Lannett Restructuring Cody Laboratories Unit

Lannett Company, Inc. (LCI) today announced a restructuring and cost reduction plan of its subsidiary, Cody Laboratories (Cody), a developer and manufacturer of pain management active pharmaceutical ingredients (APIs).  The plan is expected to generate annualized cost savings of approximately $10 million and be substantially completed by December 2018.

“In recent years the regulatory and competitive landscape for pain management APIs has changed, extending Cody’s timeline to profitability and causing us to revise our plan for this business,” said Tim Crew, chief executive officer of Lannett.  “We determined the substantial continuing investment to attain the size and scale necessary to become a broad competitive force in that space was inconsistent with our renewed focus on our core business, where we see a great deal more near-term opportunities to grow high value assets.  Nevertheless, Cody continues to offer intriguing vertical integration opportunities.  We remain committed to investing in Cody’s operations, albeit in a more targeted and selective manner.  Savings that result from implementation of the restructuring and cost reduction plan will be invested in the opportunities and initiatives mentioned above.  We have also begun evaluating strategic alternatives to unlock even more value from Cody.”

As part of Cody’s restructuring, the company intends to transfer production of finished dosage liquid pharmaceutical products to its Carmel, New York facility, discontinue the manufacture of less profitable API products and rationalize the API product development program.  These actions are estimated to ultimately result in the reduction of approximately 50 positions at Cody.

The company estimates that it will incur approximately $5 million of total costs to implement the plan, comprised primarily of severance and employee related costs.  In addition, the company may incur non-cash impairment charges related to Cody’s facility, equipment and other plant-related assets.

https://yhoo.it/2tUAyAS

AbbVie says it will appeal $448 million antitrust judgment

AbbVie Inc. says it will appeal a $448 million judgment filed by the Federal Trade Commission, alleging that the pharmaceutical manufacturer and its partner overcharged consumers for a testosterone drug.

“We are disappointed by the ruling. We believe our conduct was lawful and the damages award is improper. We intend to appeal,” said an AbbVie spokeswoman, Toni Haubert in an emailed statement to MarketWatch.

In 2014, the FTC charged that Chicago-based AbbVie and its partner Besins Healthcare Inc. blocked consumer access to lower-cost versions of the testosterone replacement drug AndroGel.

The FTC accused AbbVie of using “sham litigation” to maintain its monopoly. AbbVie has previously denied the allegations and the breakdown of relief between AbbVie and Besins wasn’t immediately clear. “This decision is a double victory, both for patients who rely on AndroGel and for competition more broadly,” said FTC chairman Joe Simons in a statement on Friday.

“It sends a clear signal that pharmaceutical companies can’t use baseless litigation to forestall competition from low-cost generics.”

The decision handed down in the U.S. District Court for Eastern Pennsylvania is the largest monetary award in a litigated FTC antitrust case, the agency said.

AbbVie stock ABBV, +0.24% closed up 0.2% to $92.65 on Friday. AbbVie shares are down 4.2% this year, while the S&P 500 index SPX, +0.08% gained 1.7%, and the Dow Jones Industrial Average DJIA, +0.23% lost 1.8%.

https://on.mktw.net/2KlWHDx

Biotechs with July FDA dates

Biotech stocks had a fairly decent run in June, with the iShares NASDAQ Biotechnology Index (ETF) IBB 1.73% advancing about 3.5 percent through June 22 compared to the S&P 500’s 1.8-percent gain.

Presentations at two conferences, the American Society of Clinical Oncology’s annual meeting and the European Hematology Conference, created extreme volatility in the space. Biotech stocks were supported to some extent by an increase in market volatility due to the sector’s defensive stature.

For potential profit from volatility in the biotech space, stay tuned for the following PDUFA catalysts expected in the month of July:

Bristol-Myers Squibb’s IO Combo Awaits FDA Verdict For Colorectal Cancer

• Company: Bristol-Myers Squibb Co BMY 0.07%.
• Type of Application: supplemental biologics license application.
• Candidate: Opdivo in combination with Yervoy.
• Indication: metastatic colorectal cancer.
• Date: July 10.

