Chugai preps filings for IL-6 drug in rare disease, chasing Soliris

Chugai has the positive phase 3 data it needs to file IL-6-targeting antibody satralizumab for approval in neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune disease, next year.

The Japanese drugmaker now has two positive phase 3 studies backing the efficacy and safety of the antibody in the disorder, which causes inflammation of the optic nerves and spinal cord and leads to progressive deterioration in vision and motor function that in some cases can be fatal.

Despite treatment with immunosuppressants, sometimes in conjunction with steroids, patients with NMOSD typically suffer frequent relapses that exacerbate symptoms and can lead to them going blind and becoming wheelchair-bound.

There are no approved treatments for the disease, which is estimated to affect up to four people per 100,000, and it is sometimes misdiagnosed as multiple sclerosis.

The latest SAkuraStar data—reported at the ECTRIMS conference in Berlin—showed satralizumab as a monotherapy met the primary objective of significantly extending the time to first-relapse compared to placebo, and also reduced the overall risk of relapse. Chugai isn’t revealing the full data set just yet but says it will do so at the future medical conference.

The results back up the SAkuraSKY trial data reported in October that showed adding satralizumab (SA237) to standard therapy reduced the risk of these relapses by 62% compared to standard therapy plus placebo. After 48 weeks, almost 89% of patients on the drug were relapse-free, compared to 78% of the placebo group, and after 96 weeks the proportions were 66% and 59%, respectively.

The new data are also good news for Chugai’s strategic alliance partner Roche, which licensed worldwide satralizumab rights two years ago, with the exception of Japan, South Korea and Taiwan.

Chugai’s co-head of project and life cycle management, Yasushi Ito, said the company will “work diligently to prepare for regulatory filing so that we can offer a new treatment option to patients with NMOSD as soon as possible.” It’s estimated that the market for NMOSD drugs could be worth about $500 million a year.

Satralizumab may not be able to reach the market for NMOSD first, however, as Alexion is also in the final stages of developing its blockbuster anti-complement C5 drug Soliris (eculizumab) after a positive phase 3 trial, and said in September it was preparing to file for approval.

That lead may not prove decisive, however. Soliris’ data set has been generated exclusively in patients with anti-aquaporin-4 (AQP4) auto antibody-positive NMOSD, while Chugai’s monotherapy trial showed a benefit in both AQP4-positive and negative subjects. The Japanese company’s drug is also easier to administer, given as a monthly subcutaneous injection after an initial loading phase, while Soliris is administered every two weeks intravenously.

Meanwhile, other competition is waiting in the wings. Viela Bio has a CD19-targeting drug called MEDI-551 (inebilizumab) in phase 2/3 testing for NMOSD with results due next summer. The trial is testing an IV dose of the drug at baseline and after two weeks, then every 26 weeks thereafter.

It’s worth noting that the window of opportunity for all the drugs in development for NMOSD may also be fairly short, as Soliris is heading for patent expiries in the U.S. and EU in 2021 and 2020, respectively, after which cheaper biosimilars could reach the market.

https://www.fiercebiotech.com/biotech/chugai-preps-filings-for-il-6-drug-rare-disease-chasing-soliris

Altria drops as analysts say Juul stake ‘destroying value’

Shares of Altria Group (MO) dropped in morning trading after several Wall Street analysts voice the opinion that the price the company is paying for its 35% stake in Juul is a high cost that has the potential, as one put it, to “destroy value.”

BACKGROUND: On Thursday, Altria announced that it would invest $12.8B in Juul, taking a 35% stake in e-vapor company Juul Labs. “We are taking significant action to prepare for a future where adult smokers overwhelmingly choose non-combustible products over cigarettes by investing $12.8 billion in Juul, a world leader in switching adult smokers,” Altria CEO Howard Willard said in a statement. “We have long said that providing adult smokers with superior, satisfying products with the potential to reduce harm is the best way to achieve tobacco harm reduction.” Juul has drawn criticism over its products’ popularity with teens and the U.S. Food and Drug Administration previously announced plans to place restrictions on sales of flavored e-cigarettes. Juul also said it would restrict sales of nearly all its flavored pods to the internet, and stop most social media promotion to combat youth vaping. Altria previously said it would pull its pod-based e-vapor products from the market until approved by FDA. Altria’s investment in Juul comes on the heels of its announcement that it will take a 45% stake in cannabis company Cronos Group (CRON) and discontinue its MarkTen and Green Smoke e-cigarette products and its Verve oral nicotine.

JUUL STAKE ‘DESTROYING VALUE’: Citi analyst Adam Spielman downgraded Altria Group to Sell from Neutral, telling investors in a research note that he believes the Juul stake news is likely “destroying value,”  but that it is impossible to be sure as Altria has not revealed any financial details “despite the scale of the investment.” He added that the deal weakens Altria’s existing business, as it allows Juul to directly contact Altria’s current consumers, to try to persuade them to switch from Marlboro to Juul. Meanwhile, Morgan Stanley analyst Pamela Kaufman said Altria’s move comes at a high price, noting that the $38B valuation represents more than double the $16B valuation that JUUL received in an investment round last summer. Additionally, the analyst sees risk in Altria’s lack of operating control and the potential for further FDA regulation. Stifel analyst Christopher Growe called the $38B valuation “unusually high” and, in his view, a negative, as he believes the price offsets most of the future potential benefit, if not all, from the addition of Juul. Moreover, Growe said that at this premium valuation level, he is surprised that the company is not getting control of Juul and cannot get control over the next four years. Deutsche Bank analyst Steve Powers agreed, saying the deal is “not the holiday gift we’d hoped for.”

