Sanofi and Regeneron partner to develop new antibody cancer treatments

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Sanofi has partnered with Regeneron Pharmaceuticals to discover, develop and commercialise new antibody cancer treatments in the field of immuno-oncology.

Under the deal, both firms will jointly develop a programmed cell death protein 1 (PD-1) inhibitor that is currently in Phase I testing and intends to start clinical trials in 2016 with new therapeutic candidates based on ongoing and innovative preclinical programmes.

The new deal will cover both monoclonal antibodies and new bi-specific antibodies. Regeneron will take the responsibility for discovery, antibody generation and development through proof-of-concept (PoC), while Sanofi will take care of further development and commercialisation.

With an ability to extend the collaboration for selected ongoing programmes for an additional three years, the exclusive collaboration to discover and develop potential monotherapy or novel combination immuno-oncology antibody candidates through PoC will be for five years.

Regeneron chief scientific officer and Regeneron Laboratories president Dr George Yancopoulos said: “The efficiency and power of our suite of technologies, such as VelocImmune and VelociGene, combined with our human genetics capabilities, uniquely positions the alliance to accelerate the development of potential new immuno-oncology treatment options for cancer patients.”

As part of the deal, Regeneron will receive an upfront payment of around $640m from Sanofi and the firms will invest $1bn in discovery through PoC development (Phase II a study) of monotherapy and novel combinations of immuno-oncology antibody candidates to be funded 25% by Regeneron ($250m) and 75% by Sanofi ($750m).

The firms have also agreed to equally invest an additional $650m to develop PD-1 inhibitor REGN2810.

Regeneron will also receive a one-time milestone of $375m from Sanofi in the event that sales of a PD-1 product and any other collaboration antibody sold for use in combination with a PD-1 product exceed, in the aggregate, $2bn in any consecutive 12-month period.

The firms also have agreed to re-allocate $75m over three years for immuno-oncology antibodies from Sanofi’s $160m annual contribution to their existing antibody collaboration, which was announced in November 2009.


Novartis and Genmab seek FDA approval for ofatumumab to treat relapsed CLL

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Novartis and Genmab are seeking approval from the US Food and Drug Administration (FDA) for their ofatumumab (Arzerra) as maintenance therapy for patients with relapsed chronic lymphocytic leukaemia (CLL).

Ofatumumab is a human monoclonal antibody, which is developed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.

Under Genmab’s ofatumumab collaboration, Novartis has submitted a supplemental biologics licence application (sBLA) to the FDA for the uses of ofatumumab as maintenance therapy of patients with CLL.

The sBLA was submitted based on interim results from a Phase III study, Prolong (OMB112517), which assessed ofatumumab maintenance therapy against no further treatment in patients with a complete or partial response after second or third line treatment for CLL.

Genmab CEO Dr Jan van de Winkel said: “The submission of the application to expand the label to use ofatumumab as a maintenance therapy for patients with relapsed CLL in the US follows closely behind the marketing application for this indication in Europe.

“We are looking forward to the response from both the US and European regulatory authorities, and hope that ofatumumab will soon become available for maintenance therapy of patients with relapsed CLL.”

In the US, Arzerra received approval for use in combination with chlorambucil to treat previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate.

In the EU, Arzerra obtained approval for use in combination with chlorambucil or bendamustine to treat patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy.

Arzerra is also indicated as monotherapy to treat patients with CLL who are refractory after prior treatment with fludarabine and alemtuzumab, in around 50 countries worldwide.

Under the co-development and collaboration agreement, Genmab and Novartis, as successor in interest to GSK, markets Arzerra in different countries.


Recently-developed drug holds great promise for children with acute lymphoblastic leukaemia

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A new Australian study shows that a recently-developed drug, already used safely in adult leukaemia clinical trials, holds great promise for some children with an aggressive form of cancer known as acute lymphoblastic leukaemia (ALL).

Each year, around 150 Australian children and almost as many adults are diagnosed with ALL, which is the most common childhood cancer. Around 15% will have an aggressive subtype of ALL (known as T-ALL) that is generally less responsive to therapy and more likely to relapse.

Professor Richard Lock and Dr Donya Moradi Manesh from Children’s Cancer Institute have shown that a drug known as PR-104 is effective against laboratory models of aggressive T-ALL.

Their findings are now published online in the prestigious journal Blood.

The research team tested PR-104 through the Pediatric Preclinical Testing Program, a consortium funded by the US National Cancer Institute (NCI) to prioritise and fast track new drugs into clinical trials in children with aggressive cancers. Children’s Cancer Institute is the only testing site located outside of the US, and conducts all of the consortium testing against childhood ALL.

