Aldeyra commences late-stage study of reproxalap in allergic conjunctivitis

Enrollment is underway in a Phase 3 clinical trial, INVIGORATE, evaluating Aldeyra Therapeutics’ (NASDAQ:ALDX) topical ocular reproxalap in patients with allergic conjunctivitis.

The primary endpoint of the 120-subject study is ocular itching score compared to vehicle (placebo). The estimated completion date is September.

https://seekingalpha.com/news/3533035-aldeyra-commences-late-stage-study-of-reproxalap-in-allergic-conjunctivitis

Evoke Pharma up 19% premarket on FDA acceptance of Gimoti refiling

The FDA has accepted for review Evoke Pharma’s (NASDAQ:EVOK) resubmitted marketing application for Gimoti (metoclopramide) nasal spray for the relief of symptoms in adult women with acute and recurrent diabetic gastroparesis.

The agency’s action date is June 19.

The company received a CRL in August 2019 citing pharmacology and quality issues.

Shares up 19% premarket on average volume.

https://seekingalpha.com/news/3533049-evoke-pharma-up-19-premarket-on-fda-acceptance-of-gimoti-refiling

Analyst action, Jan. 21

Accuray (NASDAQ:ARAY) initiated with Buy rating and $9.50 (190% upside) price target at BTIG Research.

Arrowhead Pharmaceuticals (NASDAQ:ARWR) initiated with Underperform rating with a $32 (43% downside risk) price target at SVB Leerink. At JPM20, CEO Christopher Anzalone said that its current valuation puts the company “out of reach” for most suitors, adding that there is no “alignment” with any potential acquirer considering the size of the check needed to ink a deal. Shares down 4% premarket.

Selecta Biosciences (NASDAQ:SELB) initiated with Outperform rating at William Blair.

Anika Therapeutics (NASDAQ:ANIK) upgraded to Buy with a $61 (34% upside) price target at Sidoti.

Owens & Minor (NYSE:OMI) upgraded to Outperform with a $9 (63% upside) price target at Baird. Shares up 6% premarket.

Gilead Sciences (NASDAQ:GILD) downgraded to Neutral at Guggenheim.

Iterum Therapeutics (NASDAQ:ITRM) downgraded to Sell at Gabelli.

https://seekingalpha.com/news/3532977-leerink-sees-43-downside-in-arrowhead-in-premarket-analyst-action

Novavax up 59% premarket on mystery respiratory virus in China

Vaccine developer Novavax (NASDAQ:NVAX) is up 59% premarket on robust volume in apparent reaction to the spread of an unknown respiratory virus in China that has killed six people to date.

Buying appears to have spread to Inovio Pharmaceuticals (NASDAQ:INO) (+13%) and BioCryst Pharmaceuticals (NASDAQ:BCRX) (+6%).

https://seekingalpha.com/news/3533042-novavax-up-59-premarket-on-mystery-respiratory-virus-in-china

Congress Considers Bill to Address Medicare Late Penalties, Coverage Gap

Some 10,000 Americans turn 65 every day and become eligible for Medicare, but enrollment mistakes can subject them to a lifetime of late penalties, as well as a months-long coverage gap.

Legislation that would fix these problems was one of the bills discussed at a hearing held by the House Energy & Commerce Health Subcommittee 2 weeks ago. Although the panel focused on how the bipartisan Beneficiary Enrollment Notification and Eligibility Simplification (BENES) Act impacts Medicare patients, it also affects their physicians.

Under the current enrollment system, beneficiaries who don’t sign up for Medicare’s Part B outpatient coverage when they’re first eligible — and don’t qualify for an exception — can join only in January through March. Coverage begins the following July. While they’re waiting for coverage to kick in, most cannot purchase other health insurance. As a result, the rules delay Medicare coverage for thousands of people a year, according to Congressional Budget Office estimates.

Some may mistakenly assume they can skip Part B because they have, for example, retiree coverage or a COBRA policy from a former employer or one purchased through the Affordable Care Act’s marketplaces. But in many cases, once an insurer discovers that a beneficiary should have been covered under Part B, the plan can require a provider to refund payments received after the patient became Medicare eligible, said Fred Riccardi, president of the Medicare Rights Center, a consumer advocacy group.

