On February 19, 2016 Oncology Venture Sweden AB (OV:ST) reported that it has in-licensed LiPlaCis from LiPlasome Pharma ApS, Denmark (Press release, Oncology Venture, FEB 19, 2016, View Source;as-third-drug-in-ov-pipeline,c9919954 [SID1234532173]). LiPlaCis is the third drug in OV’s pipeline and will be the first prospective trial using the Drug Response Predictor – DRP. LiPlaCis is the lead product in LiPlasome Pharma – mainly owned by Vecata Invest A/S an investment company managing the Bagger-Sorensen Group’s investments in the venture segment. LiPlaCis – a liposomal formulation of cisplatin – is just finalizing the dose escalation part of a phase 1 study in solid tumors and is on the verge of moving into the extension phase where screened breast cancer patients with metastatic disease will be treated. Using analysis of patients own biopsies by the DRP patients are screened beforehand for high likelihood of effect of the LiPlaCis drug. The DRP should thereby enable a high response rate and give breast cancer patients a new effective treatment opportunity. There is no sign on fee and no up-front payment to LiPlasome. The License agreement is based on a revenue split between the parties once the LiPlaCis product is commercialized. It is anticipated that more capital will be needed to take LiPlaCis the whole way to outlicensing/exit. OV will raise money when it is needed and as previously announced each product including LiPlaCis is budgeted to cost approximately 2 mUSD on average.

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"This is a key step for OV – the team in OV has the last three years worked with MPI and LiPlasome on LiPlaCis and the fact that OV can now take over the responsibility for this promising project is indeed a major step forward for OV", Said Adjunct professor Peter Buhl Jensen, MD, PhD and CEO of Oncology Venture. "We know the project well and we are proud that Vecata Invest as the major owner has let us include LiPlaCis in the OV portfolio. We trust we can develop LiPlaCis into a new effective treatment opportunity for breast cancer patients", Dr. Buhl Jensen further commented."

"We are very happy to out-license the lead product LiPlaCis to Oncology Venture which we believe is a better home for a product progressing into a more advanced level in clinical development", Said Hans-Henrik Eriksen CEO of Vecata Invest. "Oncology Venture has a proven team and in our joined advisory board we look forward to a continued collaboration bringing LiPlaCis to cancer patients."

LiPlaCis is a liposomal formulation of cisplatin. LiPlaCis is finalizing a promising clinical phase 1-studie with early responses in non-screened patients with solid tumors (one patient with esophageal cancer and one patient with skin cancer) and is on the verge of entering an extension phase 2 design study in which 12 breast cancer patients will be treated based on screening using the DRP and where efficacy will be measured. LiPlaCis is thereby the most advanced drug in the Oncology Venture pipeline. The team responsible for running the phase 1 trial is the OV team which is an advantage as OV is therefore very familiar with the product manufacturing, regulatory communication as well as the conduct of the study at the clinical site. Thus, there will be no time wasted in the takeover period.

In a collaboration with the Danish Breast Cancer Cooperative Group (DBCG) including nine Danish breast cancer sites more than 900 patients with metastatic breast cancer have participated in the screening for high likelihood responders to LiPlaCis. Biopsies from the patients have been analyzed by the LiPlaCis DRP and the project is very soon to start include patients. The LiPlaCis active ingredient is cisplatin and the Cisplatin DRP has been previously validated retrospectively in a lung cancer study and now also in a prospective lung cancer study (Abstract submitted to ASCO (Free ASCO Whitepaper)). OV therefore prioritize this proof of concept study with LiPlaCis in breast cancer patients. This is the fastest possible first prospective trial using the DRP method.

The LiPlaCis deal
There is no sign on fee and no up-front payment to LiPlasome. The License agreement is based on a revenue split between the parties once the LiPlaCis product is commercialized. It is anticipated that more capital will be needed to take LiPlaCis the whole way to outlicensing/exit. OV will raise money when it is needed and as previously announced each product including LiPlaCis is budgeted to cost approximately 2 mUSD on average.

