Timeline of key events in the development of Campath

Waldmann, under the mentorship of Alan Munro, launches research to understand the mechanism behind immune tolerance. 1973-01-01T00:00:00+0000Waldmann joins the Laboratory of Molecular Biology to learn how to produce monoclonal antibodies.1978-01-01T00:00:00+0000Work begins on the development of an anti-T-cell monoclonal antibody that can fix human complement to be used as a tool to prevent graft-versus-host disease in patients receiving bone marrow transplants. 1979-01-01T00:00:00+0000Referred to as Campath-1 (CAMbridge Pathology) family of antibodies, these are the first set of monoclonal antibodies against human lymphocytes derived from a rat. 1980-01-01T00:00:00+0000Waldmann is granted a programme grant to investigate the immunobiology of bone marrow transplantation.1980-01-01T00:00:00+0000The man treated is suffering from non-Hodgkin's lymphoma. While unable to prevent the death of the patient, the trial shows Campath-1M to be effective at depleting T-cells and well-tolerated.1982-01-01T00:00:00+0000The woman's bone marrow recovers after treatment. Treatment is halted after it is shown that the woman's bone marrow has been reconstituted by her own stem cells rather than those of her donor. 1982-01-01T00:00:00+0000Testing is undertaken as part of a collaboration between Waldmann and Shimon Slavin at Haddasah Hospital, Jerusalem. Results are promising but two patients reject their transplants, so Waldmann and his team take a break from testing.1983-01-01T00:00:00+0000The aim is to generate Campath monoclonal antibodies that can be infused directly into patients. 1983-01-01T00:00:00+0000G. Hale et al, 'Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement', Blood, 62, (1983), 873-82.1983-10-25T00:00:00+0000The patient is being cared for by Martin Dyer and Frank Hayhoe. He is suffering from chronic lymphocytic leukaemia (CLL). Although the patient died shortly after treatment from his underlying disease, the result from the testing is promising. 1985-01-01T00:00:00+0000Campath-1G is seen as a possible means to reduce immunosuppressive drugs. Fears about the toxicity of the drug prevent work going any further. 1985-01-01T00:00:00+0000Wellcome Biotech gain the rights to develop Campath for a number of diseases including CLL.1985-01-01T00:00:00+0000The company develops the mechanism for the large-scale manufacture of Campath-1H. 1985-01-01T00:00:00+0000Campath-1G is humanised, resulting in Campath-1H. It is accomplished with technology developed by Greg Winter.1988-01-01T00:00:00+0000The patient is a 69 year old woman suffering from non-Hodgkin's lymphoma. The drug dramatically improves her health. 1988-01-01T00:00:00+0000Patients show marked improvements with the drug.1988-11-01T00:00:00+0000The aim of the centre is to facilitate the production of Campath and other monoclonal antibodies for clinical testing.1990-09-01T00:00:00+0000The research is undertaken by John Isaacs in collaboration with Brian Hazelman at Addenbrooke's Hospital.1991-01-01T00:00:00+0000Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).1991-01-01T00:00:00+0000The drug dramatically improves the patient's condition.1991-01-01T00:00:00+0000BTG starts negotiations to license Campath to a commercial partner.1993-01-01T00:00:00+0000Waldmann takes up a position in the William Dunn School of Pathology, 1994-01-01T00:00:00+0000The move is prompted by Waldmann's Oxford University appointment.1994-01-01T00:00:00+0000Coles joins as a doctoral student.1994-01-01T00:00:00+0000This is due to the company being reabsorbed into its parent company and disappointing results from trials conducted with Campath-1H for RA.1994-10-01T00:00:00+0000Roy Calne, Peter Friend and Waldman's team launch a small trial with 31 kidney transplant patients to see if Campath-1H can help in reducing immunosuppressant drugs. 1997-01-01T00:00:00+0000Wellcome transfers its manufacturing expertise on Campath to Boehringer Ingelheim. 1997-01-01T00:00:00+0000LeukoSite is granted the license by BTG to develop Campath-1H for CLL and other disease indications.1997-04-01T00:00:00+0000The two companies enter a drug development partnership. 