“During the 10 years we’ve been funded under the NCI program, we’ve tested over 70 drugs and combinations, and PR-104 is one of the most exciting yet – with the potential to be fast-tracked into clinical trials for children,” said Professor Richard Lock.

“We were so encouraged by our first results with PR-104 that we undertook additional studies which showed the drug to be preferentially active against T-ALL, a subtype of ALL affecting white blood cells known as ‘T cells’.

“Around 15% of acute lymphoblastic leukaemia patients have T-ALL, while 85% have a disease that affects their ‘B cells’, another white blood cell type. PR-104 is much less effective against these B cell leukaemias.

“We believe that PR-104 might be an effective drug for patients who have initially benefited from conventional treatment for T-ALL, but who have subsequently relapsed.”

At first baffled by why T-ALL responded to PR-104, the researchers realised that only the T cell subtype expressed high levels of AKR1C3, an enzyme that activates PR-104.

The research team is in the process of examining the molecular biology behind AKR1C3, and trying to understand why T-ALL cells express very high levels of the enzyme.

“If we can work out what activates this enzyme in T cells, we might find a way of activating it in B cells, making the B cell disease sensitive to the drug as well,” said Professor Lock.

“Obviously it would be ideal if we could extend this drug’s reach to include all acute lymphoblastic leukaemia patients.

“In the meantime, we can envisage using PR-104 to target highly aggressive T-ALLs that express high levels of AKR1C3.

“We are actively pursuing opportunities to conduct a clinical trial to treat childhood T-ALL with PR-104.”


Children’s Cancer Institute Australia

‘Game changing’ new lung cancer drug is available from today

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Vaccine trains the body to single out diseased cells that experts say will double survival rates

Lung cancer patients are to be offered a ‘game-changing’ treatment that trains the body to single out and attack diseased cells. It is being made available under a Government policy that enables life-saving treatments to be fast-tracked through the licensing process that usually takes years. Administered in a vaccine every two weeks, the drug nivolumab works by teaching the body’s immune system to attack cancerous cells.

Evidence shows the effect continues for several years after the treatment has stopped. Experts have hailed such immunotherapy as a ‘new era’ in the fight against cancer. Early trials have suggested it doubles survival rates. From today, doctors will be able to offer nivolumab free to patients with advanced lung cancer, for whom surgery is no longer an option. The costs will be footed by the manufacturer, Bristol-Myers Squibb. The therapy differs from ‘blanket’ treatments such as chemotherapy and radiotherapy which kill all cells including healthy ones.

This means there are fewer debilitating side effects such as fatigue, sickness, hair loss and infections caused by healthy cells being destroyed. Some skin cancer patients previously diagnosed as terminal have been able to return to work following immunotherapy. They only need to top up jabs every few months. Lung cancer is one of the deadliest forms of the illness. Only 5 per cent of patients are still alive ten years after diagnosis. It is also the second most common – after breast in women and prostate in men – with 43,000 new cases each year. Nivolumab is the third treatment made available through the Early Access To Medicines Scheme which bypasses red tape that can last up to a decade. Manufacturers submit data on new drugs to experts at the Medicines and Healthcare Products Regulatory Agency for assessment.

If the watchdog is satisfied the treatment can be beneficial without causing harm, it is made available to patients. Costs are covered by the manufacturer until the drug is formally licensed in the usual way. The scheme means patients are effectively guinea pigs testing out new drugs and possible side effects, but the Government hopes it will save hundreds of lives. George Freeman, Life Sciences Minister, said: ‘The positive scientific opinion of nivolumab offers real hope to those who need it most… I hope this is just one of many drugs that will be made available.’

A trial involving 272 patients found 42 per cent taking nivolumab were alive a year later, compared with just 24 per cent who had chemotherapy. Some of those on the drug are still living two years on. Dr Tom Newsom-Davis, consultant cancer specialist at Chelsea and Westminster Hospital, said: ‘Lung cancer is one of the most difficult to treat … early access to nivolumab is therefore very positive … patients have the potential to access a new medicine which has shown in clinical studies to offer significant extension of survival.’ Manufacturers say 10,000 UK patients could benefit from the jab. Last month experts said immunotherapy was a ‘game-changer’ and the biggest breakthrough since chemotherapy.

By Sophie Borland Health Correspondent

FDA provides safety update about Essure Birth Control Implant

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The FDA first announced their intention to provide a safety update about Essure late yesterday evening. Today’s much anticipated report comes on the heals of a private citizen petition that raised serious concerns about the Essure Birth Control Implant and resulted in the launch of an FDA investigation into the birth control device.

