Xtandi (INN enzalutamide) Timeline

Revised February 14, 2022

Early 2000

UCLA claims work that led to the development of enzalutamide began at UCLA in early 2000.

2005

May 13, 2005.  Priority date for the three patents in the Xtandi Orange Book. Patents 7709517, 8183274 and 9126941 (hereinafter, the “Xtandi patents”).

August 12, 2005.  UCLA licenses Xtandi patents to Medivation. (Agreement)

2007

June 29, 2007.  Application to FDA for investigational new drug.

July 23, 2007.  Start date for 140-patient Phase 1 study (NCT00510718).

2009

October 26, 2009.  Medivation enters into a collaboration agreement with Astellas. (Agreement)

October 29, 2009.  Announcement of Medivation-Astellas collaboration agreement. (Press release)

“In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialize MDV3100. . . companies will jointly commercialize MDV3100 in the U.S. and Astellas will have responsibility for commercializing MDV3100 outside the U.S. Medivation received a $110 million up-front payment upon entering into the collaboration agreement, and is eligible to receive up to $335 million in development milestone payments (including a milestone payment triggered by initiation of the PREVAIL trial), up to $320 million in commercial milestone payments, 50% of profits on sales in the U.S., and tiered, double-digit royalties on sales outside the U.S.”

October 30, 2009.  ClinicalTrials.Gov start date of 1,199 patent pivotal AFFIRM trial (NCT00974311).

2011

September 15, 2011.  Primary completion date for AFFIRM trial.

2012

May 22, 2012.  Application submitted to the FDA for approval as a human drug product under section 505(b) of the FD&C Act.

August 31, 2012.  FDA approval of Xtandi (101 days from NDA application; 5 years and 2 months from IND; 7.3 years from patent priority date; less than 3 years from the start of the pivotal AFFIRM trial (NDA 203415)).

2015

December 18, 2015.  The FDA publishes a notice in the Federal Register regarding “Determination of Regulatory Review Period for Purposes of Patent Extension”; XTANDI. (80 FR 79047)

2016

January 14, 2016.  Knowledge Ecology International (KEI) and the Union for Affordable Cancer Treatment (UACT) submits a request to the National Institutes of Health (NIH) and Department of Defense (DoD) asking that they exercise their authority under the Bayh-Dole Act to authorize the generic production of enzalutamide, because of the high and discriminatory price of Xtandi in the United States. (Petition)

March 4, 2016.  UCLA press release on sale of royalty interest to Royalty Pharma. (Press Release)

“The research that began in the early 2000s and culminated in the creation of Xtandi . . . The transaction includes a cash payment of $1.14 billion and potential additional payments based on future Xtandi sales . . UCLA’s share of the proceeds were $520 million . . . researchers and Howard Hughes Medical Institute shared a royalty interest in worldwide net sales of Xtandi. UCLA owns 43.875 percent of the royalty interest.”

March 21, 2016.  11 public interest policy and advocacy organizations send a letter to the NIH supporting the KEI/UACT petition. (Letter)

April 22, 2016.  Biolyse Pharma writes Centers for Medicare and Medicaid Services Acting Administrator Andy Slavitt, offers to sell generic versions of enzalutamide to Medicare and other federal programs for $3 per pill. (Biolyse letter)

May 5, 2016. Medivation files SEC Form 10-Q, for quarterly period ended March 31, 2016, stating “In March 2016, the National Institutes of Health, or NIH, reiterated its continuing position that drug pricing does not meet the statutory requirements justifying use of its march-in authority. Subsequently, several members of Congress, including presidential candidate Bernie Sanders, requested that the U.S. Department of Health and Human Services and NIH hold public hearings to determine if we and our partner Astellas have not met the statutory requirement to make XTANDI available to U.S. residents on reasonable terms. While the government has yet to exercise its march-in rights in response to pricing pressures or shortage problems, it may do so in the future which would significantly negatively impact our ability to generate revenue from XTANDI.”

