Sanofi’s hard-hit Lemtrada goes under EU review for fatal side effects

After a tough year in the competitive multiple sclerosis field, Sanofi’s Lemtrada could hardly afford another setback. But that’s exactly what it received last week.

On Friday, the European Medicines Agency (EMA) recommended temporary restriction of Lemtrada’s use as the agency reviews reports that the drug compromises patients’ immune systems and potentially leads to fatal side effects in the heart and blood vessels.

In its recommendation, the agency’s Pharmacovigilance Risk Assessment Committee said use of the intravenous drug should be limited only to relapsing-remitting MS that is highly active despite treatment with at least two disease-modifying therapies or where other DMTs cannot be used. In addition, the agency is weighing placing new safety warnings on Lemtrada’s label.

Once the EMA’s review is complete, the final findings will be submitted to the Committee for Medicinal Products for Human Use before a final decision is made by the European Commission. Lemtrada received EU approval in 2013.

The hurdle in Europe comes after a troubled year in which Lemtrada was flagged by the FDA for upping the risk of artery tears and stroke, and more challengers entered the packed MS market.

In November 2018, the FDA issued a safety warning for Lemtrada after reports of “rare but serious” cases of stroke and tears in the lining of head and neck arteries cropped up among Lemtrada patients shortly after receiving the drug. The FDA said 13 patients had reported such cases after the drug’s U.S. approval in 2014.

As part of its notice, U.S. regulators altered the drug’s prescribing label medication guide and existing black-box warning to reflect the reported health risks.

In late March, Merck KGaA’s Mavenclad received a long-delayed FDA approval, adding more pressure to Lemtrada’s flagging sales in a crowded field that includes Novartis’ Gilenya and Mayzent, Biogen’s Tecfidera and Tysabri along with Roche’s Ocrevus. In addition, Celgene recently resubmitted its FDA approval request for ozanimod, a treatment for relapsing MS.

And as competition and regulatory scrutiny have increased, Lemtrada’s sales have fallen. In fiscal 2018, Sanofi reported sales of the drug sank 15% from 2017 to land at €402 million euros ($454.6 million).

That poor showing followed a 2017 in which Lemtrada’s sales increased, but not up to analyst expectations. Sanofi has had to fend off the decline of its aging diabetes division and has leaned on its MS offerings in recent years.

Sanofi is hoping positive data from an eight-year clinical trial will help Lemtrada stay afloat in the market. Last October, the company rolled out phase 3 clinical data showing Lemtrada was still working in about half of relapsing-remitting MS patients eight years after their initial two treatment courses.

https://www.fiercepharma.com/pharma/sanofi-s-lemtrada-under-review-eu-for-fatal-side-effects-heart-blood-vessels

Supreme Court sends Allergan packing over Restasis tribal licensing strategy

Allergan has fought hard—and controversially—to protect its patents for blockbuster eye medicine Restasis with the help of a Native American tribe, but that effort seems to be reaching an end.

In a summary of Supreme Court orders for Monday, the Supreme Court refused to take up Allergan’s argument over a tribal licensing deal that involved transferring Restasis patents to the Saint Regis Mohawk Tribe and licensing them back. The move left in place a lower court’s ruling that the patent protection strategy is invalid.

An Allergan spokeswoman declined to comment.

The fight over Allergan’s tribal licensing deal has played out for about a year and a half. In September 2017, the drugmaker struck its deal with the Saint Regis tribe, aiming to sidestep a patent review at the U.S. Patent and Trademark Office on grounds that the tribe has “sovereign immunity” from such reviews.

But when Allergan inked the agreement, pharma watchers blasted it, saying it could further hurt the industry’s reputation as drugmakers faced swelling scrutiny over pricing. A group of U.S. senators wrote to Allergan CEO Brent Saunders saying that the move, paired with Allergan’s “social contract” on pricing, amounted to “hypocrisy.”

Still, Allergan stuck with the move, even when a U.S. Court of Appeals for the Federal Circuit ruled that it wouldn’t protect against reviews at the U.S. Patent and Trademark Office. Allergan and the tribe then took their arguments to the Supreme Court.

Separately, Allergan’s Restasis patents have been hit in federal court. In October 2017, a U.S. court piled on the pain with a ruling that Restasis’ patents were invalid; Allergan cut 1,400 jobs in response. Generic drugmakers are seeking to market copycats but haven’t yet won FDA approval. Last year, Restasis pulled in $1.26 billion, a 14% decline from 2017.

