26 Feb 2021
While its NDA languishes at the US Food and Drug Administration, the EMA’s CHMP has said yes to dostarlimab’s marketing...
The ACR/ARHP Annual Meeting in San Diego offered new details from studies of new and existing therapies across a range of rheumatic diseases, from rheumatoid arthritis to rare diseases. Scripshares notes here from interviews with Lilly, Ironwood, Corbus and Samumed.
The American College of Rheumatology (ACR)/Association of Rheumatology Health Practitioners (ARHP) Annual Meeting taking place in San Diego from Nov. 4 to 8 yielded updates on a range of biopharmaceutical products, from assets in the research and development pipeline to drugs on the market for several years.
Scrip attended the meeting on Nov. 6 and 7. More highlights from the meeting and interviews with biopharmaceutical executives will be reported in the days to come.
Eli Lilly & Co. presented new data at the ACR/ARHP meeting that it hopes will add a point of differentiation for baricitinib if approved for rheumatoid arthritis next year. The oral therapy developed in partnership with Incyte Corp. showed that RA patients had greater and earlier pain reduction than those who were treated with AbbVie Inc.'s blockbuster anti-TNF biologic Humira(adalimumab) or a placebo.
Lilly is preparing to resubmit its new drug application (NDA) for the JAK1/2 inhibitor to the US FDA by the end of January. (Also see "Lilly/Incyte's JAK Inhibitor Baricitinib Poised For FDA Approval After All" - Scrip, 30 Aug, 2017.) That will kick off a six-month review by the agency, which rejected the original NDA and requested additional cardiovascular safety data for baricitinib earlier this year. (Also see "Baricitinib Complete Response May Put Lilly/Incyte Behind IL-6 Blockers In RA" - Scrip, 14 Apr, 2017.) The drug already is approved in the EU and Japan as Olumiant. (Also see "Lilly's Olumiant To Be EU's First RA JAK Inhibitor, But Pricing Is Key" - Scrip, 16 Dec, 2016.)
The new head-to-head pain data for baricitinib versus Humira and placebo come from a post-hoc analysis of the 1,305-patient Phase III RA-BEAM study, which enrolled people with RA who were not adequately treated with the standard-of-care first-line drug methotrexate.
Lilly Vice President of Immunology Peter Salzmann told Scrip that what was surprising in the new analysis was that while baricitinib showed an advantage over Humira in terms of improvement in RA symptoms as measured by ACR20 (a 20% or greater improvement), the difference between the company's oral drug and AbbVie's biologic was even greater in terms of the magnitude of improvement in pain and the speed at which patients reported pain relief.
Patients remained on methotrexate therapy, but were randomized for treatment with once-daily placebo once daily (n=488), 4 mg baricitinib once daily (n=487) or a 40 mg bi-weekly injection (n=330). Pain control during the first 24 weeks of the trial, as measured by a 0-100 mm visual analog scale (VAS) during each study visit, showed that baricitinib-treated patients achieved a 30% pain improvement at a median 1.9 weeks versus two weeks in the Humira group and 4.6 weeks in the placebo group.
Patients achieved a 50% pain improvement at a median of four weeks in the baricitinib arm of the study, 7.9 weeks in the Humira arm and 14 weeks in the placebo arm. A 70% improvement was seen at a median of 12.4 weeks in the baricitinib group, 20 weeks in the Humira group and 24 weeks in the placebo group. Patients without pain relief in the placebo arm at 24 weeks were switched to baricitinib.
Lilly also reported that patients reporting higher levels of pain at baseline had faster pain relief than those treated with Humira and placebo. That could be an important differentiator for patients who have higher pain levels regardless of the severity of other RA symptoms, because, as Salzmann noted, "pain is a big motivator to take action."
However, the executive said Lilly and the clinicians researching baricitinib are still investigating what caused the drug's "faster, deeper" effect on pain, which can't be explained by an improvement in arthritis symptoms alone. One theory put forward by baricitinib investigator Peter Taylor of the Kennedy Institute of Rheumatology at the University of Oxford, UK, is that inhibition of JAK reduces the activity of granulocyte-macrophage colony-stimulating factor (GM-CSF), which plays a role in pain.