The FDA accepted the sBLA for the combo on March 27, 2018 for treating adults with microsatellite instability-high, or mismatch repair deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin and irinotecan.

The application was granted priority review status as well as breakthrough therapy designation.

The application was submitted based on the CheckMate-142 study.

Checkmate-142 is a non-randomized, multi-arm Phase II study that evaluates Opdivo alone or in combination with other anti-cancer drugs for colorectal cancer.

Will FDA Go Against Panel Recommendation On Insys’ Pain Drug?

• Company: Insys Therapeutics Inc INSY 1.76%.
• Type of Application: NDA.
• Candidate: Buprenorphine sublingual spray.
• Indication: moderate-to-severe acute pain.
• Date: July 28.

The NDA was accepted for review based on a pivotal trial that met its primary efficacy endpoint.

A FDA panel that met May 22 recommended denying Insys’ NDA for the pipeline candidate.

DURECT’s Schizophrenia Drug Before FDA

• Company: DURECT Corporation DRRX 1.27%.
• Type of Application: NDA.
• Candidate: RBP-7000.
• Indication: schizophrenia.
• Date: July 28.

DURECT, which has assigned patents for its RBP-7000 to U.K.-based biotech INDIVIOR PLC/S ADR INVVY 2.19%, said the FDA accepted the application in December.

DURECT, which has already received an upfront payment of $12.4 million, stands to earn incremental $5 million contingent on FDA approval for RBP-7000.

RBP-7000 is once-monthly injectable risperidone for treating schizophrenia.

FDA To Rule On Progenics’ Rare Neuroendocrine Tumor Drug

• Company: Progenics Pharmaceuticals, Inc. PGNX 0.74%.
• Type of Application: NDA.
• Candidate: Azedra.
• Indication: rare neuroendocrine tumors.
• Date: July 30.

The review period was extended by three months from the original PDUFA date of April 30, as the FDA sought additional time to review the chemistry, manufacturing and controls information submitted by the company.

Azeda is used for treating patients with malignant, recurrent and/or unresectable pheochromocytoma and paraganglioma.

AbbVie-Neurocine Gear Up For Gain On Pain Drug

• Company: Neurocrine Biosciences, Inc. NBIX 1.05% and AbbVie Inc ABBV 0.24%.
• Type of Application: NDA.
• Candidate: Elagolix.
• Indication: endometriosis-associated pain.
• Date: The third quarter of 2018; based on the three-month extension in the review period announced by the FDA on April 10, the decision could come in July or early August.

The NDA was submitted based on data from the largest prospective randomized clinical trials conducted for endometriosis in about 1,700 women with moderate-to-severe endometriosis-associated pain.

Elagolix is a gonadotropin-releasing hormone receptor antagonist and is an orally administered, short-acting molecule that blocks endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland, according to the companies.

Adcom Meeting Schedule

FDA’s Pulmonary-Allergy Drugs Advisory Committee is set to discuss GlaxoSmithKline plc (ADR) GSK 1.87%‘s sBLA for mepolizumab injection, which is evaluated as an add-on treatment to inhaled corticosteroid-based maintenance treatment for the reduction of exacerbations in patients with chronic obstructive pulmonary disease.

https://bit.ly/2tV1wZa

Biotech week ahead, July 2

Biotech stocks came under pressure earlier in the week, weighed down by negative trial results, mixed FDA verdicts and overall pessimistic broader market sentiment, but recovered in the last two sessions. Yet the iShares NASDAQ Biotechnology Index (ETF) IBB 1.73% ended the week marginally lower.

Can the sector bounce back? Stay tuned to the following catalytic biotech events in the coming week.

Medical, Biotech, Health Care Conferences

• The International Symposium on Pediatric Neuro-Oncology: June 30-July 3 in Denver, Colorado.
• 34th Annual Meeting of the European Society of Human Reproduction and Embryology: July 1-4 in Barcelona, Spain.
• U.K. Radiological and Radiation Oncology Congress 2018: July 2-4 in Liverpool, England.
• 11th FENS Forum of Neuroscience: July 7-11 in Berlin, Germany.

