No surprise: FDA hits Mylan and Biocon with CRL for follow-on copy of Lantus

The FDA has issued a complete response letter to partners Biocon and Mylan for their version of Sanofi’s blockbuster Lantus insulin, a development they say came as no surprise. Three months ago, the agency noted issues at the manufacturing site where it is produced.

 

A Mylan spokesperson acknowledged the CRL in an email Tuesday, saying the company has figured the delay into their launch plan for the product.

 

“Following submission of our Insulin Glargine application under the 505(b)(2) regulatory pathway, we had agreed with FDA to provide additional clinical data in support of the manufacturing site change from Bangalore to Malaysia. Hence, the recent CRL was anticipated and built into our plan."

The so-called “follow-on insulin glargine,” which references Lantus, has already been approved in Europe under the trade name of Semglee, but the partners have yet to satisfy the FDA that the manufacturing is all in order.

The partners in late February announced the FDA had issued a Form 483 with half a dozen observations during its first inspection of the Biocon plant in Malaysia where the insulin will be produced. Biocon said at the time that corrective actions were already underway.

That action was actually the second manufacturing glitch the partners have run into in their effort to get a Lantus copy to the U.S. market. The FDA issued a Form 483 last year for Biocon’s plant in Bangalore, India, where it makes the autoinjectors for its insulin products. It took about six months, but Biocon was able to get those issues resolved.

 

The CRL action is a break for Sanofi. Even though sales of Lantus have declined precipitously as the drugmaker has cut prices to compete, Lantus remains Sanofi’s top-selling product. All told, Lantus sales in the U.S. dropped 28.7% to €498 million ($602 million) during the first quarter. That caused worldwide sales of the product to fall 13.5% to €1,108 million ($1.3 billion).

The French drugmaker is not going to let those billions of dollars in sales go unchallenged. Sanofi last fall sued Mylan claiming the U.S. drugmaker has infringed 18 of its patents with its Lantus follow-on.

The CRL disclosure came the same day that Mylan and Biocon had good news to announce. They have received FDA approval to launch a biosim to one of the biggest drug targets in the U.S. market. Their biosimilar of Amgen's Neulasta, a drug that banked $3.9 billion in U.S. sales last year, will be launched shortly, they said.
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#ASCO18: AstraZeneca pioneer Lynparza scores with combo in prostate cancer

At last year’s American Society of Clinical Oncology annual meeting, AstraZeneca posted Lynparza data that would eventually make it the first in its class to break into breast cancer. This time around, it’s trying to grab the same crown in prostate cancer.

The British drugmaker, along with new partner Merck, on Monday touted results showing that adding Lynparza to Johnson & Johnson prostate cancer fighter Zytiga kept disease at bay for longer than Zytiga on its own. The combo staved off disease progression for 13.8 months, versus just 8.2 months for solo Zytiga.

The data are “really quite promising,” Dave Fredrickson, AstraZeneca VP and global head of oncology, told FiercePharma, noting that prostate cancer “is the No. 1 cancer in terms of incidence across the globe.”

“When you think about being a leader in oncology, really having programs in breast cancer, lung cancer, prostate cancer and GI cancers—those are the four largest. To be able to have these data in prostate cancer is incredibly important for us,” Fredrickson added.

AstraZeneca already leads its PARP competitors—Tesaro’s Zejula and Clovis’ Rubraca—when it comes to FDA approvals, thanks to the breast cancer nod it snagged after unveiling big phase 3 data at last year’s ASCO. And while the most recent prostate cancer results are from phase 2, they set Lynparza up to once again become the first PARP in a brand new market.

AstraZeneca will need big contributions from Lynparza if it hopes to crack into the top tier of cancer sellers, as Fredrickson predicted the company would. “We believe that we’re on a trajectory to be one of the top three global oncology players in the next five years,” he said. While immuno-oncology therapy Imfinzi—which bears a big new indication in lung cancer maintenance—is expected to kick in blockbuster sales, a potential miss in a closely watched first-line lung cancer study could dent its prospects.

Meanwhile, AZ’s PARP nemeses were busy at ASCO, too. Tesaro, for one, trumpeted data from a pairing of Zejula and Merck immuno-oncology star Keytruda in triple negative breast cancer that was “certainly in the ballpark of Lynparza,” Evercore ISI analyst Steve Breazzano wrote to clients.

“The merging … data suggest that combination of PARP + PD-1 potentially may add incremental, and deeper responses, though we’ll be looking for additional data (as well as AZN’s own combination data),” he said.

https://bit.ly/2JsqoRR

Ironwood: ‘Encouraging’ data from Phase 2b of GERD med trial

Ironwood Pharmaceuticals presented data from a double-blind, placebo-controlled, dose-ranging Phase IIb trial evaluating IW-3718 in persistent gastroesophageal reflux disease during a distinguished abstract plenary oral session at Digestive Disease Week 2018 in Washington, D.C. The data demonstrated that, compared to placebo, IW-3718 1500 mg plus a once a day proton pump inhibitor improved symptoms of heartburn severity in the overall population of GERD patients in the trial. Additionally, new data presented suggested a greater improvement in heartburn severity in the subset patient population of persistent GERD patients who also have erosive esophagitis, a severe inflammation and erosion of the esophagus. These findings build upon previously reported topline positive results from the trial, which demonstrated that IW-3718 1500 mg plus a PPI significantly reduced heartburn severity and showed reductions in frequency of regurgitation – two of the most bothersome and frequent symptoms of GERD – compared to a PPI alone. More than 50% of patients treated with IW-3718 1500 mg plus a PPI reported a clinically meaningful reduction in heartburn severity. Following these positive Phase IIb results, Ironwood expects to initiate Phase III trials during the third quarter of 2018. “These data are encouraging for physicians who continue to see their patients with GERD struggle with frequent and bothersome symptoms despite taking PPIs,” said Michael Vaezi, M.D., Ph.D. Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Director of the Center for Swallowing and Esophageal Disorders at Vanderbilt University Medical Center and an investigator for the study – who presented the data at DDW. “In addition to holding promise for patients with persistent GERD, these results show that IW-3718 also has potential in patients who also have erosive esophagitis despite PPI therapy – a serious condition that can cause severe damage and injury to the esophagus.”