Scrip caught up with Ironwood Pharmaceuticals Inc. Chief Commercial Officer Thomas McCourt during the ACR/AHRP meeting, after speaking with him following the approval of Duzallo(lesinurad and allopurinol) in August, to see how the gout drug's launch is going so far. (Also see "Duzallo Approval Opens Gout Opportunity For Ironwood" - Scrip, 21 Aug, 2017.)
The launch of Zurampic (lesinurad) at the end of 2015 primed the market for Duzallo. (Also see "AZ's Gout Drug Gets FDA Go-Ahead With Safety Caveats" - Scrip, 23 Dec, 2015.) Ironwood sees the combination product's launch as an important milestone for the lesinurad franchise, which was acquired from AstraZeneca PLC in April 2016, because it gives physicians more confidence about efficacy and safety. (Also see "Ironwood Buys AstraZeneca's Zurampic As Ideal Linzess Complement" - Scrip, 26 Apr, 2016.)
Zurampic was approved only when administered with allopurinol, because of renal side effects associated with monotherapy, which was a concern for doctors worried that gout patients would take the new drug and forget to take the generic standard-of-care drug. Duzallo eliminates that risk by combining the two treatments in one pill with better efficacy than either agent alone.
After about a month on the market, McCourt said prescribers "clearly see Duzallo as differentiated." He noted that primary care physicians are going through samples quickly, giving Ironwood some confidence that new prescriptions will be written for the combo pill.
"Early on, [with Zurampic] we had a lot of questions about renal toxicity," McCourt said. "Now, with launching Duzallo, the question is who do I prescribe it to?" Nurses, he noted, always know which patients are calling in to the office for allopurinol and prednisone prescriptions to take care of frequent gout flairs.
Payers are agreeing to reimburse the drug's cost, generally requiring a single "step edit," meaning gout patients must only fail allopurinol monotherapy before health plans in the US cover the medication.
McCourt notes that there are about 2m people in the US that qualify for Duzallo treatment and Ironwood only needs to reach about 6% to 8% of those patient to achieve the company's goal of $300m to $400m in peak sales.
Corbus Pharmaceuticals Holdings Inc. presented more detailed results during the ACR/AHRP meeting from its mid-stage clinical trials for its oral endocannabinoid-mimetic anabasum (JBT-101; formerly resunab) in dermatomyositis and systemic sclerosis – trials that support investment in additional studies, including a Phase III trial starting before the end of this year. Anabasum is designed to preferentially target the cannabinoid 2 receptor on activated immune cells and fibroblasts to resolve inflammation and halt fibrosis.
Norwood, Mass.-based Corbus initially reported Phase II results in systemic sclerosis – a disease with about 90,000 patients in the US and EU – at the ACR meeting in November 2016, which showed improvement in disease symptoms versus placebo in a 36-patient, placebo-controlled, 16-week clinical trial. (Also see "ACR 2016 Roundup: Remicade Copy Not So Similar; Mixed Sirukumab Results; Corbus’s Resunab Surge" - Scrip, 16 Nov, 2016.)
Data at this year's meeting were from the study's open-label extension (OLE) in which all patients were treated with anabasum. At 28 weeks of treatment with 20 mg dosed twice daily in the OLE, the modified Rodnan Skin Score (mRSS; a mean of 24 at baseline) fell by a mean of 8.4 points from baseline (p<0.0001). The company said 75% of patients achieved mRSS scores consistent with improved survival.
In dermatomyositis (about 70,000 patients in the US), Corbus reported top-line Phase II results in October and presented detailed data from the 22-patient, placebo-controlled trial at the ACR/AHRP meeting. (Also see "Pipeline Watch: Phase III Readouts For Cabozantinib, Topical Glycopyrronium" - Scrip, 23 Oct, 2017.) The primary endpoint was reduction in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores versus placebo with a 5-point or greater reduction considered medically meaningful.
