On November 27, 2019 Incyte (Nasdaq:INCY) reported that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review its New Drug Application (NDA) for pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, as a treatment for patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements (Press release, Incyte, NOV 27, 2019, View Source [SID1234551749]).

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The NDA submission is based on data from the FIGHT-202 study evaluating pemigatinib as a treatment for patients with previously treated, locally advanced or metastatic cholangiocarcinoma. Study results, recently presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress, demonstrated that in patients harboring FGFR2 fusions or rearrangements (Cohort A), pemigatinib monotherapy resulted in an overall response rate (ORR) of 36 percent (primary endpoint), and median duration of response (DOR) of 7.5 months (secondary endpoint) with a median follow-up of 15 months. Adverse events were manageable and consistent with the mechanism of action of pemigatinib.

"There is a significant need for new therapies for patients with cholangiocarcinoma, who have limited treatment options beyond first-line chemotherapy and often face a poor prognosis," said Peter Langmuir, M.D., Group Vice President, Targeted Therapeutics, Incyte. "We are very pleased that the FDA has accepted our NDA for Priority Review which we believe represents an important step toward providing the first treatment option for patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements. We intend to work closely with the FDA to bring this innovative targeted therapy to patients suffering from this devastating disease as soon as possible."

The FDA grants Priority Review to medicines that may offer a major advance in treatment where none currently exists. This designation shortens the review period to eight months compared to 12 months for Standard Review. The Prescription Drug User Fee Act (PDUFA) target action date is May 30, 2020.

Cholangiocarcinoma is a rare cancer that forms in the bile duct. It is classified based on its origin: intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. Patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor.1,2 The incidence of cholangiocarcinoma varies regionally and ranges between 0.3 – 3.4 per 100,000 in North America and Europe.1 FGFR2 fusions or rearrangements occur almost exclusively in iCCA, where they are observed in 10-16 percent of patients.3-5

About FIGHT-202

The FIGHT-202 Phase 2, open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of pemigatinib – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥ 18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg pemigatinib orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 is overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR in Cohorts B, A plus B, and C; progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety in all cohorts.

For more information about FIGHT-202, visit View Source

About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating safety and efficacy of pemigatinib therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating pemigatinib in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type. FIGHT-205 is a Phase 2 study investigating pemigatinib plus pembrolizumab combination therapy and pemigatinib monotherapy in patients with previously untreated, metastatic or unresectable bladder cancer harboring FGFR3 mutations or fusions/rearrangements who are not eligible to receive cisplatin. FIGHT-302 is a recently initiated Phase 3 study investigating pemigatinib as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About FGFR and Pemigatinib

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating fusions, rearrangements, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers.

Pemigatinib is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations. The U.S. Food and Drug Administration (FDA) has granted pemigatinib Breakthrough Therapy designation for the treatment of previously treated, advanced/metastatic or unresectable FGFR2 translocated cholangiocarcinoma. The FDA’s Breakthrough Therapy designation is designed to expedite the development and review of drugs for serious conditions that have shown encouraging early clinical results and may demonstrate substantial improvements over available medicines. Additionally, the FDA granted pemigatinib Orphan Drug designation for the treatment of cholangiocarcinoma, a designation granted to investigational compounds intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people.

On November 27, 2019 Medivir AB reported that Interim Result January – September 2019 (Press release, Medivir, NOV 27, 2019, View Source;interim-report-january—september-2019-300966014.html [SID1234551768]).

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Financial summary

Net turnover amounted to SEK 1.7 (3.0) million.

The loss before interest, tax, depreciation and amortization (EBITDA) totaled SEK -22.0 (-66,9) million. Basic and diluted earnings per share amounted to SEK -0.95 (-2.93) SEK and SEK -0.95 (-2.93) respectively.
Cash flow from operating activities amounted to SEK -31.8 (-78.4) million.
Liquid assets and short-term investments totaled SEK 158.5 (357.1) million at the period end.
January – September

Financial summary

Net turnover amounted to SEK 7.3 (10.3) million.
The loss before interest, tax, depreciation and amortization (EBITDA) totaled SEK -88.6 (-229.8) million. Basic and diluted earnings per share amounted to SEK -3.76 (-9.88) and SEK -3.76 (-9.88) respectively.
Cash flow from operating activities amounted to SEK -125.3 (-248.1) million.
Liquid assets and short-term investments totaled SEK 158.5 (357.1) million at the period end.
Significant events after the quarter

