FDA Action Alert: Merck and Xeris

June will eventually be a busy month for PDUFA dates, particularly the last week of the month, but the first two weeks are a bit sparse. Here’s a look at what’s on the U.S. Food and Drug Administration (FDA)’s calendar for the next two weeks.

Merck & Co., which had a very busy weekend at the American Society of Clinical Oncology(ASCO) Annual Meeting where it presented 140 abstracts, has a target action date of Monday, June 3 for a supplemental New Drug Application (sNDA) for Zerbaxa (ceftolozane and tazobactam) for adults with ventilated nosocomial (hospital-acquired) pneumonia. The drug is currently indicated in the U.S. for adults with complicated urinary tract infections, including pyelonephritis, caused by certain susceptible Gram-negative bacteria. It is also indicated, in combination with metronidazole, for adults with complicated intra-abdominal infections caused by certain Gram-negative and Gram-positive bacteria. The European Medicines Agency (EMA) is also reviewing Zerbaxa for this new indication.

Merck also has a target action date of June 10 for its supplemental Biologics License Application (sBLA) for Keytruda, the company’s blockbuster checkpoint inhibitor, as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy for first-line treatment of patients with recurrent or metastastic head and neck squamous cell carcinoma (HNSCC). The sBLA is built in part on data from the Phase III KEYNOTE-048 clinical trial. In that trial, Keytruda showed significant improvement in overall survival compared to standard of care as a monotherapy in patients whose cancers expressed PD-L1 with CPS greater than and equal to 20 and CPS greater than and equal to 1, and in combination with chemotherapy in the total patient population.

KEYNOTE-048 is a randomized, open-label Phase III clinical trial of Keytruda as a monotherapy or in combination, compared with the EXTREME regimen, as first-line treatment in 882 patients with recurrent or metastatic HSNCC. The dual primary endpoints were OS and PFS.

Head and neck cancer covers several different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. Most are squamous cell carcinomas that start in the squamous cells that make up the thin surface layer of the structures in the head and neck. In the U.S., it is estimated there will be more than 65,000 new cases of head and neck cancer diagnosed this year.

Xeris Pharmaceuticals has a target action date of June 10 for its NDA for its ready-to-use, room-temperature stable liquid glucagon rescue pen for the treatment of severe hypoglycemia—low blood sugar—in diabetes patients. The 505(b)2 NDA is based on positive data from multiple Phase III trials of the Xeris glucagon pen compared to currently marketed glucagon emergency kits.

“The FDA acceptance of our NDA for review, is an important milestone for Xeris,” said Paul R. Edick, Xeris’ chairman and chief executive officer in an October 2018 statement. “Compared to the current glucagon rescue option for people with diabetes who are at risk for severe hypoglycemia, the Xeris glucagon rescue pen would eliminate the need for reconstitution and dramatically simplify the preparation and administration process. We believe that our glucagon rescue pen has the potential to make an important difference in the lives of people with diabetes.”

https://www.biospace.com/article/fda-action-alert-merck-and-xeris/

Axcella Health (AXLA) Started by Goldman Sachs at Buy

Analysts at Goldman Sachs Group assumed coverage on shares of Axcella Health (NASDAQ:AXLA) in a report issued on Sunday. The firm set a “buy” rating on the stock.

Axcella Health (AXLA) Now Covered by Analysts at Goldman Sachs Group

So-Young Int’l (SY) PT Raised to $19 at Needham

https://www.streetinsider.com/Analyst+Comments/UPDATE%3A+So-Young+Intl+%28SY%29+PT+Raised+to+%2419+at+Needham+%26+Company/15565578.html

Follow-up studies often lacking for cancer drugs approved early

• Cancer drugs are often approved quickly by the Food and Drug Administration. In many cases, however, initial evidence of efficacy is never confirmed by studies testing for a survival benefit, according to new research published Tuesday in JAMA Internal Medicine.
• Just a fifth of cancer drug approvals between 1992 and early 2017 were eventually supported by clinical trials demonstrating an improvement in patient survival, researchers found. More than 40% of the time, the follow-up trials used to confirm early results tested the same surrogate measure, such as progression-free survival.
• Surging industry investment in oncology, coupled with the FDA’s desire to speed patient access to new cancer drugs, has resulted in a steady stream of approvals from the agency. Many of those drugs come with annual price tags stretching to six figures, making what patients are getting for the cost a critical question.

Cancer drugmakers are frequently the beneficiary of accelerated approvals from the FDA. Over the past four years, 17 of the 22 treatments granted an early, conditional OK by the agency were cancer treatments.

And under recently departed agency chief Scott Gottlieb, the FDA intensified its efforts to speed new therapies to market.

Gottlieb has defended the agency’s evolving approach to evaluating new cancer drugs, citing advances made in targeted therapy and in selecting the right patients for clinical study.

“We’re trying to balance competing needs,” he said in a speech last June. “The need for high degrees of statistical certainty, and the need for access to care.”

Soon after Gottlieb’s speech, the FDA published a list of surrogate endpoints used by the agency to approve cancer drugs, hoping be more transparent in how it decides to clear drugs without evidence of a survival benefit.