June 20, 2016.  The NIH rejects the original march-in/government use license petition. (Decision)

August 5, 2016.  The DoD followed suit, rejecting the march-in/government use license petition. (Decision)

August 22, 2016.  The New York Times reports that Pfizer had offered $14 billion to acquire Medivation.

August 30, 2016. Medivation Schedule 14D-9 filing with the SEC on the Pfizer tender offer. (filing).

September 28, 2016.  Pfizer completes the acquisition of Medivation for $14.3 billion. In SEC filings, Pfizer later said it valued the Medivation interest in Xtandi (the developed asset) at $8.7 billion).

September 28, 2016.  Biolyse Pharma asks HHS for an agreement to use the government’s worldwide license (under 35 U.S.C. § 202(c)(4)) to use the patents for enzalutamide, to manufacture and export an affordable version to South Africa and other countries with low per-capita incomes relative to the United States.

October 17, 2016.  56 patient, senior citizen, global health, development, social justice, and faith groups urged the United States government to use its rights in a federally funded patented invention pursuant to 35 U.S.C. § 202(c)(4), and accept the request by a Canadian generic drug manufacturer (Biolyse Pharma) to enter into an agreement to manufacture and export an affordable version of the taxpayer-funded prostate cancer drug enzalutamide to South Africa and other countries with low per-capita incomes relative to the United States. (Letter)

2017

April 29, 2017.  KEI and UACT appeal the NIH/Collins decision to HHS Secretary Price. (Appeal)

June 7, 2017.  The KEI/UACT appeal is rejected by Francis Collins. (Decision)

July 10, 2017.  Senate Armed Services Committee Report 115-125 on the NDAA includes a directive requiring the granting of a march-in if prices in the United States are higher than the median price of the seven countries with the largest GDP and at least half the U.S. per capita income for a licensed federally-owned medical invention. (Report, page 173)

September 2017.  US Navy veteran, Emily Leonard makes a public representation to the University of California’s Board of Regents on behalf of UAEM regarding the lack of affordability of Xtandi and the role of University of California, Los Angeles (UCLA). (Video)

2018

March 2018.  UAEM students launch a campaign asking UCLA and the Board of Regents of the University of California to end support for litigation in India to obtain patent protection for enzalutamide in order to block the supply of affordable generic versions.

May 1, 2018.  The Department of Commerce’s National Institute of Standards and Technology (NIST) publishes “Request for Information Regarding Federal Technology Transfer Authorities and Process,” in the Federal Register. (83 FR 19052). The notice describes as a challenge, “industry concern about the scope of required government use licenses and whether and under what circumstances the government may exercise march-in rights.”

September 2018.  UAEM delivers 3,500 signatures on a petition to the University of California, Los Angeles, (UCLA) President Janet Napolitano, urging the university to drop its patent claim filed in the Indian High Court for enzalutamide, a prostate cancer medicine. (IP-Watch report)

December 6, 2018.  NIST publishes a draft green paper on its “Return on Investment Initiative.” The report includes extensive discussion of government use and march-in rights, and recommends significant restrictions on both. (NIST Special Publication 1234). Lead author is Walter G. Copan, the Director of NIST since 2017 under Trump. Before leading NIST, Copan worked advising companies and universities on intellectual property strategies. After returning to the private sector at the end of Trump’s presidency, he became a Vice President for research at Colorado School of Mines and co-founder of the Center for Strategic and International Studies (CSIS) program on innovation and intellectual property, where he campaigns against government use and march-in rights.

2019

February 4, 2019.  Two prostate cancer patients, Clare Melvin Love, a retired computer programer and Vietnam veteran, and David Reed, a computer scientist, submitted a request to the Army asking them to use march-in or royalty free rights in enzalutamide patents. (Petition)

April 24, 2019.  NIST publishes the final version of the green paper on “Return on Investment Initiative.” (Report) The report includes extensive discussion of government use and march-in rights, and recommends significant restrictions on both.