About LiPlaCis
Cisplatin is one of the most widely used drugs in the treatment of cancer due to its documented efficacy in a number of tumour types. Cisplatin is used in the treatment of large indications as lung cancer EU+US ≈ 480,000 new cases annually), head and neck cancer (500,000 cases annually worldwide) bladder cancer (EU+US ≈ 170,000 annually) and ovarian cancer (EU+US ≈ 71,000 annually). The lipid formulation from LiPlasome is the answer to a well-established need for improving cisplatin therapy and improving the formulation of the drug, so that a more selective up-take of cisplatin administered takes place at the tumour sites. LiPlasome Pharma ApS has identified and incorporated a mechanism into their liposomes – called LiPlasomes – designed to trigger the release of an encapsulated drug specifically in the tumour tissue. An enzyme especially present on tumors called secretory phospholipase A2 (sPLA2), is utilised to break down the LiPlaCis once it has accumulated in the cancer tissue. The lipid composition of the LiPlasomes is tailored to be specifically sensitive to degradation by the sPLA2 enzyme and thereby for release of the encapsulated drug. The technology behind LiPlaCis was originally developed by scientists from Danish Technical University -DTU.

More about LiPlaCis and the clinical testing
The Phase 1 study to evaluate the safety and tolerability of LiPlaCis in patients with advanced tumours is running at a Phase 1 Unit at a University Hospital in Copenhagen and has included 18 patients in the dose escalation part of a phase 1 study in solid tumors. The LiPlaCis program is now on the verge of moving into the extension phase 2 designed trial (part of the phase 1 application where patients with a specific disease – here metastatic breast cancer – are included to investigate early Proof of Concept – i.e. effect of the drug. LiPlaCis is administered intravenously in cycles weekly on day 1, day 8 Upon the investigator’s judgement the patient may continue treatment for more than 3 cycles when benefiting from the study drug.

About the Drug Response Predictor -DRP – screening tool
Oncology Venture uses the MPI DRP to select those patients that by the gene signature in their cancer is found to have a high likelihood of response to the drug. The goal is to develop the drug for the right patients and by screening patients before treatment the response rate can be significantly increased.

This DRP method builds on the comparison of sensitive vs. resistant human cancer cell lines including genomic information from cell lines combined with clinical tumor biology and clinical correlates in a systems biology network. The DRP based on microRNA is used on certain products where the DRP based on messenger RNA is more broadly useable and more validated.

(Filing, 10-K, Eli Lilly, FEB 19, 2016, View Source [SID:1234509112])

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The period January to December 2015 and the fourth quarter 2015 in brief (Press release, Kancera, FEB 19, 2016, View Source [SID:1234511318]).

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· R&D expenses for the period amounted to SEK 20.4m (SEK 13.7m) of which the fourth quarter constituted SEK 8.3m (SEK 4.1m). Following EU’s approval of Kancera’s mid-term report for the A PARADISE project, the project’s revenues and expenses have been taken up which means that the reported R & D expenses and revenues for the period increased by SEK 4.8m. Thus, excluding the EU-project the R & D expenses for the period amounted to SEK 15.6m (SEK 13.7m), of which the fourth quarter constituted SEK 3.5m (SEK 4.1m).
· Operating income for the period amounted to SEK -19.7m (SEK -16.1m) of which the fourth quarter constituted SEK -5.9m (SEK -5.1m).
· Income after financial items for the period amounted to SEK -19.6m (SEK -16.0m) of which the fourth quarter constituted SEK -5.9m (SEK -5.0m).
· Earnings per share for the period were SEK -0.19 (SEK -0.18) of which the fourth quarter constituted SEK -0.06 (SEK -0.05).
· Cash flow from operating activities for the period amounted to SEK -20.7m (SEK -19.1m) of which the fourth quarter constituted SEK -4.5m (SEK -7.5m).
· Equity as of December 31, 2015 amounted to SEK 21.9m (SEK 27.3m) or SEK 0.21 (SEK 0.28) per share. The equity/assets ratio as of December 31, 2015 was 80 percent (75 percent).
· Cash and cash equivalents as of December 31, 2015 amounted to SEK 15.6m (SEK 23.0m). Cash and cash equivalents exclude the contribution of SEK 2.8m paid by the EU in January 2016.