https://thefly.com/permalinks/entry.php/id2840691/CRON;MO-Altria-drops-as-analysts-say-Juul-stake-destroying-value

FDA approves Stemline’s Elzonris infusion for BPDCN treatment

The U.S. Food and Drug Administration approved Elzonris infusion for the treatment of blastic plasmacytoid dendritic cell neoplasm, or BPDCN, in adults and in pediatric patients, two years of age and older. “Prior to today’s approval, there had been no FDA approved therapies for BPDCN. The standard of care has been intensive chemotherapy followed by bone marrow transplantation. Many patients with BPDCN are unable to tolerate this intensive therapy, so there is an urgent need for alternative treatment options,” said Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. The labeling for Elzonris contains a Boxed Warning to alert health care professionals and patients about the increased risk of capillary leak syndrome which may be life-threatening or fatal to patients in treatment. The FDA granted the approval of Elzonris to Stemline Therapeutics. Stemline shares are down 46c, or 5%, to $8.22 in morning trading.
https://thefly.com/landingPageNews.php?id=2840709

Piper says Alexion early approval should help continue complement ‘dominance’

Piper Jaffray analyst Christopher Raymond notes that expectations were for Ultomiris to be approved in February, meaning today’s decision came roughly two months early, which will pull forward the timeline for Alexion’s market conversion from Soliris to Ultomiris. The earlier than expected approval, along with the “high bar Ultomiris has set,” positions Alexion to “continue its dominance in the complement space,” said Raymond. He maintains an Overweight rating and $177 price target on Alexion shares.
https://thefly.com/landingPageNews.php?id=2840717

FDA approves Alexion’s Ultomiris to treat PNH

https://thefly.com/landingPageNews.php?id=2840698

Perrigo hit after disclosing Irish tax bill

Perrigo Co. PLC PRGO, -21.63% shares fell in after-hours trading Thursday after the drug company disclosed that Ireland is attempting to collect a large tax bill. After closing at $52.36, their lowest close since 2010, shares fell more than 7% in some late trades. In a filing with the Securities and Exchange Commission, Perrigo said that the Irish Office of the Revenue Commissioners had decided that subsidiary Elan Pharma Ltd. paid an incorrect tax rate on proceeds from a 2013 sale of intellectual property to Biogen Inc. BIIB, -0.41% The Irish agency said that Elan should have paid a tax rate of 33% on the sale, but it paid 12.5%, leading to a bill of about 1.64 billion euros, not including interest or penalties. Perrigo said it plans to appeal the ruling, and that an outcome “could take a number of years.” “Perrigo strongly disagrees with both the basis on which Elan Pharma has been assessed and the methodology used to calculate the amount,” the company said in the filing, which described the action as “without merit” and “incorrect as a matter of law.” Perrigo stock has declined 39.9% this year through Thursday’s close, while the S&P 500 index SPX, +0.20% has lost 6.2%.

https://www.marketwatch.com/story/perrigo-discloses-irish-tax-bill-stock-declines-in-after-hours-trading-2018-12-20

Sarepta New Drug Application for Duchenne Approval

Sarepta Therapeutics, Inc. (NASDAQ:SRPT), a leader in precision genetic medicine for rare diseases, announced today that it has completed the submission of its rolling New Drug Application (NDA) seeking accelerated approval for golodirsen (SRP-4053), a phosphordiamidate morpholino oligimer engineered to treat those patients with Duchenne muscular dystrophy who have genetic mutations subject to skipping exon 53 of the Duchenne gene. Duchenne is a fatal genetic neuromuscular disorder affecting an estimated one in approximately every 3,500 – 5,000 males born worldwide.

The completion of the rolling submission for golodirsen includes data from the 4053-101 study assessing the safety, tolerability, pharmacokinetics and dystrophin expression of golodirsen in 25 boys with confirmed deletions of the DMD gene amenable to exon 53 skipping. The study demonstrated statistically significant results in favor of golodirsen on all biological endpoints, including properly exon-skipped RNA transcript using reverse transcription polymerase chain reaction, increase in quantity of dystrophin expression from baseline using Western blot and increase in dystrophin intensity as measured by immunohistochemistry.

If the golodirsen NDA is filed and granted accelerated approval, the companys ESSENCE study (4045-301) could serve as a post-marketing confirmatory study. ESSENCE, which is under way, is a global, randomized double-blind, placebo-controlled study assessing the safety and efficacy of golodirsen and casimersen, our exon 45 skipping therapy.

Golodirsen is a phosphordiamidate morpholino oligimer engineered to treat those patients with Duchenne muscular dystrophy (DMD) who have genetic mutations subject to skipping exon 53 of the DMD gene. Patients with a 53 mutation represent 8 percent of those with Duchenne.

https://www.marketscreener.com/SAREPTA-THERAPEUTICS-INC-11204214/news/Sarepta-Therapeutics-Completes-Submission-of-New-Drug-Application-Seeking-Approval-of-Golodirsen–27787263/