1997-05-01T00:00:00+0000Leukosite raises US$17 million.1997-08-01T00:00:00+0000Analysis of 29 MS patients given MS indicate Campath-1H might be more effective if given earlier in the course of the disease.1998-01-01T00:00:00+0000The trial is to test Campath-1H for treating B-CLL. 1998-04-01T00:00:00+0000Results collected from 93 patients indicates Campath-1H to be a promising treatment for B-CLL.1999-06-01T00:00:00+0000The alliance is for the marketing of Campath-1H.1999-08-01T00:00:00+0000Millennium Pharmaceuticals pays US$750 million in stock.1999-12-01T00:00:00+0000An application is submitted. 1999-12-01T00:00:00+0000Known as the CAM 307 trial, the study compareds Campath-1H with chlorambucil, a standard first-line treatment for the disease.2001-01-01T00:00:00+0000The approval is for Campath-1H to be used as a third-line treatment of B-CLL.2001-05-01T00:00:00+0000Campath-1H is approved for the European market as a third-line treatment of B-CLL. 2001-07-01T00:00:00+0000Results from 58 MS patients indicate Campath-1H more effective in those who are less advanced in their disease.2002-01-01T00:00:00+0000This comes about after a meeting between Jeff Bulchalter, chief executive officer of Ilex Oncology and Compston.2002-01-01T00:00:00+0000Known as CAMMS223, this randomised control trial, which compares Campath-1H with interferon beta-1a, indicates Campath-1H is an effective treatment for MS.2002-01-01T00:00:00+0000Genzyme pays US1 billion for the acquisition.2004-04-01T00:00:00+0000The resulting company is Bayer Schering Pharma.2006-01-01T00:00:00+0000Positive results reported from 1,779 patients.2007-01-01T00:00:00+00002007-09-01T00:00:00+00002007-12-01T00:00:00+0000Genzyme gains the worldwide rights to Campath-1H from Bayer Schering Pharma.2009-01-01T00:00:00+0000Campath-1H shown to help lower the amount of immunosuppressant drugs taken by organ transplant patients. 2011-01-01T00:00:00+0000Granted by European regulatory authorities.2013-09-17T00:00:00+0000Alemtuzumab was originally developed by Herman Waldmann as a laboratory tool to investigate immune tolerance. It soon became the first humanised monoclonal antibody drug. Initially alemtuzumab proved effective for helping prevent graft-versus host disease in transplant patients. It subsequently went on to be approved as a treatment for leukaemia and then many years later it was shown to be effective against multiple sclerosis. 2013-09-17T00:00:00+0000US patients start campaign to reverse FDA decision2013-12-27T00:00:00+0000Known as Lemtrada, alemtuzumab was originally developed by Herman Waldmann as a tool for the investigation of immune tolerance. The drug, which is the oldest numanised monoclonal antibod,y is now used for many different diseases. Alastair Compston was the clinician who pioneered the use of the antibody for the treatment of multiple sclerosis. The first patient treated for multiple sclerosis with the drug happened in 1991. For more on the long history of the drug see http://whatisbiotechnology.org/index.php/exhibitions/campath2014-11-25T00:00:00+0000
Date Event People Places
1973Herman Waldmannn joins the Department of Pathology, Cambridge University.WaldmannCambridge University
1978 - 1979Waldmann takes a sabbatical with Cesar Milstein.WaldmannLaboratory of Molecular Biology
1979Waldmann is joined in his work by Stephen Cobbold, Geoff Hale, Alan Munro, Don Metcalfe, Suzanne Watt and Hoang Trang.Waldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge University
1980First monoclonal antibodies developed against T-cells which can also activate human complement.Waldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge University
1980Waldmann gains MRC funding.WaldmannCambridge University
1982The first patient is treated with Campath-1M.Waldmann, Swirsky, HayhoeCambridge University
1982Campath-1M is given to a patient with aplastic anaemia undergoing a bone marrow transplantWaldmann, Hows, Gordon SmithHammersmith Hospital
1983 - 1984Campath-1M is used in 11 leukaemia patients undergoing BMTs.Waldmann, SlavinHaddasah Hospital
1983 - 1985Efforts turn to generating IG Campath monoclonal antibodies.Waldmann, Hale, CobboldCambridge University
October 1983Publication of experiments indicating Campath-1 (alemtuzumab) monoclonal antibody activates complement and eliminate T-cellsWaldmann, Cobbold, Hale, Metcalfe. Watt, TrangCambridge University
1985Campath-1G is tested in the first patient.Waldmann, Hayhoe, DyerCambridge University
1985Campath-1G is explored on a small scale for the management of organ transplants by Roy Calne, a British transplant surgeon based at Addenbrooke's hospitalWaldmann, CalneCambridge University