Clinical Trial Results

NewLink Genetics Corp NLNK 1.24% is scheduled to release updated Phase 1 data for its indoximod in combination with chemotherapy and radiation to treat diffuse intrinsic pontine glioma at the ISPNO on July 1.

Zogenix, Inc. ZGNX 2.2% will release Phase 3 data for its ZX008 that is being evaluated in Study 1504 for Dravet syndrome in late June or early July.

Pending Releases From The First Half Of 2018

Acorda Therapeutics Inc ACOR 3.99% is due to release Phase 2 data for BTT1023 in primary sclerosing cholangitis.

Roche Holdings AG Basel ADR Common Stock RHHBY 1.39% will release Phase 3 data for its Tecentriq in combo with chemotherapy using Carboplatin and Abraxane based on the Impower132 study. The combo is being tested for squamous non-small cell lung cancer.

Novartis AG (ADR) NVS 3.48% is scheduled to release Phase 2 data for LJN452 to treat non-alcoholic steatohepatitis.

Apellis Pharmaceuticals Inc APLS 3.24% is due to release Phase 2 monotherapy data for its subcutaneously administrated APL-2 for auto-immune hemolytic anemia.

Novo Nordisk A/S (ADR) NVO 1.41% will present Phase 3 data for its semaglutide oral formulation for Type 2 diabetes. The company will also release Phase 3 data for its Somapacitan, which is being evaluated in the REAL 3 study for adult growth hormone deficiency.

Cara Therapeutics Inc CARA 0.62% is scheduled to present Phase 1 top-line data for its chronic kidney disease-associated pruritus treatment candidate Korsuva.

Zynerba Pharmaceuticals Inc ZYNE 0.1% is due to release Phase 1 data for its ZYN001,evaluated for Tourette syndrome.

Celsion Corporation CLSN 4.84% is due to release Phase 1b data for its GEN-1 in ovarian cancer.

CTI BioPharma Corp CTIC 4.96% is slated to release an interim analysis of Phase 2 data for Pacritinib in the treatment of myelofibrosis.

Aclaris Therapeutics Inc ACRS 4.23% is scheduled to release Phase 2 top-line data for its ATI-502 AA-202 in a topical application that’s being evaluated for alopecia areata.

Titan Pharmaceuticals, Inc. TTNP 0.93% will release Phase 1/2 data from the first patient cohort for the Ropinirole implant in the treatment of Parkinson’s disease.

Asterias Biotherapeutics Inc AST 10% and BioTime, Inc. BTX 1.48% are scheduled to release further readouts of Phase 1/2 data on their cervical spinal cord injury treatment option AST-OPCI, which was evaluated in a study dubbed SCiSTAR.

https://bit.ly/2KmgDGi

US Health Sec pressed to OK newborns screening for fatal genetic disease

Roughly once a day in the United States, a child is born with a fatal genetic disorder that destroys motor neurons in the brain stem and spinal cord. In its worst and most common form, spinal muscular atrophy (SMA) kills children when they are still toddlers, as their respiratory muscles fail.

But 18 months ago, the Food and Drug Administration approved a first, promising treatment: a drug that restores production of a key protein missing in SMA. Now, SMA advocacy groups and members of Congress are urging Secretary of Health and Human Services (HHS) Alex Azar to recommend that all 4 million infants born in the United States each year be tested for SMA. They argue that affected children should be identified and treated when the new drug likely helps the most—before neurons die.

By law, Azar faces an 8 July deadline, but such deadlines have been missed in the past. And although an advisory panel voted in February in favor of screening all newborns, some of its experts dissented. They noted that key studies of the new treatment—a drug called nusinersen (marketed as Spinraza by Biogen of Cambridge, Massachusetts)—are still ongoing, involve small numbers of children, and are unpublished.

But delay “would be a tragedy for children born in the interim who may benefit from screening because they will miss the window for receiving treatment when it is most effective,” 14 members of the House of Representatives wrote to Azar last month, urging speedy approval. An HHS spokesperson says Azar is “still reviewing this important issue.”