Significant events during the period

· Kancera reported that a second efficacy study of the drug candidate KAN0439834 has been completed in an animal model of an advanced stage of chronic lymphocytic leukemia characterized by a genetic change which makes the disease more difficult to treat. The results show that KAN0439834 reduces the number of ROR expressing leukemia cells in the lymphatic system (spleen) after 14 days of treatment. Further, Kancera reported that a second patent application EP15153394.0 has been filed covering small-molecule ROR inhibitors, including the drug candidate KAN0439834.
· Kancera reported that the patent WO 2011/079902 concerning monoclonal antibodies against ROR1 has been approved in China. Kancera has acquired partial rights to this patent from Bioinvent under an agreement that does not involve any financial burden for Kancera (except patent expenses) before revenues are generated. Kancera through the company’s co-founder Professor Håkan Mellstedt has been involved in the development of these antibodies. These antibodies have mainly been used to identify and validate new indications for a future ROR-inhibiting drug. Any further development of the ROR-targeted monoclonal antibodies for therapeutic purposes will only be done in a partnership that provides funding and access to expertise in development of antibody-based drugs.
· Kancera reported an operational update of the cancer projects ROR, PFKFB3, and HDAC6.

– The ROR project reported that Kancera’s candidate drug KAN0439834 is effective against both leukemic cells circulating in the blood and leukemic cells that have invaded the lymph nodes in humans.

– Recent studies of clinical samples from leukemia patients underscore that ROR inhibitors mainly target the white blood cells causing cancer while the healthy white blood cells, including T cells, are spared. These results are of significance for the possibility to combine ROR inhibitors with the new generation of immuno-stimulating cancer drugs that have been developed since the effect of those requires functional T-cells.

– A new generation of ROR inhibitors is being developed against solid tumors.

– The PFKFB3 project reported a new discovery showing that Kancera’s PFKFB3 inhibitor KAN0438757 kills cancer cells by preventing them to repair their DNA. The discovery indicates that KAN0438757 could be an efficient complement to radiation for the treatment of advanced cancer.

– The HDAC6 project reported that Kancera’s HDAC6 inhibitors counteract the migration of cancer-associated fibroblast cells and that an international patent application was filed in May.

· Kancera’s Annual General Meeting on May 28, 2015 decided to re-elect the current Board of Directors and auditor (Ernst & Young). The General Meeting also decided to authorize the Board, on one or more occasions until the next Annual General Meeting, to issue new shares. A new share issue may be made with or without preferential rights and against cash payment and / or in kind or set-off. The purpose of the authorization and the reason for the deviation from shareholders’ preferential rights is to enable the acquisition of capital for corporate acquisitions and the company’s operation. If the share issue is made against cash payment and without preferential rights for the shareholders, the number of shares issued may not exceed ten percent of the total number of shares outstanding at the time the authorization is exercised.
· Kancera announced that a new share issue, with the authorization of the Annual General Meeting in 2014, was closed on May 27, 2015. The issue comprised a maximum of 4,927,386 shares. In total 25,926,793 shares were signed, of which 4,644,304 with preferential rights (with the support of subscription rights) and 21,282,489 without preferential rights. The share issue was thus oversubscribed to about 500 percent. This issue raised Kancera AB approximately SEK 12.3m before issue costs.
· Kancera announced that the first subscription period for the exercise of the employee warrants was closed in June 2015. In total 450,246 new shares were signed giving Kancera SEK 1.7m before issue costs. There remain 2,349,754 warrants, of which 560,000 are held by Kancera to cover social security costs that are part of the employee warrants program.
· Kancera announced that the company’s HDAC6 project has been awarded a grant totaling SEK 2m from the Swedish innovation agency VINNOVA. The grant is directed to projects that can develop into new strong innovations in a range of common diseases, including cancer. The grant is paid on four occasions during the two-year project. The project will be implemented in collaboration with the Cancer Center Karolinska (CCK), and is also planned to involve Swedish companies such as SARomics Biostructures, MetaSafe and Adlego Biomedical.
· Kancera announced that the company has entered into an agreement with Acturum Life Science AB in order to evaluate and further develop the unique Fractalkine receptor antagonist AZD8797. Based on published research that supports that the Fractalkine receptor antagonist may have a central role in different cancer forms, Kancera will evaluate how efficiently the Fractalkine receptor antagonist AZD8797 may stop tumor growth and relieve severe cancer pain. The agreement with Acturum Life Science gives Kancera right to evaluate AZD8797 in preclinical studies and then to acquire the project. This agreement entails no expenses for Kancera apart from investments in the patent portfolio and in the scientific evaluation. If Kancera chooses to acquire the Fractalkine project, following the preclinical evaluation phase, the total payment to Acturum will consist of 6 million Kancera shares divided into three tranches, which are due at pre-defined success-milestones.
· Kancera provided an operational update on the ROR and Fractalkine projects:

– In the ROR project, Kancera reported that follow-up studies of the pharmaceutical properties of KAN0439834 show that they probably are better than previously assumed with respect to uptake and penetration of the substance to the cancer. The new studies indicate that dosing 2-3 times a day at 65-300 mg gives a concentration in the body that may be sufficient to exert an effect on solid tumors. Against this background, ROR inhibitors will be tested in animal models of solid tumors. It was further reported that ROR inhibitors have shown effect against leukemic cells from bone marrow which is a capacity wanted since the existing drugs are not sufficiently effective against cancer cells in the bone marrow.