The first patient was included in a phase I study in which the safety and tolerability of a combination of birinapant and radiotherapy are evaluated in patients with recurrent epithelial cancer in the head and neck region. The study is sponsored and funded as part of the National Cancer Institute’s Cancer Treatment Evaluation Program (CTEP).
The first milestone-payment for the candidate drug MIV-701 in veterinary medicine was received in October.
Preclinical data showing that in addition to its direct effect on cancer cells, MIV-818 also modulates the anti-tumor immune response, presented at the AACR (Free AACR Whitepaper)-NCI-EORTC conference in Boston.
The ninth and final liver cancer patient was included in the phase Ia study with MIV-818. Based on safety and tolerability as well as pharmacokinetics and positive biomarker data, it was decided to initiate the phase Ib portion of the study.
Conference call for investors, analysts and the media

The Interim Report January – September 2019 will be presented by Medivir’s President & CEO, Uli Hacksell.

Time: Wednesday, November 27, 2019, at 14.00 (CET).

On November 27, 2019 InDex Pharmaceuticals Holding AB (publ) reported that Interim result January – September 2019 (Press release, InDex Pharmaceuticals, NOV 27, 2019, View Source;september-2019-300965959.html [SID1234551769]).

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Period July – September 2019

Revenues amounted to SEK 0.0 (0.0) million
Operating result amounted to SEK -27.2 (-15.1) million
Result after tax amounted to SEK -27.2 (-15.1) million, corresponding to SEK -0.39 per share (-0.24) before and after dilution
Cash flow from operating activities amounted to SEK -19.1 (-16.1) million
Period January – September 2019

Revenues amounted to SEK 0.1 (0.1) million
Operating result amounted to SEK -62.1 (-59.9) million
Result after tax amounted to SEK -62.2 (-59.9) million, corresponding to SEK -0.90 per share (-0.96) before and after dilution
Cash flow from operating activities amounted to SEK -51.6 (-58.6) million
Cash and cash equivalents at the end of the period amounted to SEK 117.6 (66.4) million
Number of employees at the end of the period was 7 (7)
Number of shares at the end of the period was 82,537,530
All comparative amounts in brackets refer to the outcome during the corresponding period 2018.

Significant events during July – September 2019

The phase IIb study CONDUCT met the primary endpoint.
InDex updated the list of shareholders on the homepage with information as of August 30, 2019.
InDex completed a directed share issue of approximately SEK 140 million.
InDex announced notice of an extraordinary general meeting.
Significant events after the reporting period

InDex held an extraordinary general meeting, which resolved to approve the Board’s resolution on a new issue of shares with deviation from the shareholders’ preferential rights.
InDex updated the list of shareholders on the homepage with information as of October 18, 2019.
CEO statement
On August 27, we had the great pleasure of reporting successful top line results in the phase IIb study CONDUCT with cobitolimod. The study met the primary endpoint with a competitive efficacy and superior safety profile. Now it is full speed ahead towards phase III.

The CONDUCT study was an exploratory study to find the best dose to move forward in development, and the study clearly showed that the highest dose was the most effective. As in previous studies, cobitolimod was well tolerated at all dose levels and no differences in the safety profile were observed compared to placebo. The study thus met the objectives that we set up before the start of the study.

The efficacy was within the expected range and is comparable to what has been reported for the drugs that are currently on the market for moderate to severe ulcerative colitis and the new substances that are in phase III right now. Something that really differentiates cobitolimod from its competitors is the superior safety profile. Both the approved drugs and those currently being tested in phase III are associated with serious side effects. With an outstanding combination of efficacy and safety, cobitolimod is set to take a leading position within the field.

An additional advantage of cobitolimod that stands out compared to the competitors is the new and unique mechanism of action. Many patients with moderate to severe ulcerative colitis do not respond to current therapies, and there is more and more talk about combining several drugs to optimise the efficacy for the patients. With its unique mechanism of action and safety profile, cobitolimod is better suited than competing products for such an approach.

DIRECTED SHARE ISSUE TAKES COBITOLIMOD TO PHASE III
With the successful CONDUCT results, we completed a directed share issue on September 19 of SEK 140 million to Swedish and international investors, including reputable, new investors such as the Fourth Swedish National Pension Fund and existing shareholders such as Industrifonden and Bengt Julander (through Linc AB). We received great interest from investors with sector expertise, also internationally, during the roadshow that preceded the transaction, and we did not have to offer any discount, which is otherwise the standard in directed share issues.