This afternoon the U.S. Food and Drug Administration (FDA) added a page to their website informing the public of increased risks associated with the Essure Permanent Birth Control Implant. The new page acknowledges the 5,093 adverse events that have been reported to the agency about Essure and provides new information about serious risks associated with the device including: pelvic pain, migration of Essure coils, perforation of the uterus or fallopian tubes, and rash and itching. The page also advises physicians to warn patients about complications that have resulted in women with nickel allergies who have received the Essure Birth Control Implant.

One section of the webpage recognizes reports of miscarriage and ectopic pregnancy following the non-surgical sterilization procedure, stating, “The FDA will continue to monitor the safety of Essure to make certain that its benefits of providing women with a non-incisional sterilization choice continue to outweigh its risks,” and “While scientific evidence shows that Essure is a highly effective means of sterilization when health care providers and patients follow the appropriate instructions for use, no form of birth control is 100% effective.”

The FDA announced today that there will be a public meeting of their Obstetrics and Gynecology Devices Panel later this year on September 24, 2015, to discuss the safety and efficacy of the device.

Source: Arentz Law Group

China rejects patent linked to Gilead hepatitis C drug

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China has rejected a Gilead Sciences Inc patent application related to its costly hepatitis C drug, a U.S. advocacy group said, adding the move may lead to other countries to consider rejecting patents for the controversial treatment.

Gilead has drawn fire for the cost of its top-selling drug Sovaldi, priced at $1,000 per pill in the United States or $84,000 for a typical 12-week course and its patents have been challenged in the U.S., India and Europe.

The application China has rejected was for a so-called prodrug, the inactive form of the drug which then converts into the chemically active compound once in the body, the New York-based Initiative for Medicines, Access & Knowledge (I-MAK) said.

Gilead, however, holds the China patent to the base compound in the drug, also known by its generic name sofosbuvir and China’s rejection of the prodrug patent does not open the way for copycat drugs to be made in the world’s No. 2 drug market.

China-based officials for Gilead were not immediately available for comment. Emails and calls to Gilead’s U.S. offices outside office hours went unanswered.

Officials at China’s State Intellectual Property Office did not confirm the decision when contacted by Reuters, but a notice posted on the body’s website said Gilead’s application for “nucleoside phosphramidates”, a kind of prodrug, had recently been rejected.

China’s move follows a decision by India’s patent office in January to reject Gilead’s patent application for Sovaldi, finding it was not inventive enough. Gilead is appealing the ruling.

Under pressure to cut prices, the California-based firm agreed last year to make the drug available for lower prices in 91 developing countries.

I-MAK has brought legal challenges against Gilead’s patents or patent applications in five countries not covered by the agreement: China, Argentina, Brazil, Russia and Ukraine.

Charities in Europe have also challenged Gilead’s patent over its prices.

The World Health Organization says as many as 150 million people worldwide live with chronic hepatitis C infection, most of them in low and middle-income countries. It recently added Sovaldi to its essential medicines list and urged lower prices, especially in middle income countries.

By Brendan Pierson and Adam Jourdan, Reuters

(Editing by David Gregorio and Edwina Gibbs), Reuters

Merck seeks FDA approval for grazoprevir / elbasvir to treat HCV GT1, 4 or 6

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Merck is seeking approval from the US Food and Drug Administration (FDA) for its grazoprevir / elbasvir (100mg/50mg), an investigational once-daily, single tablet combination therapy to treat adult patients with chronic hepatitis C genotypes (GT) 1, 4 or 6 infection.

The company has submitted a new drug application (NDA) to the FDA for the drug and is planning to submit additional licence applications in the European Union and other markets by the end of this year.

Grazoprevir / elbasvir is an investigational and once-daily single tablet regimen that includes grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor).

Under the firm’s broad clinical trials programme, grazoprevir / elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV / HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and liver cirrhosis, as well as those on opiate substitution therapy.

Merck Research Laboratories clinical development senior vice-president Dr Roy Baynes said: “Merck’s submission is based on evidence from our wide-ranging clinical programme assessing the efficacy and tolerability profile of grazoprevir/elbasvir in populations with chronic hepatitis C.

“This submission to the US FDA is an important milestone as we seek to provide patients with a new treatment option for this serious infection.”

The NDA was submitted based on data from the pivotal C-EDGE clinical trials programme and C-Surfer and C-Salvage trials, which assessed grazoprevir / elbasvir (100mg / 50mg), with or without ribavirin, in patients with chronic hepatitis C infection.

Earlier, the firm received FDA breakthrough therapy designation for grazoprevir/elbasvir to treat patients infected with chronic HCV GT1 with end stage renal disease on haemodialysis, and for patients infected with chronic HCV GT4.