– In the Fractalkine project, Kancera reported that a network of leading cancer and pain scientists that has been established that will evaluate the drug candidate KAN0440567 (AZD8797) in an advanced animal model closely resembling the human form of pancreatic cancer. Kancera has synthesized and quality controlled the salt form of the drug candidate that will be used in this study and has conducted a successful peroral dosing study in mice.

· Kancera provided an operational update on the PFKFB3 and HDAC6 projects as well as the EU-funded and epigenetically targeted anti-parasitic project A-PARADDISE:

– From the collaboration with Prof. Thomas Helleday, Kancera reported that Kancera’s PFKFB3 inhibitor significantly reduces the size of a tumor formed by aggressive human breast cancer cells (so-called triple negative breast cancer) transplanted in zebrafish. The results from the study support that Kancera’s PFKFB3 inhibitor is effective against these aggressive cancer cells if the substance reaches the tumor in sufficient concentration, which is easier to achieve in zebrafish than e.g. in mice.

– Kancera has developed several chemical families of potent and selective HDAC6 inhibitors based on a common scaffold, and Kancera reported the decision to withdraw the original patent application from 2014 in order to postpone the publication of the structures at least 12 months. This is done in order to prevent Kancera’s existing patent application to become an obstacle to a new patent application covering the recently developed HDAC6 inhibitors.

– Vinnova announced in June 2015 that Kancera has been awarded a grant to support the further development of HDAC6 inhibitors against cancer. The first part of the grant was paid in July. VINNOVA decided to bring forward the second payment (SEK 750, 000) to the HDAC6 project to December 2015.

– In February 2014 Kancera received an initial payment from the EU amounting to € 523,655 (about SEK 4.6m) for the execution of the A-PARADDISE project. The project has now delivered a midterm report which has been approved by the EU. This means that a second installment of the grant was paid to Kancera at year-end according to plan. This payment amounted to € 300,000 (about SEK 2.8m).

Significant events after the end of the reporting period

· Kancera has from the 1st of January 2016 extended the lease of the company’s laboratories within the Karolinska Science Park for three years through an agreement with Humlegården Fastigheter.
· Kancera has provided an update of the small molecule patent portfolio.

– A patent covering small molecule PFKFB3 inhibitors has been approved in the USA.

– A patent application covering new chemical series in the HDAC6 project has been filed.

– The patent application covering ROR inhibitors filed in February 2015 has been strengthened by adding examples of additional highly potent ROR inhibitors.

· Kancera reported that the company has developed a new series of ROR inhibitors that show improved pharmaceutical properties which will allow preclinical studies of their effect on e.g. solid tumors. These results have prompted Kancera to concentrate the investments in the ROR project to small molecule inhibitors and terminate the product development of a ROR-based vaccine. Furthermore, Kancera reported results from the Fractalkine project showing that KAN0440567 after oral administration to mice effectively blocks the function of the Fractalkine receptor.

Statement from the CEO

2016 began as usual with an intense biotech week in San Francisco where Kancera and most of the Pharmaceutical and Biotech industry gathered to discuss cooperation opportunities in individual meetings. During the week in San Francisco, Thomson Reuters also presented its retrospection of 2015 which was a strong year for the industry with more and larger acquisitions than ever and a strong interest in preclinical drug development projects. The generally high interest from major pharmaceutical and biotech companies to acquire pharmaceutical project continues, which is reflected partly in the increasing level of payment upon signature of the acquisition or licensing agreements and partly in increasing total price tags for pharmaceutical projects. Cancer, by virtue of the great medical need, continues to be the therapeutic area in which most agreements are reached (for more information, see the Market Outlook section).