Two studies published this week in JAMA Internal Medicine, however, call into question that approach and argue for stricter management of how drugs are OK’d on an accelerated basis.

One, from researchers at Brigham and Women’s Hospital, Harvard Medical School and Queen’s University in Canada, details how few drugs approved on an accelerated basis ever end up being supported with survival data.

The study authors examined 93 cancer drug approvals for 64 separate products which were conditionally granted by the FDA between 1992 and May 31, 2017. Clearance was given based on surrogate measures like progression-free survival and overall response rate, which some have arguedare poorly correlated with clinical outcomes.

Just 19 of those approvals were eventually backed up by confirmatory studies showing an improvement in overall survival. Researchers found many of the studies used by drugmakers to confirm initial findings used surrogate endpoints as well — and, also in 19 cases, the same surrogate.

Notably, in only five cases was a conditional approval withdrawn as a result of negative confirmatory data.

The other JAMA study, conducted by researchers at Oregon Health and Science University, found that for 85 cancer drug indications the median response rate used to support approval was 41%. Fourteen of those approvals were granted based on data showing tumor response rates less than 20%.

Taken together, the two study findings “raise several doubts about the success of the accelerated approval process,” wrote Sarah DiMagno and colleagues from the University of Pennsylvania in commentary also published Tuesday.

They argue that the FDA should not permit drugmakers to use the same surrogate endpoint in confirmatory study, and call for more rapid withdrawal of approval if follow-up results show significant toxicity or no clinical improvement.

“The reliance on surrogate end points has real costs for patients and society,” they wrote. “Drugs with unproven effectiveness sell false hope to desperate patients, who are likely paying thousands of dollars out of pocket for them.”

Researchers in both studies did acknowledge, however, the wide range of differences in cancer types, differences that can change the context for use of a surrogate measure or for interpreting response rates.

https://www.biopharmadive.com/news/follow-up-studies-often-lacking-for-cancer-drugs-approved-early/555733/

Chronic disease biotech Morphic Holding files for an $86 million IPO

Morphic Holding, which is developing oral small-molecule integrin therapeutics for various chronic diseases, filed on Thursday with the SEC to raise up to $86 million in an initial public offering.

The Waltham, MA-based company was founded in 2014 and booked $9 million in collaboration revenue for the 12 months ended March 31, 2019. It plans to list on the Nasdaq under the symbol MORF. Morphic Holding filed confidentially on April 12, 2019. Jefferies, Cowen, BMO Capital Markets and Wells Fargo Securities are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: MORF

https://www.renaissancecapital.com/IPO-Center/News/63446/Chronic-disease-biotech-Morphic-Holding-files-for-an-$86-million-IPO

Schizophrenia biotech Karuna Therapeutics files for a $75 million IPO

Karuna Therapeutics, a Phase 2 biotech developing therapies for schizophrenia and other CNS disorders, filed on Friday with the SEC to raise up to $75 million in an initial public offering.

The Boston, MA-based company was founded in 2009 and plans to list on the Nasdaq under the symbol KRTX. Karuna Therapeutics filed confidentially on March 29, 2019. Goldman Sachs, Citi and Wells Fargo Securities are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: KRTX

https://www.renaissancecapital.com/IPO-Center/News/63472/Schizophrenia-biotech-Karuna-Therapeutics-files-for-a-$75-million-IPO

Illinois To Become 11th State To Legalize Recreational Marijuana

Illinois lawmakers approved the legalization of non-medical marijuana and sent the measure Friday to Gov. J.B. Pritzker who is expected to sign it, making the state the 11th in the country to allow recreational cannabis use.

What To Know

The legislation would allow residents 21 and older to legally be in possession of 30 grams of cannabis, 5 grams of cannabis concentrate or 500 milligrams of THC in a cannabis-infused product. Nonresidents could possess 15 grams of cannabis. Pritzker, who became governor in January, included legalization of marijuana in his platform when campaigning last year.

Pritzker also was pushing for the measure for financial reasons. He had banked on licensing and tax revenue to balance the state’s budget.

The House passed the bill Friday after the Senate approved it on Thursday.

Illinois would become the first state to legalize adult-use, or recreational, cannabis use through a proposal initiated in the legislature, rather than being required to do so by a voter initiative.

Why It’s Important

The measure also calls for expungement of the records of people with prior convictions for possession of less than 30 grams of cannabis. It also calls for taxation of cannabis sales based on concentration.

It also decriminalizes home growing of small amounts of cannabis – replacing jail time with a fine – and allows home cultivation of small amounts for medical marijuana patients.

“This is a great day for the people of Illinois who soon will be able to exercise their right to wellness through access to safe and regulated cannabis,” Ben Kovler, CEO of Green Thumb Industries Inc GTBIF 6.05% told Benzinga. “The benefits of adult-use legalization are many: much-needed tax revenue, regulation to ensure safe products, criminal justice reforms to counteract the failed war on drugs, and an alternative to opioids and alcohol.”

https://www.benzinga.com/markets/cannabis/19/05/13843713/illinois-to-become-11th-state-to-legalize-recreational-marijuana