Checking for the SMA mutation in a drop of blood would cost $1 to $5 per newborn (although the drug itself costs $750,000 for the first year and $350,000 annually after that). But there’s a high bar for adding a disorder to the 34 conditions for which screening is recommended. Among other criteria, data must show that outcomes improve if treatment begins before symptoms appear. In this case, the key data come from an ongoing, Biogen-sponsored trial called NURTURE in which 25 newborns with confirmed SMA got the drug before symptoms developed. In July 2017, when the oldest baby had been followed for 25 months, all the children were still alive, none were ventilator-dependent, and those old enough sit up without support could do so—an achievement unheard of in babies that die early from SMA.

But those striking results have not been published in peer-reviewed journals because the patients are still young and the trial is ongoing. When the Advisory Committee on Heritable Disorders in Newborns and Children, convened by HHS, met in February—before the promising data were released—five of 13 voting members opposed routine SMA screening.

“It concerns me about not having published, peer-reviewed literature,” said one, Joan Scott, who directs services for children with special health needs at the Health Resources and Services Administration in Rockville, Maryland. Scott Shone, a senior public health analyst at RTI International in Research Triangle Park, North Carolina, added, “If all this robust data exists, why was it not presented?” He noted that no one knows whether the drug will continue to help kids as they age. “There’s a huge unknown there,” Shone said.

There simply hasn’t been time to accumulate long-term data, says Wildon Farwell, senior medical director in clinical development at Biogen. But, he says, “All the data we see shows that treating patients before symptom onset allows the potential for greater benefit than waiting until symptoms occur.”

A theoretical model developed for the advisory committee by outside experts estimated that screening would spot about 150 babies each year who otherwise would not be identified until symptoms set in; diagnosis can take months after that. Those months may be crucial: One study showed that in the sickest patients, 90% of motor neurons are destroyed by the age of 6 months.

https://bit.ly/2Kyf0Bb

Major donor nixes effort to combat tuberculosis crisis in North Korea

A fuse is about to be lit on an infectious disease powderkeg in northeast Asia. On 30 June, The Global Fund to Fight AIDS, Tuberculosis and Malaria will pull the plug on its grants to North Korea, which has one of the highest rates of tuberculosis (TB) in the world. The pullout leaves the isolated nation with about 1 year to line up a new source of medicines and diagnostics to combat a deepening TB crisis.

The Global Fund’s decision to sever ties to North Korea perplexes some humanitarian workers and medical researchers who operate there. “We have not gotten any clarity on why they are doing this,” says Kwonjune Seung, a physician at Brigham and Women’s Hospital in Boston and medical director of the Eugene Bell Foundation, a nonprofit in Andrews, South Carolina, that has supported TB clinics in North Korea since 2007. “I would hope it was something extremely egregious,” for the Global Fund “to take such a drastic step.” Some, however, see the move as a negotiating ploy and predict that the organization will be back in North Korea before TB supplies run out.

Since 2010, the Global Fund, a public-private partnership based in Geneva, Switzerland, has spent more than $100 million on TB and malaria control in North Korea through grants managed by two international organizations with offices in Pyongyang—the World Health Organization (WHO) and UNICEF—as well as North Korea’s Ministry of Public Health (MPH). “It has been the biggest outside investment ever in public health in North Korea,” says Kee Park, a neurosurgeon at Harvard Medical School in Boston who leads biannual exchanges with North Korean health care specialists.

By all accounts, malaria control efforts in North Korea have been a clear success. Cases have fallen from 13,500 in 2010 to 2719 in 2016. The Global Fund has provided enough mosquito nets and antimalarial drugs to see the country through the 2018 malaria season, says spokesperson Seth Faison, who is based in Geneva.

But TB remains a stubborn and worsening problem. A quarter-century ago, North Korea’s TB prevalence—around 50 cases per 100,000 people—was approximately one-third of South Korea’s. But after a severe, prolonged famine in the North in the mid-1990s, the TB bacterium spread rapidly among malnourished survivors. According to WHO, North Korea’s TB incidence, or number of new cases, per 100,000 people shot up from under 200 in 2000 to 513 in 2016 (global incidence in 2016 was 140). An MPH survey carried out in 2015 and 2016—which outside experts laud for its rigor—pegged North Korea’s TB prevalence, or total cases, at 640 per 100,000 people.