July 16, 2019.  The FDA grants Eugia Pharma (subsequently acquired by Aurobindo Pharma) tentative approval to market enzalutamide. Abbreviated New Drug Application (ANDA): 211465

2020

September 12, 2020.  President Trump issues Executive Order 13948, titled “Lowering Drug Prices by Putting America First.” (Executive Order, 85 FR 59649)

It is the policy of the United States that the Medicare program should not pay more for costly Part B or Part D prescription drugs or biological products than the most-favored-nation price. (b) The ‘‘most-favored-nation price’’ shall mean the lowest price, after adjusting for volume and differences in national gross domestic product, for a pharmaceutical product that the drug manufacturer sells in a member country of the Organisation for Economic Co-operation and Development (OECD) that has a comparable per-capita gross domestic product.

2021

January 4, 2021.  NIST publishes a request for comments on changes in regulations related to the Bayh-Dole Act governing “Rights to Federally Funded Inventions and Licensing of Government Owned Invention.” (86 FR 35). The most controversial proposal by NIST was to “Clarify § 401.6 to include a provision that march-in rights shall not be exercised by an agency exclusively on the basis of business decisions of a contractor regarding the pricing of commercial goods and services arising from the practical application of the invention.” NIST receives an extraordinary 81,772 comments, including more than eighty thousand in opposition to the effort to eliminate pricing as a basis for a march in. (The docket: NIST-2021-2021-0001. Selected comments here)

April 12, 2021.  Prostate cancer patient Robert Sachs files a petition with the Department of Defense, asking to join the outstanding Love and Reed petition on Xtandi. (Petition)

May 14, 2021.  Actavis Laboratories receives ANDA approval for enzalutamide. (FDA Letter)

July 9, 2021.  President Biden issues Executive Order 14036, “Promoting Competition in the American Economy.” This Executive Order called upon NIST to withdraw the proposed limitation on the use of march-in rights on the basis of the pricing of goods and services. (Executive Order)

(r) The Secretary of Commerce shall:
. . .
(ii) acting through the Director of NIST, consistent with the policies set forth in section 1 of this order, consider not finalizing any provisions on march-in rights and product pricing in the proposed rule “Rights to Federally Funded Inventions and Licensing of Government Owned Inventions,” 86 Fed. Reg. 35 (Jan. 4, 2021);

July 26, 2021.  Representative Seth Moulton writes to DoD asking that a hearing be held on the Xtandi petition.

September 9, 2021.  HHS Secretary Xavier Becerra forwards a report to the White House on measures to address drug prices, titled “Comprehensive Plan for Addressing High Drug Prices: A Report in Response to the Executive Order on Competition in the American Economy,” (U.S. Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation, September 9, 2021). (Report)

March-In Rights and Government Use . . . The federal government may grant a license to use the intellectual property arising from government funding without the permission of the rights-holder under certain circumstances, including when “action is necessary to alleviate health and safety needs which are not reasonably satisfied” or when the benefits of the patented product are not “available to the public on reasonable terms . . . HHS, NIH, and other agencies have been petitioned to take action under these provisions, and HHS will continue to give such petitions due consideration.* HHS will also engage other government agencies to address barriers to accessing government-funded inventions as emphasized in the Competition Executive Order, which directs the Director of the National Institute for Standards and Technology to consider not finalizing any provisions on march-in rights and product pricing in the proposed rule, “Rights to Federally Funded Inventions and Licensing of Government Owned Inventions.”
* Another provision, 28 U.S.C. § 1498, allows the federal government to “use or manufacture” technologies protected under current U.S. patents, while giving the patent owner “recovery of his reasonable and entire compensation for such use and manufacture”

October 1, 2021.  The World Health Organization (WHO) includes enzalutamide on its Essential Medicines List (EML). (Release)

October 1, 2021.  The Medicines Patent Pool (MPP) publishes a press release calling for voluntary licensing of three new medicines on the WHO EML including enzalutamide. (Release)

November 17, 2021.  In a case involving Paxlovid, a drug for the treatment of COVID-19, Pfizer signs a contract with the U.S. Army, agreeing to provide the United States with a Most Favored Nation price, defined as the lowest price for the G7 countries plus Switzerland.