https://bit.ly/2HkmpSd

Medtronic robot delay ‘clear positive’ for Intuitive Surgical: Cantor

Medtronic (MDT) today at its analyst meeting said it expects commercial launch of its surgical robot in fiscal 2020, which is roughly a year delay compared to the company’s prior expectations, Cantor Fitzgerald analyst Craig Bijou tells investors in a research note partially titled “ISRG’s Headstart Gets Bigger.” The analyst views the revised timing of the commercial launch of Medtronic’s robot as a “clear positive” for Intuitive Surgical (ISRG). With the commercial launches of the Medtronic and Johnson & Johnson (JNJ) robots at least 18 months away, Intuitive should continue to grow its global installed base, further advancing its global surgical robotics leadership position, Bijou writes. He reiterates his Overweight rating on the shares with a $510 price target. The stock in afternoon trading is up $8.46 to $486.39.

https://bit.ly/2LofFFj

Allergan says board refreshment continues to be ‘top priority’

Allergan issued the following statement in response to a public shareholder letter: “Allergan’s board of directors and management welcome input from all our shareholders, and take into account their views. Our board and management are committed to creating a world class biopharmaceutical and aesthetics business and driving shareholder returns. The conclusion of our recently completed strategic review is to create a more focused Allergan that concentrates on four therapeutic areas where we have leadership positions and depth and breadth of our products and pipeline, and to pursue a disciplined capital allocation strategy to generate value for shareholders. Our board has been active and aggressive in board refreshment with three new directors joining our board over the past 16 months, and board refreshment continues to be a top priority. The board also strongly believes in independent leadership as exemplified by the role of Chris Coughlin, our lead independent director, who was chosen as Director of the Year by the National Association of Corporate Directors in 2015. Mr. Coughlin brings over 30 years of biopharmaceutical industry experience to the Allergan board. Our number one priority continues to be executing on operational excellence and delivering strong results to drive long term shareholder value.”

https://bit.ly/2syOH7f

Merck said to be preparing for supply blackout amid Brexit

Merck is planning for the possibility of a temporary supply blackout when the U.K. leaves EU, and may stockpile as much as six months worth of goods, according to Bloomberg, citing a person familiar with the matter. The contingency plans include factoring in as much as two extra days of travel on routes between U.K. and EU destinations to allow for delays caused by document checks, source said.

https://bit.ly/2JcuTRf

Eisai, Biogen: Phase 2 Alzheimer’s med safe, well tolerated

Eisai (ESALY) and Biogen (BIIB) announced that elenbecestat was generally safe and well tolerated in a Phase II clinical study of the oral BACE inhibitor elenbecestat conducted in the United States, and the results demonstrated a statistically significant difference in amyloid beta levels in the brain measured by amyloid-PET. A numerical slowing of decline in functional clinical scales of a potentially clinically important difference was also observed, although this effect was not statistically significant. This study, a Phase II study of 70 patients, is the first study of a BACE inhibitor to show a statistically significant difference in amyloid beta in the brain while also suggesting a delay of clinical symptom decline in exploratory endpoints.Study 202 is a multicenter, randomized, double-blind, placebo- controlled parallel-group 18-month Phase II clinical study in patients with mild cognitive impairment due to Alzheimer’s disease, or mild to moderate dementia due to Alzheimer’s disease with confirmed amyloid pathology by PET screening. Seventy patients were randomized to four treatment arms receiving elenbecestat or placebo daily. During the study period, more than half the patients in the elenbecestat 5 mg and 15 mg arms were switched to the 50 mg arm for three months or more. The 50 mg treatment arm plus the group switched to the 50 mg arm are hereafter referred to as “50 mg total arm” with a mean duration of approximately 11 months on 50 mg per day. Elenbecestat demonstrated acceptable safety and tolerability profile through 18 months of study drug administration. In the elenbecestat 50 mg total arm, the six most common adverse events observed were contact dermatitis, upper respiratory infection, headache, diarrhea, fall, and dermatitis. No serious adverse reactions suggestive of hepatic toxicity were observed in this study. In addition to the safety objectives, the study assessed Abeta in the brain at 18 months as measured by amyloid PET as well as efficacy in terms of clinical symptoms, which were exploratory objectives in this study. The elenbecestat 50 mg total arm demonstrated a statistically significant difference in Abeta levels in the brain as measured by amyloid PET compared with placebo This is the first time in which a significant effect in Abeta in the brain using a BACE inhibitor was confirmed in a clinical study of patients with mild cognitive impairment through moderate Alzheimer’s dementia. CDR-SB was an exploratory endpoint to assess efficacy in terms of clinical symptoms. The study showed numerically less decline in CDR-SB for the elenbecestat 50 mg total arm as compared to placebo of a potentially clinically important difference, which was not statistically significant. Further, a similar magnitude and direction of differential in decline was observed in a post-hoc analysis of ADCOMS, Eisai’s newly developed assessment scale in the elenbecestat 50 mg total arm as compared to placebo. The study was not powered to show statistical significance compared to placebo on clinical symptoms.

https://bit.ly/2syZ6jf