Most North Korean TB patients now under medical care are taking drugs purchased under Global Fund grants. The Eugene Bell Foundation is providing drugs to treat about 1200 North Koreans with multidrug resistant (MDR) TB each year. That represents about 10% to 15% of each year’s new MDR cases, Seung says. MPH had proposed carrying out a drug-resistance survey in the next tranche of money from the Global Fund, he says, but that won’t happen now.

In announcing its decision last February to end grants to the Democratic People’s Republic of Korea (DPRK)the Global Fund cited its concern that the country’s “unique operating environment” prevented the group from providing “the required level of assurance and risk management” for its grants. Humanitarian groups and medical researchers criticized the decision in letters to The Lancet and in other forums. They implored the Global Fund to reconsider, noting that transparency concerns and challenging operating environments exist in many countries with high TB burdens. The Global Fund “has not modified its decision” to close the grants, Faison says. However, he says, “We hope to re-engage with DPRK when the operating environment allows the access and oversight required.”

Still, “the public outcry did have an effect,” Park says. The Global Fund recently agreed to allow leftover funds from its North Korea grants to be spent on a buffer stock of medications and diagnostics “sufficient to provide for continued treatment for TB patients [through] June 2019,” Faison says. There appear to be enough drugs on hand not only to treat existing patients, but also to enroll new patients through December, Park says. “The hope is that will buy enough time” to find a successor to the Global Fund, says Heidi Linton, executive director of Christian Friends of Korea, a nonprofit in Black Mountain, North Carolina, that a few years ago helped establish a National Tuberculosis Reference Laboratory in Pyongyang.

That won’t be easy, Seung says. “TB is a tough sell. It’s complex and messy, and makes donors tired.” He and observers hope the South Korean government will step in, if only to prevent TB—especially MDR strains—from spilling across the border.

One observer—a humanitarian worker who has discussed the issue privately with Global Fund officials—suggests the fund’s pullout is tactical. Closing the grants, he says, may give the fund leverage to negotiate access to more clinics in North Korea where TB drugs are dispensed, and on shorter notice. The expiring grants stipulate access to 70% of clinics on 4 days’ notice; the Global Fund, he says, has been pushing for access to all clinics on as short as 1 day’s notice.

In the meantime, humanitarian groups are bracing for tough times as international sanctions take an increasing toll. Many North Koreans “are struggling to make ends meet,” says Linton, who spends several weeks a year on the ground there. Malnutrition and a lack of access to clean water in many villages continue to make people vulnerable to TB, she says. The areas of North Korea that are most affected by TB “are disproportionately those without electricity, without access to health care, and most in need of assistance,” says Taehoon Kim, co-founder of DoDaum, a nonprofit in New York City with health programs in North Korea. North Korea’s public health system “will be tested more and more in the coming years,” he says. In the wake of the Global Fund’s pullout, Kim says, “I’m gravely concerned about whether it will be able to respond.”

https://bit.ly/2KyiZ4e

Migraines Strain Family Ties

Migraine headaches can have a variety of detrimental effects on family life, researchers reported here.

Results from the CaMEO study showed that having chronic migraine influences decisions about when to get married and whether to have children. Another study found that a parents migraines have an impact on children’s well-being and parent-child relationships.

The studies were presented at the American Headache Society (AHS) annual meeting.

“Both studies illustrate the fact that migraine is a pervasive disease — it doesn’t just affect the person suffering from migraine, but also their families. I think it also illustrates a bigger societal problem that we have about stigma and the need to educate the general public about what migraine is and the impact it has on so many people,” AHS session moderator Rashmi Halker, MD, of the Mayo Clinic in Phoenix told MedPage Today.

CaMEO Findings

Dawn Buse, PhD, of Albert Einstein College of Medicine in New York City presented results from a substudy of CaMEO (Chronic Migraine Epidemiology and Outcomes), an ongoing longitudinal web-based survey that has collected data on symptoms, treatment, and quality of life from thousands of people with migraines in the U.S.

“We all work with patients with migraines and we know what a big impact this can have on so many important areas of their lives, but we wanted to quantify it in a systematic way,” Buse said.