“Then the patient could be on the hook for the services provided, and we’ve seen that happen,” Riccardi said, after testifying before the subcommittee.

The legislation would revise these rules for the first time in 5 decades. It would require the Centers for Medicare & Medicaid Services and the Social Security Administration to notify people before their 65th birthday about their Medicare eligibility. Currently, the federal government only contacts people receiving Social Security benefits when it’s time to join Medicare.

It would also move the January-through-March enrollment window to the fall, to coincide with the enrollment period for drug coverage and Medicare Advantage. And it would eliminate the July effective date.

Better-informed beneficiaries would also be able to avoid the permanent penalties applied when they delay signing up for Part B for 12 or more months after they become Medicare eligible. In 2018, about 760,000 people were paying a late penalty tacked onto their monthly Part B premium, increasing their costs an average of nearly 30%, according to the Congressional Research Service.

The American Medical Association says it is concerned about access and coverage for Medicare beneficiaries who do not have Part B coverage, as is the legislation’s sponsor, California Democrat Raul Ruiz, MD, who is also an emergency medicine physician.

“Too often, seniors don’t know when to enroll in Medicare Part B, and their late enrollment leads to higher out-of-pocket costs,” Ruiz said last week. “That’s why I introduced the BENES Act, which would help ensure that seniors can keep seeing their doctors by eliminating gaps in coverage, strengthening the notification process for enrollment, and aligning the open enrollment timeline with other parts of Medicare.”

The legislation, first introduced in 2016, is supported by 95 disparate organizations, including the AFL-CIO and other unions, health insurance companies, AARP, and patient advocacy and provider groups.

Questions about Part B enrollment are the most frequent reason Medicare beneficiaries call the center’s national helpline, Riccardi told the committee. If they don’t qualify for one of Medicare’s limited financial assistance or exception criteria, the center encourages them to ask their providers to reduce or waive the bill. That’s a decision physicians may be reluctant to make.

Rep. Michael Burgess, MD (R-Texas), the subcommittee’s ranking member, called the bill “well-intentioned,” yet he has some reservations: “We want our health system working better for individuals but we also know from the Congressional Budget Office that this bill comes at a significant cost,” he said during the hearing.

“About 3% of new enrollees would receive Medicare benefits sooner than under current law,” CBO reported last September. “These additional months of Medicare coverage would increase direct spending by $375 million over the 2019-2029 period.”

https://www.medpagetoday.com/publichealthpolicy/medicare/84437

Phage Therapy Firm APT Lands DoD Contract for Antibiotic Alternative

The Department of Defense has awarded Adaptive Phage Therapeutics a $10.2 million contract to help advance its experimental therapy for the treatment of multidrug-resistant infections.

Gaithersburg, MD-based Adaptive Phage Therapeutics (APT) says it will pursue a two-year multi-site clinical trial as it looks to get the OK from the FDA, which considers phage to be “Generally Regarded as Safe” and has identified phage therapy as a potential alternative to antibiotics.

Phages are bacterial viruses that destroy targeted bacteria—including those which have become resistant to antibiotics—and APT is developing its phage collection, “PhageBank,” to do just that.

According to the company, PhageBank is a library of polymicrobial broad-spectrum phages that can be matched to a specific pathogen. It is used with a companion diagnostic to select the best option for each patient.

“PhageBank incorporates a built-in feedback loop in which any uncovered bacteria are captured as source material for additional phage discovery. The additional phages enrich PhageBank and increase the spectrum of coverage, offering an effective response to evolving bacterial resistance,” explains APT CEO and co-founder Greg Merrill.

Since acquiring rights to PhageBank in 2017 from the US Navy, APT has provided patients access to the therapy under compassionate use.

Now, the company is working toward submitting the necessary data to the FDA in order to begin clinical trials in humans. If given the OK, APT plans to recruit patients with bacterial infections across three study sites in the US over the next 90 days. It will then quickly expand to a fourth site, Merrill tells Xconomy.

“Over the term of the program, APT’s effort is expected to expand terms of the variety of clinical indications and variety of pathogens,” he says. Though further details are undisclosed, the company says the market for the antibiotic alternative could be in excess of $4 billion for its first four planned indications.