November 18, 2021.  Robert Sachs and Clare Love petition the Secretary of Health and Human Services Xavier Becerra asking that HHS grant march-in rights for the patents on the prostate cancer drug enzalutamide. (Petition)

December 13, 2021.  Eric Sawyer petitions the Department of Health and Human Services, asking to join the outstanding march-in petition. (Letter)

December 23, 2021.  Dr. Tara A. Schwetz, Acting Principal Deputy Director of the NIH, emails acknowledgement of the November 18th request and states that Secretary Becerra had assigned review of the request to the NIH.

December 23, 2021.  Robert Sachs replies to Dr. Schwetz, restating the request for a hearing on the issue, and asking whom at the NIH would review the petition, as well as the expected timeline of the process.

2022

January 10, 2022.  Dr. Schwetz replies to Robert Sachs stating that, “The petition will be reviewed by the NIH Office of the Director, and the review will likely require approximately a month” and asserting that the issue of whether a hearing should be held would follow any decision by the NIH to move forward with the march-in request.

January 14, 2022.  Universities Allied for Essential Medicines submits a request to join the Xtandi march-in petition. (Letter)

January 19, 2022.  Public Citizen submitted a letter asking HHS Secretary Becerra and NIH Acting Principal Deputy Director Schwetz to support the march-in request for Xtandi. (Letter)

January 25, 2022.  Clare Love submits a KEI memorandum supporting the petition to Secretary Becerra and the NIH. (Memorandum)

February 2, 2022.  A group of Harvard Medical School faculty writes to Secretary Becerra supporting the petition. (Letter)

February 3, 2022. Xtandi petitioners send a letter to HHS and NIH highlighting that the US government-Pfizer Paxlovid contract contains a reference pricing clause, wherein the US government is entitled to the lowest cost for Paxlovid of the G7 countries + Switzerland, and asking the NIH to use the same or a similar standard to evaluate the Xtandi petition. (Letter)

February 8, 2022. A dozen members of the House of Representatives, led by Representatives DeFazio and Doggett, sent a letter to HHS Secretary Becerra urging him to follow through with Biden Administration’s commitment to lowering exorbitant prescription drug costs, and to move forward with the Xtandi request. (Letter, Press Release)

February 9, 2022. A.B. Engelberg, J. Avorn, and A.S. Kesselheim, publish “A New Way to Contain Unaffordable Medication Costs — Exercising the Government’s Existing Rights.” (NEJM, DOI: 10.1056/NEJMp2117102). The article encourages the federal government to use those rights to enable generic competition of enzalutamide.

February 9, 2022. Astellas publishes a “Quote and Statement on the Bayh Dole Act and Xtandi. (Statement)

February 9, 2022. Astellas releases a statement on the Bayh-Dole Act and the petition to exercise march-in and government use rights in the prostate cancer drug Xtandi. (Statement)

February 15, 2022. KEI publishes comments regarding the Astellas claims concerning public and private sector contributions to the development of Xtandi. (Comment)

February 17, 2022. Senators Elizabeth Warren (D-MA) and Angus King (I-ME), and Representative Lloyd Doggett (D-TX) sent a letter to HHS Secretary Becerra urging him to move forward with the Xtandi march-in petition and to consider using the government’s license under Section 202(c)(4) of the Bayh-Dole Act to authorize generic production for government programs. (Letter)

February 23, 2022. Seventeen organizations and nine individuals signed on to a letter of support for the Xtandi request sent to Secretary Becerra and Acting Director Tabak. (Letter)

February 23, 2022. UAEM sends letter to HHS and NIH, asking to recuse the NIH technology transfer official, Mark Rohrbaugh, from having any decision-making role in the response to the 2022 petition to march-in and exercise other rights in the patents on the prostate cancer drug Xtandi. (Letter)

February 23, 2022. Love, Sachs and Sawyer submit letter to HHS and NIH, with rebuttal of Astellas February 9, 2022 statement. (Letter)