Meanwhile, Allergan also faces competitive threats to its top seller Botox, and it’s suffered from other recent setbacks, too. Last month, the company reported a phase 3 failure for closely watched depression drug candidate rapastinel.

https://www.fiercepharma.com/pharma/supreme-court-sends-allergan-packing-over-tribal-licensing-gambit

NILE study recommends Guardant Guardant360 assay in tissue testing

Guardant Health announced that the “positive results” from the NILE study, a head-to-head comparison of the Guardant360 assay to standard-of-care tissue testing for the identification of guideline-recommended biomarkers in first-line advanced non-small cell lung cancer patients, have been published in Clinical Cancer Research. The study adds new data regarding Guardant360’s high concordance to tissue testing to the abstract that was highlighted before the AACR Annual Meeting. The study adds to a “growing body of literature” demonstrating that using Guardant360 first for genomic biomarker detection in advanced NSCLC can increase the number of patients tested for guideline-recommended biomarkers.

https://thefly.com/landingPageNews.php?id=2892809

Janssen CAR-T Therapy Gets Euro Medicines Authority Priority Designation

PRIME (PRIority MEdicines) designation based on clinical study results evaluating safety and efficacy of novel CAR-T therapy in the treatment of patients with advanced relapsed or refractory multiple myeloma

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the European Medicines Agency (EMA) has granted a PRIME (PRIority MEdicines) designation for the company’s investigational B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, JNJ-68284528 (JNJ-4528). PRIME offers enhanced interaction and early dialogue to optimise development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.^[1]

‘The PRIME designation of this novel BCMA CAR-T therapy highlights the value of regulatory innovation in the European Union,’ said Sjaak Bot, Vice President, Head EMEA Regulatory Affairs at Janssen Biologics B.V. ‘We hope to bring this important advance to patients as quickly as possible and this PRIME designation, the first for Janssen, marks an important milestone towards potential market approval.’

The PRIME designation is based on results from the Phase 1/2 LEGEND-2 study (NCT03090659) evaluating LCAR-B38M CAR-T cells, sponsored by Nanjing Legend Biotech Co.,^[2] and the Phase 1b/2 CARTITUDE-1 study (NCT03548207) evaluating JNJ-4528, sponsored by Janssen and being conducted in collaboration with Legend Biotech USA Inc.^[3] Results from the LEGEND-2 study were presented at the American Society of Hematology (ASH) 2018 annual meeting.^[4] Results from the CARTITUDE-1 study will be presented in the future.

https://www.marketscreener.com/JOHNSON-JOHNSON-4832/news/Johnson-Johnson-Janssen-Announces-Investigational-CAR-T-Therapy-JNJ-68284528-Granted-PRIME-Desig-28426947/

Amgen announces Evenity is available for shipment in the U.S.

Amgen announced that EVENITY, or romosozumab-aqqg, is now available for shipment to wholesalers in the U.S. EVENITY was approved by the FDA on April 9 for the treatment of osteoporosis in postmenopausal women at high risk for fracture. Osteoporosis is a serious, chronic condition with no cure.
https://thefly.com/landingPageNews.php?id=2892761

Novartis says FDA accepts BLA for brolucizumab for AMD treatment

https://thefly.com/landingPageNews.php?id=2892780

Adverum offers late notice on FDA hold on lead gene therapy

The FDA has some questions for Adverum Biotechnologies about the CMC work related to their lead gene therapy for wet, age-related macular degeneration, and regulators have put a clinical hold on their clinical development program until they get some answers.

The Menlo Park, CA-based biotech $ADVM reported Monday as the market opened that the agency had placed a hold on their drug “in early April” and were now reviewing a response to their query, submitted last week. This was the first chance that investors got to hear about this news from the public company, which reserved word about the FDA action until after they noted they had a green light from the independent data monitoring committee for the recruitment of their second cohort of patients for ADVM-022.

This is their only clinical-stage program. But the news seems to be sitting well with its shareholders. The stock is up 7% in mid-afternoon trading.

The treatment involves aflibercept coding sequence which is delivered to the eye via a company-owned vector. Aflibercept is a drug delivered to the eye via injection, making any reduction in treatments something most patients would welcome.

Edward Nash at SunTrust says he’s been in touch with the executive crew at the biotech and noted that under the best case scenario the program would be delayed a month. That, obviously, could stretch out if the FDA takes more time to suss things out.

Adverum was formed out of Avalanche Biotechnologies’ acquisition of Paris-based Annapurna and their merger into a new gene therapy company following some trouble at Avalanche. Late last year the biotech abandoned their then lead, ADVM-043, after researchers determined it was having an insufficient effect on A1AT deficiency.

“We are working with the FDA to resolve this matter as quickly as possible,” said Adverum CEO Leone Patterson in a statement. “We are deeply committed to the development of our novel gene therapy ADVM-022 for patients with wet AMD. In the OPTIC trial, the DMC reviewed the safety data and unanimously agreed that we could proceed to dosing the second cohort. No patient has experienced an SAE, with a follow up period of up to five months. We look forward to sharing 24-week primary and secondary outcomes from the first cohort of patients at a scientific meeting in the second half of this year.”

Adverum Bio offers a late notification about FDA hold on lead gene therapy for wet AMD

Edit