1985Wellcome Biotech licenses the rights to commercially develop Campath.Wellcome Biotech, BTG
1985 - 1994Wellcome Biotech invests GBP 50 million in Campath.Wellcome Biotech
1988Campath-1H is created - the first clinically useful humanised monoclonal antibody.Winter, Waldmann, Reichmann, ClarkCambridge University, Laboratory of Molecular Biology
1988Campath-1H is tested in the first humanWaldmann, Hale, Dyer, HayhoeCambridge University
November 1988Martin Lockwood, a clinician at Addenbrooke's Hospital, begins testing Campath-1H in patients with vasculitis.Lockwood, Hale, WaldmannCambridge University
1 Sep 1990The Therapeutic Antibody Centre (TAC) opens in the Regional Transfusion Centre at Addenbrooke's Hospital.Waldmann, HaleCambridge University
1991Campath-1H begins to be tested in patients with rheumatoid arthritis (RA)Isaacs, Hazleman, Hale, WaldmannCambridge University
1991Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).Waldmann, Hale, CompstonCambridge University
1991The first MS patient is given Campath-1HWaldmann, hale, CompstonCambridge University
1993The rights to Campath are assigned to the British Technology Group (BTG).WaldmannCambridge University
1 Jan 1994Waldmann moves to Oxford University.WaldmannOxford University
1994The TAC relocates to Oxford.Hale, WaldmannOxford University
1994Alasdair Coles joins Compston's teamColesCambridge University
October 1994Wellcome Biotech abandons development of Campath-1H.Wellcome Biotech
1997Small scale tests launched with Campath-1H for organ transplant patients.Waldmann, Calne, FriendCambridge University
1997LeukoSite enters a manufacturing agreement for Campath-1H with Boehringer Ingelheim.Leukosite, Boehringer Ingelheim
April 1997Christopher Mirabelli, Chief Executive Officer of LeukoSite, agrees to take over the commercial development of Campath-1H.MirabelliLeukoSite
May 1997LeukoSite partners with Ilex Oncology.LeukoSite, Ilex Oncology
1 Aug 1997Leukosite makes its first initial public offering.Leukosite
1998Analysis of 29 MS patients given MS indicate Campath-1H might be more effective if given earlier in the course of the disease.Compston, Coles, Waldmann, HaleCambridge University
1 Apr 1998Leukosite and Ilex Oncology launch their first joint clinical trial of Campath-1H.Leukosite, Ilex Oncology
1 Jun 1999Results collected from 93 patients indicates Campath-1H to be a promising treatment for B-CLL.LeukoSite, Ilex Oncology
August 1999LeukoSite and Ilex Oncology partner with Schering AG.Leukosite, Ilex Oncology, Schering AG
1 Dec 1999Millennium Pharmaceuticals acquires LeukoSite.Millennium Pharmaceuticals, Leukosite
1 Dec 1999Regulatory approval is sought for Campath-1H for the treatment of B-CLL.Millennium Pharmaceuticals, Ilex Oncology
2001 - 2004Trial to establish efficacy of Campath-1H as first-line treatment for B-CLL.Genzyme
1 May 2001FDA approved Campath-1H 
1 Jul 2001European approval granted for Campath-1H 
2002Results from 58 MS patients indicate Campath-1H more effective in those who are less advanced in their disease.Compston, ColesCambridge University
2002Ilex Oncology agrees to raise funds to sponsor clinical trials for Campath-1H in MS patients.Compston, BuchalterIlex Oncology, Cambridge University
2002 - 2004Phase II trial tests Campath-1H for relapsing-remitting MS.Compston, ColesCambridge University, Ilex Oncology
1 Apr 2004Genzyme acquires Ilex Oncology.Genzyme, Ilex Oncology
2006Schering AG merges with BayerBayer, Schering AG
2007 - 2011Two phase III randomised control trials conducted with Campath-1H in patients with early MSCompston, ColesCambridge University, Ilex Oncology, Genzyme
September 2007FDA approved Campath-1H as first-line treatment for B-CLL 
December 2007Campath-1H granted European regulatory approval as first-line treatment for B-CLL. 
2009Genzyme buys rights to Campath-1H.Bayer Schering Pharma, Genzyme
2011Positive results from trials using Campath-1H for organ transplant patientsWaldmann, CalneCambridge University
September 2013Campath-1H gains marketing approval for the treatment of MS.Waldmann, Compston, ColesCambridge University
17 Sep 2013European Commission approved Alemtuzumab (Lemtrada) for MS treatmentCompston, Coles, WaldmannCambridge University, Sanofi
December 2013FDA rejected approval of Lembrada for MS treatmentSanofi
25 Nov 2014FDA approved alemtizumab for relapsing MS who failed to respond to alternative treatmentsWaldmann, CompstonAddenbrookes Hospital, Sanofi

