatigue with increasing doses,” Idorsia head of global clinical development Guy Braunstein declared in a press release. As an adverse reaction, somnolence or fatigue was reported by 6% of 25mg patients and 5% of 50mg patients, as well as 4% of placebo patients.

Quviviq, like its fellow orexin antagonists Belsomra and Dayvigo, carries a label warning about impaired daytime wakefulness, “even when used as prescribed.” Belsomra’s warning is the most extensive, noting that “impairment can occur in the absence of symptoms, and may not be reliably detected by ordinary clinical exam” and more strongly warning about driving ability the day after use.

Quviviq was studied in two placebo-controlled Phase III trials that administered the drug once daily for three months. In the first study, 930 patients were randomized to 50mg or 25mg daridorexant or placebo. In the second study, 924 patients were randomized to daridorexant 25mg, 10mg, or placebo. Only the 50mg and 25mg doses were approved by the FDA; the 10mg dose did not show improvement over placebo.

Quviviq’s launch is expected in May 2022, after the US Drug Enforcement Administration completes controlled substances scheduling.

AbbVie’s Rinvoq Ramps Up As JAK Concerns Recede

Six months after the extended user fee goal date for AbbVie’s JAK inhibitor Rinvoq (upadacitinib) in atopic dermatitis, the company announced FDA approval on 14 January 2022.

The logjam of JAK inhibitor applications that occurred while the FDA addressed safety concerns started to break up after the agency’s 1 September 2021 decision to update box warnings and urge that JAK inhibitors be reserved for patients who do not respond to or cannot tolerate TNF blockers.

An sNDA for Rinvoq in psoriatic arthritis cleared on 14 December 2021 was the first of AbbVie’s applications pending past their user fee goals to receive approval. The atopic dermatitis indication, however, could be the most commercially significant. It is also the only Rinvoq claim to have received a breakthrough therapy designation.

Rinvoq is indicated for treatment of moderate to severe atopic dermatitis in adults and children 12 years of age and older whose disease did not respond to previous treatment or is not well controlled with other medicines including biologics, or when other therapies are not recommended.

The new claim is supported by three placebo-controlled Phase III trials that enrolled a total of more than 2,500 patients. The Measure Up 1 and 2 trials tested Rinvoq monotherapy, while the AD Up study combined Rinvoq with topical corticosteroids. All of the trials met the primary endpoints, which measured skin clearance at 16 weeks.

AbbVie highlighted Rinvoq’s effect on a secondary endpoint measuring pruritis, or itching, reporting that “in all three studies, a significant improvement in itch (Worst Pruritus NRS ≥4) was observed as early as week one, compared to placebo.”

AbbVie noted that Rinvoq was approved in two once-daily oral dose strengths, 15mg and 30mg, for AD. The 15mg dose is recommended as the initial dose for adult and pediatric patients weighing at least 40kg. Children and adults younger than 65 years who do not respond adequately can increase the dose to 30mg.

On 7 January, AbbVie announced the submission of an application for Rinvoq 15mg to treat adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation who have responded inadequately to NSAIDs.

A supplemental NDA for Rinvoq the other subset of ankylosing spondyloarthritis, ankylosing spondylitis, is still pending after a likely June 2021 user fee goal date.

AbbVie’s 7 January statement reported that it has provided data to the FDA from the Phase III SELECT-AXIS 2 in AS patients with inadequate response to biologic disease-modifying anti-rheumatic drugs as well as two-year results of the Phase II/III SELECT-AXIS 1 trial. The new data are intended “in support of the agency’s ongoing review” of the sNDA for adults with active AS.

Viatris/Biocon Announce CRL After Receiving FDA-483

Viatris Inc. and Biocon, Ltd. will need to wait on a fast-acting insulin analog counterpart to their long-acting Semglee (insulin glargine-yfgn) biosimilar after the FDA issued a complete response letter for their insulin aspart biosimilar, announced on 7 January 2022.

Semglee, a biosimilar version of Sanofi’s Lantus, won the first interchangeable biosimilar designation from the FDA in July 2021. (Also see "US Biosimilar Approvals In 2021 Were Few But Included Many Firsts" - Pink Sheet, 4 Jan, 2022.)

The companies are seeking an interchangeable biosimilar designation for the insulin aspart candidate as well. Interchangeability would allow pharmacy-level substitution of Viatris/Biocon’s insulin aspart with the reference product, Novo Nordisk A/S’s rapid-acting NovoLog.

While the companies did not disclose the issues raised by the CRL, Biocon’s Malaysian manufacturing facility received a Form 483 with a total of six observations of GMP deficiencies after a pre-approval inspection for the biosimilar insulin aspart in September 2021. (Also see "Biocon And Viatris Get CRL From FDA On Insulin Aspart" - Generics Bulletin, 10 Jan, 2022.)

“The CRL did not identify any outstanding scientific issues with the product,” Biocon said.

AZ Uses PRV To Grow Myasthenia Gravis Franchise

AstraZeneca’s rare disease business Alexion Pharmaceuticals Inc. used a rare pediatric disease priority review voucher (PRV) to shorten the review timetable for the long-acting C5 complement inhibitor Ultomiris (ravulizumab-cwyz) in a new indication: treatment of generalized myasthenia gravis (gMG).

Ultomiris has a priority review user fee goal date for gMG in the second quarter, likely in April.

Alexion is already familiar with the gMG market. Alexion’s older complement inhibitor Soliris (eculizumab) received an indication for refractory gMG in anti-acetylcholine receptor (AChR) antibody-positive patients in October 2017.

Ultomiris “may help a broader range of patients including those with milder symptoms or who are earlier in their treatment journey,” the company said. The pivotal Phase III trial had “no requirement for prior treatment failure, and patients could stay on stable standard of care medicines.”

The global study, which enrolled 175 patients with anti-AChR antibodies, assessed change from baseline in a patient-reported activities of daily living scale at week 26. A two-year open-label extension is ongoing; the sBLA includes preliminary data from 75 patients who had a total of 52 weeks of treatment.

When Soliris was approved for gMG almost four and half years ago, it was the first new treatment for the rare autoimmune disorder in “approximately 60 years,” Alexion noted. The gMG space has recently grown hotter, with the 17 December 2021 approval of argenx N.V.’s novel agent Vyvgart (efgartigimod alfa-fcab).

Nonetheless, both Soliris and Vyvgart received standard reviews – something AstraZeneca was determined to avoid this time around.

Mitsubishi Tanabe Bids To Take Radicava Oral

Mitsubishi Tanabe is also working to expand its presence in an underserved rare disease, amyotrophic lateral sclerosis (ALS). The company’s Radicava (edaravone) was approved in May 2017 for IV treatment of ALS. Now, the company is seeking approval of an oral suspension formulation.

The FDA granted priority review to oral edaravone, known as MT-1186, with a 12 May 2022 user fee goal date.

Oral edaravone was developed to have a “similar clinical profile” to the approved IV formulation.

The new NDA is supported by a 24-week Phase III trial in ALS patients, data from the Radicava IV pivotal trial, and “upwards of seven Phase I clinical pharmacology studies examining the pharmacokinetics, safety, drug-drug interactions, dosing, bioavailability and bioequivalence of the oral suspension in healthy individuals and ALS patients with and without PEG/NGT,” the company said.