Source: (Kable, a trading division of Kable Intelligence Limited.)

More Mandates for FDA

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New proposals from Congress to spur innovation will strain resources needed for regulatory approval.

With a bipartisan “21st Century Cures” bill moving through Congress, and negotiations beginning on how the next round of user fees will shape FDA policies and priorities (see sidebar), there’s great optimism in Washington that these efforts will yield real improvements in biomedical discovery and drug development to speed new therapies to patients. FDA officials, though, are nervous about finding resources to implement new mandates while maintaining an efficient review process.

Despite broad support for the “Cures” bill negotiated by leaders of the House Energy & Commerce (E&C) Committee, there may be a long wait for Senate action. E&C chairman Fred Upton (R-Mich) is looking for final House approval this summer, but members of the Senate Health, Education, Labor and Pensions (HELP) Committee are crafting their own innovation legislation and don’t expect a bill until fall.

The House measure gained Democratic support by offering a hefty budget increase for the National Institutes of Health (NIH) and under pressure, agreed later to add a sizeable funding increase for FDA. The measure proposes to boost NIH funding by $5 billion over three years (to hit $35 billion in 2018) and provides another $10 billion over five years to support a new NIH Innovation Fund.

FDA is authorized less than $100 million a year to support clinical trial modernization and evidence development. More important, added language exempts FDA user fees from budget sequestration and proposes “pay for” options. But despite a groundswell in support for greater government funding for biomedical research, there’s no indication that Congressional appropriators will provide any new money for NIH or FDA.

Meanwhile, Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), fears that a law requiring new programs and multiple guidances will undermine her ability to meet review and approval commitments. This latest E&C proposal has “significant resource implications for FDA,” Woodcock stated at an April E&C health subcommittee hearing. CDER’s new drug review process is now “going at full speed, and we’d like to keep it that way,” she commented, warning that timely sponsor meetings important for accelerating innovative development programs “would be the first to go” if the agency gets further stretched on resources.

FDA’s first priority is to implement statutory requirements set by Congress, she explained. Next comes meeting user fee goals negotiated with industry. The extensive resources needed to advise on clinical programs and to collaborate on biomarkers might have to be scaled back.

Help on hiring

What FDA sorely needs, says Woodcock and others, is to cut some of the red tape and obstacles to recruiting and retaining experts able to address complex scientific and regulatory issues. Too-low salaries prompt experienced staffers to leave for more rewarding jobs in industry and academia, and complex government employment practices make it hard to attract top talent. Woodcock told the Senate HELP Committee that staff turnover “is a huge problem for us” and that FDA has “a desperate time” bringing in neurologists due to low salaries.

Jeffrey Shuren, director of the Center for Devices and Radiological Health (CDRH), similarly described FDA as the “training ground for industry,” as young professionals leave after a few years for industry jobs offering salaries two or three times what they make at FDA, and where the work load is more manageable. When medical reviewers depart right in the middle of processing an application, Shuren added, that ultimately hurts patients as well as regulated companies.

The “Cures” legislation would help FDA by raising some pay rates and making it slightly easier to employ certain specialists. Woodcock also would like new hires from biopharma companies to be able to place securities in blind trusts instead of having to sell them to come to FDA. And she sought more “direct hire authority” to speed up the employment process for certain health professionals able to “go toe-to-toe with industry scientists.”

Seeking agreement

To gain Democratic support for the Cures initiative, Republicans agreed to the NIH budget increase and dropped some controversial provisions, such as extended exclusivity on certain new medical products. But there is agreement to reauthorize the priority review voucher program for rare pediatric diseases, which is set to expire, as well as an initiative to spur development of new antibiotics, utilizing a modified approval pathway for therapies targeted to limited populations. The legislation encourages more sharing of research and clinical data by removing barriers to national interoperability of e-health records. And there’s support for telemedicine, for faster coverage decisions on new vaccines, and for a breakthrough program for medical devices.

Under the heading of achieving a “faster, safer and more personalized” research system, the “Cures” bill backs greater use of central, or “lead,” institutional review boards (IRBs) to oversee multi-site studies, authorizes greater use of “clinical experience” reports to help support FDA approval of certain new indications, and gives FDA flexibility to approve “qualified indications” based on clinical data summaries, as opposed to full case reports.

Payers as well as pharma companies support flexibility in presenting healthcare economic information to formulary committees and insurers, a change likely to increase industry investment in economic analysis, according to a report by Avalere Health. And a “medical education” provision would revise the “Sunshine” disclosure program to make it easier for marketers to distribute journal articles and medical textbooks to physicians and to support certain continuing medical education events.