In the third quarterly report in 2015, I described the challenge in the ROR-project to achieve a sufficiently high concentration of the drug candidate in the blood to enable studies of efficacy against more cancer diseases, in addition to chronic lymphocytic leukemia, such as solid tumors. During the fourth quarter we have succeeded to develop a new series of compounds in the ROR project that can be maintained in an active concentration in the blood for 10 hours in mice. This can be compared with the approximately 2.5 hours shown by Kancera’s first drug candidate KAN0439834 in the same type of measurement. This progress now provides us with new opportunities to test the effect of ROR inhibitors in several preclinical models of severe human cancers.

During the fourth quarter we have also been able to show that oral administration of the Fractalkine receptor antagonist KAN0440567 to mice effectively blocks the function of the Fractalkine receptor. This is a first step in the ongoing studies to examine the effect of this substance against cancer of the pancreas in a preclinical model of the disease.

Furthermore, in January we reported several reinforcements of Kancera’s portfolio of patents and patent applications, including a new application from the HDAC6 project, a granted patent from the PFKFB3 project and a completion of the international patent application from the ROR project including new substances showing up to 20 times higher effect against leukemia cells compared to Kancera’s first drug candidate.

Overall, we see progress in Kancera’s entire project portfolio which further strengthens the company’s competitiveness and business development efforts.

Thomas Olin

CEO Kancera

On February 19, 2016 Kancera reported that the company has developed a new series of ROR inhibitors that show improved pharmaceutical properties which will allow preclinical studies of their effect on e.g. solid tumors (Press release, Kancera, FEB 19, 2016, View Source [SID:1234511317]). These results have prompted Kancera to concentrate the investments in the ROR project to small molecule inhibitors and terminate the product development of a ROR-based vaccine. Furthermore, Kancera reported results from the Fractalkine project showing that KAN0440567 after oral administration to mice effectively blocks the function of the Fractalkine receptor in mice.

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During the fourth quarter 2015, the ROR project succeeded to develop a new series of compounds in the ROR project that can be maintained in an active concentration in the blood for 10 hours in mice. This can be compared with the approximately 2.5 hours shown by Kancera’s first drug candidate KAN0439834 in the same type of measurement. This progress now provides us with new opportunities to test the effect of ROR inhibitors in several preclinical models of severe human cancers.

Kancera’s evaluation of peptide sequences for vaccine development has shown that the selected ROR-peptides do not generate an immune response that corresponds to the effect achieved with Kancera’s small molecule inhibitors. Against this background, Kancera has now chosen to terminate the vaccine product development and bring back the vaccine project to academic research. Thus, Kancera will concentrate the ROR-project investments to the development of small molecule inhibitors.

During the fourth quarter 2015, in collaboration with Prof. Mia Phillipson, Uppsala University, Kancera has demonstrated that oral administration of the Fractalkine receptor antagonist KAN0440567 (also referred to as AZD8797) to mice, effectively blocks the function of the Fractalkine receptor. This is a first step in the ongoing studies to examine the effect of this substance against cancer of the pancreas in a preclinical model of the disease.

Further information on these results can be found in Kancera’s Interim Report for Q4, 2015, which is published today.

About the ROR project
ROR is a family of receptors, ROR1 and ROR2. The ROR receptors mediate signals for growth and survival. Originally ROR was linked to fetal development, but it is now known that they also contribute to cancer cell development and proliferation. Professor Håkan Mellstedt, Kancera´s co-founder and professor at the Karolinska Institute, and his colleagues have shown that Kancera´s ROR inhibitors have the ability to kill cells from tumors in pancreas and leukemia cells. Professor Mellstedt and his colleagues as well as independent researchers have shown that ROR is also active as a target in prostate, breast, skin and lung cancer.

Because ROR primarily generates a survival and growth signal to tumor cells but is inactive in healthy cells in adults, there are good prospects that a drug directed against ROR hit the tumor much harder than the surrounding healthy cells. Kancera and Professor Mellstedt have shown that inhibition of ROR leads to that cancer cells eliminate themselves by cellular suicide. Against this background, there are reasons to anticipate that a ROR-targeted drug is both safer and more effective than several chemotherapies currently used to treat cancer.