Of the nearly 20,000 migraine patients who met the study criteria and were invited to complete the Family Burden Module (FBM) of the survey, a total of 13,064 were included in the sample: 11,938 with episodic migraines and 1,126 with chronic migraine.

Participants were classified according to whether they were not currently in a relationship, in a relationship but not living together, or in a relationship and living with their partner. They were asked how headaches affected their current or past relationships. Those with children living at home were asked how headaches affect their parenting and other aspects of family life.

Of the 3,512 respondents not in a current relationship, 16.8% said their headaches had been a problem in previous relationships, including contributing to a relationship ending. This was the case for 37.0% of people with chronic migraine and 15.0% of those with episodic migraines. Results were similar for men and women.

Among the 1,395 people who were in a relationship but not living together, 17.8% said their headaches had caused problems, including preventing them from developing a closer relationship such as moving in together or getting married. Again, this was more likely for people with chronic migraine (43.9%) than for those with episodic migraines (15.8%).

Among the 8,157 respondents in a current live-in relationship, 49.0% said they thought they would be a better partner if they did not have headaches; 78.2% of those with chronic migraine and 46.2% of those with episodic headaches thought this would be the case.

“On perhaps the most heartbreaking question, 10% of people with chronic migraine had made different choices about having children because of their headaches,” Buse reported.

On this subject, 9.6% of chronic migraineurs and 2.6% of those with episodic migraines said they had delayed having children or had fewer children due to their headaches. Among those who did have kids, 64.8% and 35.7%, respectively, said they would be a better parent if they did not have migraines. Respondents said their headaches interfered with things like participating in social events with their children or helping them with homework.

Buse recommended that providers should consider the overall burden of disease when managing patients with migraine, especially those with chronic headaches. She suggested that personalized treatment plans could include behavioral interventions for the patient, the couple, and other family members as appropriate.

Impact on Kids

Elizabeth Seng, PhD, also of Albert Einstein College of Medicine, presented findings from a study of the impact of a parent’s migraine on their children.

This analysis included 40 pairs consisting of a parent who experienced migraine and a child, ages 11-17 years, living at home. The families were predominantly white, well-educated, and relatively affluent. Parents and children were required to have separate email addresses and the parents were encouraged to let their children complete the survey without interference.

All but one of the parents were mothers and most were married. They had a median of 6.8 headaches per month, with an average severity of 6.8, and two-thirds reported severe disability on the MIDAS (Migraine Disability Assessment) questionnaire. The children had an average age of 13.6 years and boys and girls were about equally represented; 60% of the children reported having headache attacks themselves.

Parents and children both reported that the parents’ migraine had a moderate impact, with the strongest effects seen on the child’s overall well-being and parent-child relationships, followed by the burden of providing daily help and emotional impact. More than 60% of the children said they would like more training to teach them how to better care for their parent with migraine.

However, in some cases the parent-child pairs did not show much agreement, Seng noted. Although a majority of the parents thought their children could benefit from support groups or speaking with someone in a similar situation, only a quarter of the children agreed. Likewise, only 27% of the children though it would be helpful to speak with a professional counselor. “The kids said ‘This doesn’t sound so great,'” Seng reported.

“Half of the children also had migraine, and that was not something we selected for,” Send told MedPage Today. “There are lifestyle factors that are important for managing migraine, like managing stress, getting to sleep at the same time every night, not skipping meals. These are healthy for all of us, but are particularly important for people with migraine. If we can get families to decide that ‘We’re gong to eat small healthy meals together, that we’re going to go to bed at the same time,’ that’s only going to help everyone’s health.”

The CaMEO study was sponsored by Allergan.

Buse disclosed support from and relevant relationships with Allergan, Avanir, Eli Lilly, and Promius.

Seng disclosed relevant relationships with GlaxoSmithKline and Eli Lilly.

• Primary Source

  American Headache Society

  Source Reference: Buse D et al “Life with migraine, effect on relationships: Results of the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study” AHS 2018; Abstract OR-06.

• Secondary Source

  American Headache Society

  Source Reference: Seng E et al “When mom has migraine: An observational study of the burden of parental migraine on children.” AHS 2018; Abstract OR-07.

https://bit.ly/2lOgjBb