The proceeds of the share issue are primarily intended to prepare cobitolimod for phase III, which is the final stage of development before applying for market approval. We had already before the CONDUCT results planned a long list of phase III preparatory activities that we launched as soon as we saw the positive outcome of the study. We are now analysing the full data set with the intention of publishing complete study results in a scientific journal and presenting them at upcoming medical conferences. We have initiated contacts with the European and American regulatory authorities, EMA and the FDA, to discuss phase III design. We are planning market research with physicians and payers. We have started the process of choosing a contract research organisation (CRO). We have ordered study drug and have started the preclinical safety studies required for phase III. With the current timeline, we should have enough information to finalise the design of the phase III program in the second quarter of 2020 and be ready to enrol the first patient in the second half of 2020.

NEW FINANCIALLY STRONG INVESTORS STRENGTHEN THE SHAREHOLDER BASE
The ownership in InDex has changed significantly during the quarter. Former major shareholder NeoMed, which owned 10 percent of the shares in InDex as of June 30, started selling its holdings on the stock exchange in July and continued to sell off large volumes in connection with the results being presented at the end of August. Bengt Julander is now the company’s third largest shareholder with 10 percent of the shares and the Fourth Swedish National Pension Fund the fourth largest with 7 percent. SEB Venture Capital and Industrifonden are still the largest shareholders with approximately 15 percent each. We are very pleased that the list of shareholders has been strengthened with additional long-term and financially strong investors.

NEW POSSIBILITIES FOR PHASE III DESIGN CREATES STRATEGIC FLEXIBILITY
Traditionally, phase III programs in moderate to severe ulcerative colitis have included approximately 1,000 patients, which required significant amounts of capital. Over the past six months, we have seen clear signals that the regulatory authorities have opened up for innovative and smaller phase III programs. This shift by the authorities lets us plan for a phase III program that InDex can manage on its own. A key is to carry out the studies sequentially and not in parallel as traditionally done. You can then read out study by study along the way, which lowers the risk as the studies are completed and allows stepwise financing of the program. This without having to take longer time to complete than a traditional design. With the strengthened shareholder base and the positive feedback we received from institutional investors in connection with the directed share issue, we see the opportunity to finance the further development of cobitolimod and thereby create additional value.

From a strategic and negotiation perspective, it is a great strength to be autonomous and be able to control the timing and circumstances for potential future partnerships. As we prepare for phase III on our own, we continue our business development work to present the positive CONDUCT results and development plans to companies that have shown interest in cobitolimod. The possibility of a less extensive phase III program also widens the universe of potential partners to include regional and speciality pharma companies. Also the large global companies can appreciate the benefits of an innovative phase III program. Even if they do not have capital constraints, there is competition for patients and smaller studies means a faster way to market.

With positive phase IIb results, new capital, a strong shareholder base and strategic flexibility, we look forward to 2020 and the further development of cobitolimod and InDex as a company.

On November 27, 2019 Pfizer Inc. reported investors and the general public to listen to a webcast of a discussion with Mikael Dolsten, Chief Scientific Officer and President, Worldwide Research, Development and Medical, and Michael Vincent, Senior Vice President and Chief Scientific Officer, Inflammation and Immunology, at the Evercore ISI 2nd Annual HealthCONx Conference on Wednesday, December 4, 2019 at 10:15 a.m. Eastern Standard Time (Press release, Pfizer, NOV 27, 2019, View Source [SID1234551751]).

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To listen to the webcast, visit our web site at www.pfizer.com/investors. Information on accessing and pre-registering for the webcast will be available at www.pfizer.com/investors beginning today.

Visitors will be able to listen to an archived copy of the webcast at www.pfizer.com/investors.

On November 27, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that an anticancer agent/anti-PD-L1 (Programmed Death-Ligand 1) monoclonal antibody Tecentriq Intravenous Infusion 840 mg [generic name: atezolizumab (recombinant)] has been listed on the National Health Insurance (NHI) reimbursement price list and launched (Press release, Chugai, NOV 27, 2019, View Source [SID1234551735]). Tecentriq 840 mg is an optimal formulation to be dosed every two weeks for the treatment of PD-L1-positive hormone receptor-negative and HER2-negative inoperable or recurrent breast cancer. This additional indication and dosage were approved on September 20, 2019.