About the Fractalkine project
Fractalkine is an immune regulatory factor that sends signals via the CX3CR1 receptor, also called G-protein coupled receptor 13 (GPCR13). In the healthy individual, Fractalkine and its receptor regulate migration of immune cells from the blood capillary wall into areas where the immune system is needed. Animal studies show that Fractalkine and its receptor are not essential for survival and that important immune functions remain intact indicating that inhibition of the Fractalkine signaling by a drug probably will be tolerated without significant adverse effects. Fractalkine and its receptor have been linked to the growth and proliferation of pancreatic, breast and prostate cancer. Also, cancer cells that have the Fractalkine receptor on their surface migrate towards nerve ends that have Fractalkine on their surface. Thus, cancer cells are led to surround and apply pressure on nerves and thereby cancer pain may arise. Another proposed mechanism for how Fractalkine and its receptor affect the development of tumors is that they contribute to the transformation of the body’s macrophages from being a threat against the cancer (the M1 form) to supporting the cancer (the M2 form). This mechanism is also suggested as a predictive factor for responsiveness to the new immuno-oncology drugs that act through PD-1 and PD-L1 such as nivolumab, pembrolizumab and pidilizumab. During 2014 and 2015 studies have been published demonstrating that the absence of Fractalkine in tumor cells is a significant marker for how successful the immuno-oncology treatment is expected to be (see e.g. the publication in Nature on November 27, 2014, Vol. 515, pp 563). In the light of these observations, there are good reasons to further study if inhibition of the Fractalkine signaling with KAN0440567 (AZD8797) has the potential to increase the proportion of patients responding to the new immuno-oncology drugs that act through PD-1 and PD-L1.

On February 19, 2016, the U. S. Food and Drug Administration approved palbociclib (IBRANCE Capsules, Pfizer, Inc.) in combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
In February 2015, FDA granted accelerated approval for palbociclib in combination with letrozole for the treatment of HR-positive, HER2-negative advanced breast cancer as initial endocrine based therapy in postmenopausal women.

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Today’s approval is based on the demonstration of an improvement in progression – free survival (PFS) in an international, randomized, double-blind, parallel group, multicenter study comparing palbociclib plus fulvestrant to placebo plus fulvestrant. Women enrolled had HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression on or after prior adjuvant or metastatic endocrine therapy.

A total of 521 pre- and postmenopausal women were randomized (2:1) to either palbociclib plus fulvestrant or placebo plus fulvestrant until disease progression or unacceptable toxicity. Palbociclib was administered orally at a dose of 125 mg daily for 21 consecutive days followed by 7 days off treatment. Fulvestrant was administered intramuscularly at a dose of 500 mg on days 1, 15, 29 and once monthly thereafter. Pre- or perimenopausal women were enrolled in the study and received the LHRH agonist, goserelin, for at least 4 weeks prior to and for the study’s duration.

Among the 521 patients, 80% were postmenopausal, all patients had received prior systemic therapy, and 75% had received a previous chemotherapy regimen. Twenty-five percent had not received prior therapy for metastatic disease, 60% had visceral metastases, and 23% had bone only disease.

The major efficacy outcome measure was investigator-assessed PFS evaluated according to RECIST V1.1. The study demonstrated an improvement in PFS with a hazard ratio of 0.46 (95% CI: 0.36, 0.59; p<0.0001). The median PFS was 9.5 versus 4.6 months for patients treated in the palbociclib plus fulvestrant and placebo plus fulvestrant arms, respectively.

Safety data was evaluated in 345 patients who received palbociclib plus fulvestrant. The most common (greater than or equal to 10%) of grade 1-4 adverse reactions were neutropenia, leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache, diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash, decreased appetite, and pyrexia. The most common (greater than or equal to 5%) grade 3-4 adverse reactions were neutropenia (66%) and leukopenia (31%).

The most frequently reported serious adverse reactions in patients receiving palbociclib plus fulvestrant were infections, pyrexia, neutropenia, and pulmonary embolism). Dose reductions due to an adverse reaction of any grade occurred in 36% of patients and permanent discontinuation associated with an adverse reaction occurred in 6% of patients.

The recommended dose and schedule of palbociclib is 125 mg daily for 21 consecutive days followed by 7 days off treatment in combination with fulvestrant treatment. The dose and schedule of fulvestrant is 500 mg intramuscularly on days 1, 15, 29 and once monthly thereafter.

Palbociclib is being approved prior to the Prescription Drug User Fee Act (PDUFA) goal date of April 15, 2016. This application was granted Priority Review and Breakthrough Therapy Designation. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: View Source

Full prescribing information is available at:
View Source

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at View Source, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).