“Phages have existed and co-evolved with bacteria over the past 3.8 billion years. There is a practically unlimited number of phages on earth,” he explains. And phages continue to evolve, which Merrill says enables “a broad and continually updated universe of potential options for patients with multi-drug resistant infections.”

The use of phage therapy to treat bacterial infections was first explored in the 1920s, Merrill says, though the emergence of antibiotics put development on the backburner. Today, as the threat of antibiotic resistance grows, however, so has the interest in phage therapy.

“Recent breakthroughs by APT and its collaborators at the biodefense directorate of the US military in bioinformatics, rapid phage-bacteria isolation and matching, and phage purification methods, enable both the rapid administration of phage therapy and a personalized solution tailored to a patient’s individual infection,” says Merrill.

APT in October last year raised approximately $7 million. Investors included Alexandria Venture Investments and an unnamed health care delivery network and New York Stock Exchange-listed life sciences company.

https://xconomy.com/national/2020/01/15/phage-therapy-firm-apt-lands-dod-contact-for-antibiotic-alternative/

FDA Action Alert: Epizyme and Merck

January isn’t a particularly busy month for PDUFA dates for the U.S. Food and Drug Administration (FDA), with only two scheduled for the month. Here’s a look.

Epizyme’s Tazemetostat for Sarcoma

Cambridge, Massachusetts-based Epizyme has a target action date of January 23 for its tazemetostat. The New Drug Application (NDA) is for metastatic or locally advanced epithelioid sarcoma patients not eligible for curative surgery. The drug is under the FDA’s Priority Review.

The NDA is largely based on data from an ongoing Phase II trial of the drug in a 62-patient cohort with epithelioid sarcoma. Tazemetostat is an oral potent, first-in-class EZH2 inhibitor. It is being evaluated as a monotherapy in specific molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors, as well as in patients with follicular lymphoma, both with and without EZH2 activating mutations.

The drug is also being evaluated as a combination treatment for patients with diffuse large B-cell lymphoma.

In order to garner full approval, Epizyme indicated in July it would initiate a global confirmatory trial, which would compare tezemetostat in combination with doxorubicin compared to placebo plus doxorubicin in about 150 patients. The primary efficacy endpoint would be progression-free survival, with secondary endpoints of overall survival, disease control rate, overall response rate and duration of response.

On December 18, 2019, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 11 to 0 in favor of recommending tazemetostat for this indication. Epithelioid sarcoma is a rare and aggressive soft tissue sarcoma marked by a loss of the INI1 protein. They are usually diagnosed in people between the ages of 20 and 40 years of age, and typically patients do not live past five years from diagnosis.

“We are incredibly pleased by ODAC’s unanimous support of the benefit-risk of tezemetostat in ES, and we appreciate the tremendous support received from sarcoma physicians and their medical teams, advocates, caregivers and most notably, patients with ES,” said Shefali Agarwal, Epizyme’s chief medical officer.”

Also, on December 18, 2019, the company submitted its NDA for tezemetostat for relapsed or refractory follicular lymphoma (FL), with or without EZH2 activating mutations, in patients who have received at least two prior lines of systemic therapy.

Merck’s Dificid for C. Diff Infections

Merck has a target action date of Jan. 24 for its Dificid (fidaxomicin) for oral suspension, and a supplemental NDA (sNDA) for a new indication for use of Dificid tablets and oral suspension for the treatment of Clostridium difficile (C. diff) infections in children aged six months are older. Both applications are under Priority Review.

Dificid is a macrolide antibacterial drug indicated in adults for treatment of C. diff-associated diarrhea (CDAD). C. diff is one of the most common causes of healthcare-related infections in U.S. hospitals, causing about 500,000 infections each year. It is associated with about 29,000 deaths within 30 days of individual diagnosis.

In October 2019, when the FDA accepted the submissions, Nicholas Kartsonis, senior vice president, Clinical Research, infectious diseases and vaccines, Merck Research Laboratories, said, “Evidence indicates the increasing incidence of C. difficile-associated diarrhea among hospitalized children. The filings for the pediatric indication for the new investigational oral suspension formulation of Dificid, as well as for Dificid tablets, underscore Merck’s focus and dedication to developing infectious disease treatments for those with unmet needs.”

The sNDA is built mostly on data from the Phase III SUNSHINE trial, which the company presented at IDWeek 2018 in San Francisco.

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