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"Immune checkpoint inhibitor has been changing the treatment paradigm among various types of cancers in recent years. We are very pleased that we can now deliver Tecentriq to patients with PD-L1 positive TNBC as the first approved immune checkpoint inhibitor in the breast cancer field," said Dr. Osamu Okuda, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "TNBC is an aggressive and rapidly progressing disease with limited treatment options, and there are high unmet medical needs. We would engage in providing information, aiming at contributing to patients thorough offering this cancer immunotherapy-based treatment for TNBC as a new treatment option."

Tecentriq is an immune checkpoint inhibitor targeting PD-L1 which is a protein expressed on tumor cells and tumor-infiltrating immune cells. PD-L1 blocks T-cell activity by binding with PD-1 and B7.1 receptors on T-cell surface. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells and boost immune response against cancer cells. The efficacy and safety of Tecentriq were investigated in the phase III IMpassion130 study.

As a top pharmaceutical company in the field of oncology in Japan, Chugai is committed to contribute to patients and medical professionals by offering Tecentriq as a new treatment option and accordingly, to improve access to medications and appropriate use.

About the IMpassion130 study
The IMpassion130 study is a Phase III, multicenter, randomized, double-blind study evaluating the efficacy, safety and pharmacokinetics of Tecentriq plus nab-paclitaxel (albumin-bound) compared with nab-paclitaxel (albumin-bound) in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer. The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) and OS in the ITT population and in the PD-L1-positive population.

[Reference]
Chugai Obtains Approval for Additional Indication and Formulation for Tecentriq in PD-L1-Positive Triple Negative Breast Cancer (Press release issued on September 20, 2019)
View Source

Termination of free offering of Tecentriq 840 mg prior to the listing on the NHI reimbursement price list
Under the system for healthcare services combining insurance-covered and non-covered services provided by the Ministry of Health, Labour and Welfare, Chugai has been offering Tecentriq 840 mg for free to respond to requests for emergency use from patients with PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer with very limited treatment options since its approval dated on September 20, 2019. Chugai announced the termination of free offering of Tecentriq 840 mg with the listing on the NHI reimbursement price list as of today.

Prescribing Information

Product name Tecentriq Intravenous Infusion 840 mg
Generic name atezolizumab (genetical recombination)
Indications Tecentriq Intravenous Infusion 840 mg
PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer
Dosage and administration
In case of patients with PD-L1-positive, hormone receptor-negative and HER2-negative inoperable or metastatic breast cancer.
The usual adult dosage is 840 mg atezolizumab (genetical recombination) in combination with nab-paclitaxel (albumin-bound) administered by intravenous infusion over 60 minutes once every 2 weeks. If the initial infusion is well tolerated, subsequent infusions can be delivered over 30 minutes.
Drug price Tecentriq Intravenous Infusion 840 mg JPY 448,853/vial
Conditions for approval
A risk management plan should be created and appropriately implemented.
About Triple-Negative Breast Cancer
In Japan, 86,500 women (2018 predicted value) are estimated to be afflicted with breast cancer each year. 14,800 women in Japan (2018 predicted value) die as a result of the disease.1) Triple-negative breast cancer accounts for 15% of all breast cancer cases and, is more common in women under the age of 50, compared with other forms of breast cancer.2-4) Triple-negative breast cancer is defined by the lack of expression of hormone receptors (estrogen and progesterone receptors) and the overexpression of human epidermal growth factor receptor 2 (HER2). In general, triple-negative breast cancer has a high tumor-proliferative capacity and shorter overall survival, compared with other forms of breast cancer.3, 5)

Trademarks used or mentioned in this release are protected by law.

Sources

Cancer Registry and Statistics. Cancer Information Service, National Cancer Center, Japan. [Internet; cited October, 2019] Available from: View Source

Yao H et al. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget. 2017;8(1):1913–1924.
BreastCancer.org. What is Triple-Negative Breast Cancer? [Internet; October, 2019] Available from: View Source
Cancer Treatment Centers of America. Triple negative breast cancer risk factors. [Internet; cited October, 2019]
View Source
Pal SK et al. Triple negative breast cancer: unmet medical needs. Breast Cancer Res Treat. 2011;125(3):627-636.