1973

Herman Waldmannn joins the Department of Pathology, Cambridge University.

1978 - 1979

Waldmann takes a sabbatical with Cesar Milstein.

1979

Waldmann is joined in his work by Stephen Cobbold, Geoff Hale, Alan Munro, Don Metcalfe, Suzanne Watt and Hoang Trang.

1980

First monoclonal antibodies developed against T-cells which can also activate human complement.

1980

Waldmann gains MRC funding.

1982

The first patient is treated with Campath-1M.

1982

Campath-1M is given to a patient with aplastic anaemia undergoing a bone marrow transplant

1983 - 1984

Campath-1M is used in 11 leukaemia patients undergoing BMTs.

1983 - 1985

Efforts turn to generating IG Campath monoclonal antibodies.

Oct 1983

Publication of experiments indicating Campath-1 (alemtuzumab) monoclonal antibody activates complement and eliminate T-cells

1985

Campath-1G is tested in the first patient.

1985

Campath-1G is explored on a small scale for the management of organ transplants by Roy Calne, a British transplant surgeon based at Addenbrooke's hospital

1985

Wellcome Biotech licenses the rights to commercially develop Campath.

1985 - 1994

Wellcome Biotech invests GBP 50 million in Campath.

1988

Campath-1H is created - the first clinically useful humanised monoclonal antibody.

1988

Campath-1H is tested in the first human

Nov 1988

Martin Lockwood, a clinician at Addenbrooke's Hospital, begins testing Campath-1H in patients with vasculitis.

Nov 1988

The Therapeutic Antibody Centre (TAC) opens in the Regional Transfusion Centre at Addenbrooke's Hospital.

1991

Campath-1H begins to be tested in patients with rheumatoid arthritis (RA)

1991

Herman Waldmann and Alastair Compston begin a collaboration to test Campath-1H for treating multiple sclerosis (MS).

1991

The first MS patient is given Campath-1H

1993

The rights to Campath are assigned to the British Technology Group (BTG).

1993

Waldmann moves to Oxford University.

1994

The TAC relocates to Oxford.

1994

Alasdair Coles joins Compston's team

Oct 1994

Wellcome Biotech abandons development of Campath-1H.

1997

Small scale tests launched with Campath-1H for organ transplant patients.

1997

LeukoSite enters a manufacturing agreement for Campath-1H with Boehringer Ingelheim.

Apr 1997

Christopher Mirabelli, Chief Executive Officer of LeukoSite, agrees to take over the commercial development of Campath-1H.

May 1997

LeukoSite partners with Ilex Oncology.

May 1997

Leukosite makes its first initial public offering.

1998

Analysis of 29 MS patients given MS indicate Campath-1H might be more effective if given earlier in the course of the disease.

1998

Leukosite and Ilex Oncology launch their first joint clinical trial of Campath-1H.

1998

Results collected from 93 patients indicates Campath-1H to be a promising treatment for B-CLL.

Aug 1999

LeukoSite and Ilex Oncology partner with Schering AG.

Aug 1999

Millennium Pharmaceuticals acquires LeukoSite.

Aug 1999

Regulatory approval is sought for Campath-1H for the treatment of B-CLL.

2001 - 2004

Trial to establish efficacy of Campath-1H as first-line treatment for B-CLL.

2001

FDA approved Campath-1H

2001

European approval granted for Campath-1H

2002

Results from 58 MS patients indicate Campath-1H more effective in those who are less advanced in their disease.

2002

Ilex Oncology agrees to raise funds to sponsor clinical trials for Campath-1H in MS patients.

2002 - 2004

Phase II trial tests Campath-1H for relapsing-remitting MS.

2002

Genzyme acquires Ilex Oncology.

2006

Schering AG merges with Bayer

2007 - 2011

Two phase III randomised control trials conducted with Campath-1H in patients with early MS

Sep 2007

FDA approved Campath-1H as first-line treatment for B-CLL

Dec 2007

Campath-1H granted European regulatory approval as first-line treatment for B-CLL.

2009

Genzyme buys rights to Campath-1H.

2011

Positive results from trials using Campath-1H for organ transplant patients

Sep 2013

Campath-1H gains marketing approval for the treatment of MS.

17 Sep 2013

European Commission approved Alemtuzumab (Lemtrada) for MS treatment

Dec 2013

FDA rejected approval of Lembrada for MS treatment

25 Nov 2014

FDA approved alemtizumab for relapsing MS who failed to respond to alternative treatments