Even though FDA already is doing much to accelerate biomarker qualification, the process could benefit from Congressional backing, says former FDA commissioner Andrew von Eschenbach. He emphasized at a recent Alliance for Health Reform briefing that biomarker assessment is key to furthering precision medicine and predicted that Congress will pass “transformational legislation” this year; just how big the bill will be, he added, is “a work in progress.”

By Jill Wechsler,

Cabazitaxel – carboplatin combination chemotherapy holds promise as treatment for advanced prostate cancer

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For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel.

For example, docetaxel is commonly used as the “first-line” therapy, while cabazitaxel is used as the “second-line” therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied.  However, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Centre may change the perspective on a role for combination chemotherapy in advanced disease.

The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin – a type of platinum chemotherapy – in patients with mCRPC. To date, 160 men have been randomised to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.

To monitor the effects of treatment, MD Anderson researchers tracked several variables including Progression Free Survival (PFS), as well as changes in blood levels of prostate-specific antigen (PSA) and bone-specific alkaline phosphatase (BAP, a marker of prostate cancer in bone cells). In addition, safety and toxicity were monitored for both patient groups.

Cabazitaxel – carboplatin combo demonstrated significantly longer Progression Free Survival versus single agent chemotherapy

Analysis and comparison of the data demonstrated that median PFS was significantly longer for patients receiving combination versus single agent chemotherapy (6.7 months vs 4.4 months, respectively). Furthermore, reductions in both PSA and BAP were greater for the combination therapy group. PSA reductions greater than 50% occurred 60% of the time with combined chemotherapy vs. 44% with the single drug. PSA reductions greater than 90% occurred 28% of the time with two chemotherapy drugs vs. 20% with one. In addition, BAP reductions greater than 50% for combination vs. single drug were 63% and 25% respectively.

Side effects, such as fatigue, anemia and neutropenia were comparable for both the single-drug regimen and two-drug regimen. In addition, there were no significant toxicity events.

“We believe cabazitaxel – carboplatin combination chemotherapy may become the clinical standard for advanced prostate cancer once additional safety, efficacy and overall survival data is generated,” explained Paul Corn, M.D., Ph.D., an associate professor of genitourinary medical oncology at MD Anderson. “Dr Ana Aparicio’s lab is currently developing tumour-specific biomarkers to identity patients with an aggressive variant of prostate cancer most likely to benefit from this approach.”

The study was funded by Sanofi.

By Victoria White,

Type 2 diabetes drugs linked to deadly ketoacidosis

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A new class of drugs, SGLT2 inhibitors, used to treat type 2 diabetes have been linked to diabetic ketoacidosis which can be deadly if left untreated.

A certain class of type 2 diabetes drugs can lead to a life-threatening condition called ketoacidosis, the U.S. Food and Drug Administration warns.

These prescription drugs are called sodium-glucose cotransporter-2 (SGLT2) inhibitors and include canagliflozin, dapagliflozin and empagliflozin. They work by prompting the kidneys to remove sugar in the blood through urine.

The drugs are sold under the brand names:Invokana (canagliflozin), Invokamet (canagliflozin and metformin), Farxiga (dapagliflozin), Xigduo XR (dapagliflozin and metformin extended-release), Jardiance (empagliflozin), Glyxambi (empagliflozin and linagliptin).

Between March 2013 and June 2014, the FDA received 20 reports of the drugs triggering ketoacidosis, in which levels of blood acids called ketones are too high. If untreated, ketoacidosis can lead to a diabetic coma or even death, according to the American Diabetes Association.

All 20 patients had to go to an emergency department or were hospitalised, the FDA said.

Ketoacidosis typically affects people with type 1 diabetes, but all of these cases involved people with type 2 diabetes and the condition manifested itself slightly differently than in people with type 1 diabetes, the FDA said in a news release.

The agency said it’s investigating the issue to see if changes are needed in the prescribing information for . The drugs are approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes.

Patients taking SGLT2 inhibitors should monitor themselves for any signs of ketoacidosis and seek immediate medical attention if they develop symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness, the FDA said.

Testing for ketones

Ketones can be detected with a simple urine test using a test strip, similar to a blood testing strip, and you should ask your health care provider about when and how to test for ketones, according to the diabetes association.

Patients shouldn’t stop or change their diabetes medications without first talking with their doctor. If ketoacidosis is confirmed in a patient, doctors should take the patient off SGLT2 inhibitor, take appropriate action to correct the condition and monitor sugar levels, the FDA advised.

Taken from Health24 / HealthDay