Mean CDASI scores fell by 9.3 points in the anabasum treatment group and 3.7 points in the placebo group at 16 weeks (p=0.04) after patients took the drug or placebo for 12 weeks (20 mg once-daily for the first four weeks and twice-daily during weeks five through 12). There were no serious adverse events, and side effects – dry mouth, dizziness, dyspepsia, headache and increased appetite – were all considered mild or moderate. The company said 95% of the study participants (21 out of 22) enrolled in the OLE.
Corbus Chief Medical Officer Barbara White noted that the National Institutes of Health (NIH) provided most of the funding for the dermatomyositis trial, which was conducted in collaboration with the University of Pennsylvania. "It was a great trio; we were all happy" with the results, White said.
She noted that there will be another dermatomyositis study starting at some point in 2018. Corbus has not determined whether it will be pivotal study, but the company expects to evaluate anabasum's efficacy related to both the dermatological and muscle effects of the disease (the first Phase II focused only on the skin).
CEO Yuval Cohen told Scrip that Corbus has gotten "a lot of good FDA feedback" on the company's design for its Phase III systemic sclerosis study starting before the end of 2017. It will enroll about 340 patients and test two doses of anabasum versus placebo for a year with data expected around the end of 2019.
Before then, the company will have 12-month OLE results in systemic sclerosis and six-month OLE results in dermatomyositis. Also in 2018, Corbus plans to initiate another Phase II study examining anabasum in the reduction of pulmonary exacerbations in cystic fibrosis (CF); the first set of Phase II data in CF were reported in March. (Also see "Corbus Cystic Fibrosis Data May Justify Longer, Larger Study" - Scrip, 31 Mar, 2017.)
The earlier CF study was funded by the Cystic Fibrosis Foundation (CFF) and the company should learn next year whether the second mid-stage trial will have CFF funding. Either way, Corbus expects results from the new Phase II trial in 2019. The company raised $32.5m in a late October stock offering to fund its clinical trials and other expenses. (Also see "Finance Watch: NDA-Ready Impact Gets Commitment For Another $90m" - Scrip, 30 Oct, 2017.)
Samumed LLC, which is developing novel small molecule Wnt inhibitors for a variety of indications, presented Phase II results for its lead drug candidate SM04690, a local injection for the treatment of osteoarthritis (OA) of the knee, at the ACR/AHRP meeting.
San Diego-based Samumed's Chief Medical Officer Yusuf Yazici told Scrip that a higher dose of SM04690 is being tested now in the ongoing Phase II study and results from that dose will be reported around April or May. After discussions with the FDA, if the proof-of-concept study is positive across both doses, the company will initiate two Phase III studies in the second half of 2018 and seek approval around the end of 2019.
In patients treated with the first of the two Phase II doses, which was administered as a single intra-articular injection of SM04690, knee X-rays showed an increase in the medial compartment joint space width at 52 weeks. Patients also experienced pain reductions and improved knee function.
Yazici said benefits were maintained through six months and appeared to stabilize through one year post-treatment. That efficacy has to do with the drug's mechanism of action of inhibiting Wnt, which otherwise leads to cartilage reduction, bone creation and inflammation, he explained.
Samumed CEO Osman Kibar said the company will continue development of SM04690 on its own, but seek a partner for commercialization in the US after the Phase II program is completed. Samumed also will look for an ex-US partner at that time for development and commercialization outside the US.
The company also has Wnt inhibitors in early and mid-stage development for other indications, including SM04554 in androgenic alopecia, with a Phase III ex-US study kicking off in 2018. If the drug works in that trial, Samumed will conduct a second pivotal trial for hair loss in the US.
Other earlier-stage Wnt inhibitors include the inhaled candidate SM04646 in Phase I for idiopathic pulmonary fibrosis and well as the topical therapy SM04755, which is in Phase I for psoriasis now and going into Phase II in tendinopathy in 2018. A Phase I study for oral SM04755 in eight different solid tumors will enroll its first patient any day now.
To date, Samumed has been funded entirely by private investors, including family offices, sovereign funds and high net worth individuals. The company has largely operated in stealth mode since 2008, but plans to publish more of the science underlying its compounds in 2018 to build credibility as it prepares to approach development partners for SM04690 and other assets.
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